VEGFR/PDGFR Dual Kinase Inhibitor X-82 and Everolimus for Treating Patients With Pancreatic Neuroendocrine Tumors

A Phase I/II Study of X-82, an Oral Anti-VEGFR Tyrosine Kinase Inhibitor, With Everolimus for Patients With Pancreatic Neuroendocrine Tumors

Status

Terminated

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01784861

Enrollment

Registered

2013-02-06

Start date

2013-05-03

Completion date

2020-08-19

Last updated

2021-07-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Adenocarcinoma, Pancreatic Neoplasms

Brief summary

This study is to evaluate the combination of an investigational drug X-82 with everolimus in the treatment of pancreatic neuroendocrine tumors.

Interventions

DRUGX-82

DRUGEverolimus

Study design

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

Phase I and PK Expansion Cohort Inclusion Criteria * Phase I Patients: Histologic documentation of a solid malignancy and has exhausted available standard medical treatments or has no standard treatments currently available. This includes primary brain tumors. * PK Expansion Patients: Histologic documentation of locally unresectable or metastatic renal cell carcinoma not currently amenable to surgery, radiation, or other therapy with curative intent. * Measurable or nonmeasurable disease per RECIST 1.1 criteria. * ECOG performance status of 0-1 * At least 18 years of age. * Normal bone marrow and organ function as defined below: * Granulocytes ≥ 1,500/mcL * Platelets ≥ 100,000/mcL * Hemoglobin ≥9 g/dL * Creatinine ≤ 1.5 x ULN * Bilirubin ≤ 1.5 x ULN * AST and ALT ≤ 2.5 x ULN (≤ 5 x ULN if liver metastases are present) * Urine protein ≤ 1+ OR urine protein to creatinine ratio ≤ 1; if UPC ratio is \> 1 on urinalysis, then 24-hour urine collection for protein must be obtained and level must be \< 1,000 mg for patient enrollment. * QTcF \< 450 ms. * Normal LVEF. * Recovery from any major or minor surgeries. * Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. * Ability to swallow and retain oral medication. * Able to understand and willing to sign written informed consent document. Phase II Inclusion Criteria * Histologic documentation of well differentiated or moderately differentiated locally unresectable or metastatic pancreatic neuroendocrine tumor from either a primary or metastatic site with documented disease progression ≤ 12 months prior to enrollment whose disease is not currently amenable to surgery, radiation, or other modality therapy with curative intent. If different histologic classification schemes are used, equivalent histologic classifications (for example grade 1, low grade, or intermediate grade) are allowed. There must be histologic documentation of a pancreatic primary site or clinical evidence of a pancreatic neuroendocrine primary tumor as determined by the treating physician. Documentation from a metastatic site is sufficient if there is clinical evidence of a pancreatic primary site. In the case of discordant pathology, patient eligibility will be determined by the PI after review of available records. Patients with neuroendocrine tumors (e.g., gastrinoma, VIPoma) in whom a pancreatic or peripancreatic primary site is strongly suspected are also eligible. * Evidence of measurable disease per RECIST 1.1. Measurable disease is defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 2 cm with conventional techniques or as ≥ 1 cm with spiral CT scan. * There is no limit on the number of prior chemotherapy regimens allowed. Any prior treatment (with the exception of lanreotide or octreotide) must be completed at least 4 weeks prior to initiation of treatment. * Prior treatment with embolization or ablative therapies is allowed if measurable disease remains outside of the treated area or if there is definite progression of the treated lesions. There is no limit on the number of prior procedures. * ECOG performance status of 0-1 * At least 18 years of age. * Normal bone marrow and organ function as defined below: * Granulocytes ≥ 1,500/mcL * Platelets ≥ 100,000/mcL * Hemoglobin ≥9 g/dL * Creatinine ≤ 1.5 x ULN * Bilirubin ≤ 1.5 x ULN * ALT and AST ≤ 2.5 x ULN (≤ 5 x ULN if liver metastases are present) * Urine protein ≤ 1+ OR urine protein to creatinine ratio ≤ 1; if UPC ratio is \> 1 on urinalysis, then 24-hour urine collection for protein must be obtained and level must be \< 1,000 mg for patient enrollment. * QTcF \< 450 ms. * Normal LVEF. * Patients with fasting serum cholesterol \> 300 mg/dL OR \> 7.75 mmol/L AND fasting triglycerides \> 2.5 x ULN should initiate lipid lowering medications. * Recovery from any major or minor surgeries. Patient must be 4 weeks post-major surgery and 2 weeks post-minor surgery. * Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. * Ability to swallow and retain oral medication. * Able to understand and willing to sign written informed consent document.

Exclusion criteria

Phase I and PK Expansion Cohort

Design outcomes

Primary

Measure	Time frame	Description
Objective Response Rate (Complete Response + Partial Response) - Phase II	Through completion of treatment (estimated to be 12 months)	Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Number of Participants With Dose Limiting Toxicities - Phase I	Completion of 1st cycle for all patients in Phase I portion of study (completed in approximately 20 months)	Tolerability of X-82 in combination with everolimus will be determined by NCI Common Terminology Criteria for Adverse Events (CTCAE version 4.0)
Overall Toxicities - Phase I	30 days after completion of treatment (estimated to be 13 months)	-Toxicities will be graded by the NCI Common Terminology Criteria for Adverse Events (CTCAE version 4.0)
Recommended Phase II Dose of X-82	Completion of 1st cycle for all patients in Phase I portion of study (completed in approximately 20 months)	—

Secondary

Measure	Time frame	Description
Disease Stabilization Rate - Phase II	Through completion of treatment (estimated to be 12 months)	* Disease stabilization rate is defined as the proportion of patients achieving a best overall response of complete response, partial response, or stable disease. * Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. * Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. * Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits.
Progression Free Survival (PFS) - Phase II	Up to 3 years	* PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. * Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.
Overall Survival - Phase II	Up to 3 years	Start of the treatment until death.
Number of Participants With Toxicity - Phase II	Through 30 days after completion of treatment (estimated to be 13 months)	Toxicity will be graded by NCI Common Terminology Criteria for Adverse Events (CTCAE version 4.0)

Countries

United States

Participant flow

Participants by arm

Arm	Count
Phase I Dose Level 0: X-82 + Everolimus * X-82 100 mg by mouth once daily * Everolimus 10mg by mouth once daily for each cycle * Everolimus and X-82 should be taken at the same time every day * 28 days =1 cycle	3
Phase I Dose Level 1: X-82 + Everolimus * X-82 150 mg by mouth once daily * Everolimus 10mg by mouth once daily for each cycle * Everolimus and X-82 should be taken at the same time every day * 28 days =1 cycle	3
Phase I Dose Level 2: X-82 + Everolimus * X-82 200 mg by mouth once daily * Everolimus 10mg by mouth once daily for each cycle * Everolimus and X-82 should be taken at the same time every day * 28 days =1 cycle	4
Phase I Dose Level 3: X-82 + Everolimus * X-82 300 mg by mouth once daily * Everolimus 10mg by mouth once daily for each cycle * Everolimus and X-82 should be taken at the same time every day * 28 days =1 cycle	8
Phase I Dose Level 4: X-82 + Everolimus * Everolimus 10mg by mouth once daily for each cycle MUST BE TAKEN FIRST * X-82 400 mg by mouth once daily 2 HOURS AFTER everolimus dose * 28 days =1 cycle X-82 Everolimus	3
Phase II: X-82 + Everolimus * X-82 (dose determined by Phase I portion to be 300 mg) mg by mouth once daily * Everolimus 10mg by mouth once daily for each cycle * 28 days =1 cycle	2
Total	23

Withdrawals & dropouts

Period	Reason	FG002	FG003	FG004	FG005
Overall Study	Adverse Event	1	2	1	0
Overall Study	Physician Decision	0	2	0	1
Overall Study	Withdrawal by Subject	0	1	0	0

Baseline characteristics

Characteristic	Phase I Dose Level 0: X-82 + Everolimus	Total	Phase II: X-82 + Everolimus	Phase I Dose Level 4: X-82 + Everolimus	Phase I Dose Level 3: X-82 + Everolimus	Phase I Dose Level 2: X-82 + Everolimus	Phase I Dose Level 1: X-82 + Everolimus
Age, Continuous	71 years	59 years	64.5 years	59 years	53 years	53 years	61 years
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants	19 Participants	1 Participants	2 Participants	8 Participants	4 Participants	2 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants	4 Participants	1 Participants	1 Participants	0 Participants	0 Participants	1 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	2 Participants	6 Participants	0 Participants	1 Participants	0 Participants	1 Participants	2 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	1 Participants	16 Participants	2 Participants	1 Participants	8 Participants	3 Participants	1 Participants
Region of Enrollment United States	3 participants	23 participants	2 participants	3 participants	8 participants	4 participants	3 participants
Sex: Female, Male Female	1 Participants	11 Participants	0 Participants	2 Participants	2 Participants	3 Participants	3 Participants
Sex: Female, Male Male	2 Participants	12 Participants	2 Participants	1 Participants	6 Participants	1 Participants	0 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk
deaths Total, all-cause mortality	3 / 3	3 / 3	4 / 4	5 / 8	2 / 3	2 / 2
other Total, other adverse events	3 / 3	3 / 3	4 / 4	8 / 8	3 / 3	2 / 2
serious Total, serious adverse events	2 / 3	2 / 3	0 / 4	2 / 8	2 / 3	2 / 2

Outcome results

Primary

Number of Participants With Dose Limiting Toxicities - Phase I

Tolerability of X-82 in combination with everolimus will be determined by NCI Common Terminology Criteria for Adverse Events (CTCAE version 4.0)

Time frame: Completion of 1st cycle for all patients in Phase I portion of study (completed in approximately 20 months)

Population: -1 participant in Phase I Dose Level 2 was not evaluable for this outcome measure because they received less than one cycle of treatment. 1 participant in Phase I Dose Level 3 was not evaluable for this outcome measure because they received less than one cycle of treatment. 1 participant in Phase I Dose Level 3 was not evaluable for this outcome measure because they didn't receive any treatment.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Phase I Dose Level 0: X-82 + Everolimus	Number of Participants With Dose Limiting Toxicities - Phase I	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Number of Participants With Dose Limiting Toxicities - Phase I	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Number of Participants With Dose Limiting Toxicities - Phase I	0 Participants
Phase I Dose Level 3: X-82 + Everolimus	Number of Participants With Dose Limiting Toxicities - Phase I	1 Participants
Phase I Dose Level 4: X-82 + Everolimus	Number of Participants With Dose Limiting Toxicities - Phase I	0 Participants

Primary

Objective Response Rate (Complete Response + Partial Response) - Phase II

Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

Time frame: Through completion of treatment (estimated to be 12 months)

Population: Phase I participants are not evaluable for this outcome measure. One participant in the Phase II portion of the study was not evaluable because the treating physician removed the participant from the treatment prior to receiving the end of cycle 3 imaging.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Phase II: X-82 + Everolimus	Objective Response Rate (Complete Response + Partial Response) - Phase II	0 Participants

Primary

Overall Toxicities - Phase I

-Toxicities will be graded by the NCI Common Terminology Criteria for Adverse Events (CTCAE version 4.0)

Time frame: 30 days after completion of treatment (estimated to be 13 months)

Population: Phase II is zero analyzed because this outcome measure is for Phase I participants only.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Sinusitis	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Headache	1 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Pain to extremity	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Dry mouth	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Hiccups	1 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Hearing impaired	1 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Skin hypopigmentation	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Pancreas infection	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Dyspepsia	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Weight loss	1 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Confusion	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Epistaxis	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Alkaline phosphatase increased	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Abdominal pain	1 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Myalgia	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Flatulence	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Anorexia	1 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Tremor	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Lung infection	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Hemorrhoids	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Aphasia	1 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Stroke	1 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Intra-abdominal hemorrhage	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Testicular pain	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Sore throat	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Mood swings	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Depression	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Loss of taste	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Dehydration	1 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Taste changes	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Urinary tract infection	1 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Blood bilirubin increased	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Hypertriglyceridemia	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Mucositis oral	2 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Rash maculo-papular	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Hypernatremia	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Dizziness	1 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Thromboembolic event	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Nausea	1 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Hypoxia	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Sepsis	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Insomnia	1 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Colonic fistula	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Rectal fissure	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Hypophosphatemia	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Hair color changes	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Peritoneal infection	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Skin thinning	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Creatinine increased	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Stomach pain	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Bruising	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Vomiting	1 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Arthralgia	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Mesenteric ischemia	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Pleural effusion	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Night sweats	1 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Chills	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Trigeminal nerve disorder	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Hypertension	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Diarrhea	2 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Libido decreased	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Edema face	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Urinary frequency	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Rash acneiform	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Anemia	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Back pain	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Edema limbs	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Abdominal distension	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Diabetic ketoacidosis	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Nasal congestion	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Intraperitoneal bleeding	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Fatigue	1 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Hypovolemia	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Fever	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Peripheral vision/depth perception impairment	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Pain	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Anxiety	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Alopecia	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Constipation	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Neutrophil count decreased	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Cold sores	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Flank pain	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Cough	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Upper respiratory infection	1 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Dysphagia	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Elevated lactate dehydrogenase total	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Pruritis	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Dysgeusia	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Hot flashes	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Hematuria	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Oral thrush	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Slow wound healing	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Platelet count decreased	0 Participants
Phase I Dose Level 0: X-82 + Everolimus	Overall Toxicities - Phase I	Dyspnea	1 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Hypoxia	1 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Peritoneal infection	1 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Dyspnea	1 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Dysgeusia	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Hypertension	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Sinusitis	1 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Mesenteric ischemia	1 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Upper respiratory infection	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Epistaxis	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Myalgia	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Hot flashes	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Bruising	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Tremor	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Slow wound healing	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Hiccups	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Alkaline phosphatase increased	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Hair color changes	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Skin thinning	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Blood bilirubin increased	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Stroke	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Creatinine increased	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Fever	1 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Neutrophil count decreased	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Abdominal distension	1 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Trigeminal nerve disorder	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Skin hypopigmentation	1 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Platelet count decreased	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Hypovolemia	1 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Testicular pain	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Weight loss	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Sepsis	1 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Abdominal pain	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Anorexia	1 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Rash maculo-papular	1 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Dehydration	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Diabetic ketoacidosis	1 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Hypernatremia	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Hypophosphatemia	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Colonic fistula	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Hypertriglyceridemia	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Rash acneiform	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Arthralgia	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Aphasia	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Back pain	1 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Constipation	1 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Flank pain	1 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Anxiety	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Hematuria	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Pruritis	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Diarrhea	2 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Pain to extremity	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Pancreas infection	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Dry mouth	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Headache	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Sore throat	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Dyspepsia	1 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Confusion	1 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Urinary frequency	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Lung infection	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Flatulence	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Anemia	1 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Hemorrhoids	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Hearing impaired	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Intra-abdominal hemorrhage	1 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Loss of taste	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Depression	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Mood swings	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Thromboembolic event	1 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Mucositis oral	2 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Alopecia	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Nausea	1 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Dizziness	1 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Insomnia	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Rectal fissure	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Taste changes	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Pleural effusion	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Night sweats	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Stomach pain	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Vomiting	1 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Chills	1 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Nasal congestion	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Edema face	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Libido decreased	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Intraperitoneal bleeding	1 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Edema limbs	1 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Pain	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Fatigue	2 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Dysphagia	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Cold sores	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Cough	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Elevated lactate dehydrogenase total	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Urinary tract infection	0 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Oral thrush	2 Participants
Phase I Dose Level 1: X-82 + Everolimus	Overall Toxicities - Phase I	Peripheral vision/depth perception impairment	1 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Myalgia	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Pain to extremity	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Alopecia	1 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Aphasia	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Dizziness	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Anemia	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Mesenteric ischemia	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Trigeminal nerve disorder	1 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Sore throat	1 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Anxiety	1 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Confusion	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Depression	1 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Hearing impaired	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Nasal congestion	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Insomnia	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Libido decreased	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Hypoxia	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Cough	2 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Dyspnea	1 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Peripheral vision/depth perception impairment	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Epistaxis	1 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Hiccups	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Sepsis	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Stomach pain	1 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Abdominal distension	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Abdominal pain	1 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Hypovolemia	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Colonic fistula	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Pancreas infection	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Constipation	1 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Diarrhea	2 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Dry mouth	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Headache	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Lung infection	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Dyspepsia	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Pleural effusion	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Hemorrhoids	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Intra-abdominal hemorrhage	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Thromboembolic event	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Loss of taste	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Mucositis oral	2 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Mood swings	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Nausea	1 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Urinary frequency	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Night sweats	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Rectal fissure	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Vomiting	1 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Chills	1 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Intraperitoneal bleeding	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Edema face	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Hematuria	1 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Edema limbs	2 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Stroke	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Dysphagia	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Pain	2 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Cold sores	1 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Fatigue	3 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Elevated lactate dehydrogenase total	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Oral thrush	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Urinary tract infection	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Hypertension	1 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Peritoneal infection	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Blood bilirubin increased	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Hypertriglyceridemia	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Sinusitis	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Upper respiratory infection	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Hot flashes	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Bruising	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Tremor	1 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Slow wound healing	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Taste changes	1 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Skin thinning	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Alkaline phosphatase increased	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Creatinine increased	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Skin hypopigmentation	1 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Neutrophil count decreased	2 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Fever	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Platelet count decreased	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Weight loss	1 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Testicular pain	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Rash maculo-papular	2 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Anorexia	3 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Dehydration	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Hypernatremia	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Rash acneiform	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Hypophosphatemia	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Arthralgia	1 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Dysgeusia	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Back pain	1 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Hair color changes	1 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Pruritis	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Flank pain	1 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Diabetic ketoacidosis	0 Participants
Phase I Dose Level 2: X-82 + Everolimus	Overall Toxicities - Phase I	Flatulence	1 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Hypertension	1 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Hematuria	0 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Urinary frequency	2 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Hair color changes	0 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Hypovolemia	0 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Headache	3 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Mood swings	1 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Hemorrhoids	1 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Hypertriglyceridemia	2 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Taste changes	0 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Fever	2 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Hypernatremia	0 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Dysgeusia	2 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Anemia	1 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Hearing impaired	0 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Peripheral vision/depth perception impairment	0 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Abdominal distension	0 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Abdominal pain	5 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Colonic fistula	1 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Constipation	1 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Diarrhea	3 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Dry mouth	2 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Stomach pain	0 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Dyspepsia	0 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Flatulence	1 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Intra-abdominal hemorrhage	0 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Loss of taste	1 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Mucositis oral	4 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Nausea	3 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Rectal fissure	1 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Vomiting	2 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Chills	3 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Edema face	4 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Edema limbs	3 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Fatigue	5 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Pain	0 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Cold sores	0 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Elevated lactate dehydrogenase total	0 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Oral thrush	0 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Peritoneal infection	0 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Sinusitis	2 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Upper respiratory infection	0 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Urinary tract infection	0 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Bruising	2 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Slow wound healing	1 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Alkaline phosphatase increased	1 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Blood bilirubin increased	1 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Creatinine increased	1 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Neutrophil count decreased	3 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Platelet count decreased	4 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Weight loss	1 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Anorexia	3 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Dehydration	0 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Hypophosphatemia	1 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Arthralgia	0 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Back pain	2 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Flank pain	1 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Myalgia	1 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Pain to extremity	2 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Aphasia	0 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Dizziness	2 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Tremor	0 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Trigeminal nerve disorder	0 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Anxiety	0 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Confusion	1 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Depression	1 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Insomnia	3 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Libido decreased	1 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Testicular pain	1 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Cough	2 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Dyspnea	1 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Epistaxis	3 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Hiccups	0 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Hypoxia	0 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Nasal congestion	1 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Sore throat	0 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Alopecia	0 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Pruritis	2 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Rash acneiform	1 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Rash maculo-papular	2 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Skin hypopigmentation	0 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Skin thinning	1 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Hot flashes	0 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Dysphagia	0 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Intraperitoneal bleeding	0 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Night sweats	0 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Thromboembolic event	1 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Lung infection	0 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Pancreas infection	0 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Sepsis	0 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Diabetic ketoacidosis	0 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Stroke	0 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Pleural effusion	1 Participants
Phase I Dose Level 3: X-82 + Everolimus	Overall Toxicities - Phase I	Mesenteric ischemia	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Dysgeusia	1 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Alopecia	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Myalgia	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Flank pain	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Back pain	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Urinary frequency	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Pruritis	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Arthralgia	1 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Hypophosphatemia	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Hypertriglyceridemia	1 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Diabetic ketoacidosis	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Rash acneiform	1 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Dehydration	2 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Anorexia	3 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Weight loss	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Hypernatremia	1 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Rash maculo-papular	1 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Platelet count decreased	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Neutrophil count decreased	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Creatinine increased	1 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Taste changes	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Skin hypopigmentation	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Blood bilirubin increased	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Alkaline phosphatase increased	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Slow wound healing	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Hemorrhoids	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Skin thinning	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Bruising	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Urinary tract infection	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Upper respiratory infection	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Hematuria	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Hot flashes	1 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Sinusitis	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Peritoneal infection	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Oral thrush	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Elevated lactate dehydrogenase total	1 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Hypertension	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Cold sores	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Pain	1 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Fever	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Stroke	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Dysphagia	1 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Fatigue	2 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Hypovolemia	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Edema limbs	1 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Edema face	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Chills	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Constipation	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Intraperitoneal bleeding	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Vomiting	1 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Rectal fissure	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Nausea	1 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Mood swings	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Night sweats	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Mucositis oral	2 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Loss of taste	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Intra-abdominal hemorrhage	1 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Headache	1 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Thromboembolic event	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Flatulence	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Dyspepsia	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Stomach pain	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Mesenteric ischemia	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Lung infection	1 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Dry mouth	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Diarrhea	2 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Colonic fistula	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Pleural effusion	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Pancreas infection	1 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Abdominal pain	2 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Abdominal distension	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Peripheral vision/depth perception impairment	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Epistaxis	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Hair color changes	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Hiccups	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Dyspnea	1 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Cough	1 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Testicular pain	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Sepsis	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Hypoxia	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Libido decreased	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Insomnia	1 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Depression	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Hearing impaired	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Nasal congestion	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Confusion	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Anxiety	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Trigeminal nerve disorder	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Anemia	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Sore throat	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Tremor	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Dizziness	1 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Aphasia	0 Participants
Phase I Dose Level 4: X-82 + Everolimus	Overall Toxicities - Phase I	Pain to extremity	0 Participants

Primary

Recommended Phase II Dose of X-82

Time frame: Completion of 1st cycle for all patients in Phase I portion of study (completed in approximately 20 months)

Population: This was the recommended Phase II dose because there were concerns about the ability to maintain the 400 mg daily dosing level for multiple cycles without significant toxicity.

Arm	Measure	Value (NUMBER)
Phase I Dose Level 0: X-82 + Everolimus	Recommended Phase II Dose of X-82	300 mg

Secondary

Disease Stabilization Rate - Phase II

* Disease stabilization rate is defined as the proportion of patients achieving a best overall response of complete response, partial response, or stable disease. * Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. * Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. * Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits.

Time frame: Through completion of treatment (estimated to be 12 months)

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Phase II: X-82 + Everolimus	Disease Stabilization Rate - Phase II	1 Participants

Secondary

Number of Participants With Toxicity - Phase II

Toxicity will be graded by NCI Common Terminology Criteria for Adverse Events (CTCAE version 4.0)

Time frame: Through 30 days after completion of treatment (estimated to be 13 months)

Population: Phase I participants are not evaluable for this outcome measure.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Phase II: X-82 + Everolimus	Number of Participants With Toxicity - Phase II	Diarrhea	2 Participants
Phase II: X-82 + Everolimus	Number of Participants With Toxicity - Phase II	Mucositis oral	1 Participants
Phase II: X-82 + Everolimus	Number of Participants With Toxicity - Phase II	Nausea	1 Participants
Phase II: X-82 + Everolimus	Number of Participants With Toxicity - Phase II	Vomiting	1 Participants
Phase II: X-82 + Everolimus	Number of Participants With Toxicity - Phase II	Chest pain	1 Participants
Phase II: X-82 + Everolimus	Number of Participants With Toxicity - Phase II	Edema limbs	1 Participants
Phase II: X-82 + Everolimus	Number of Participants With Toxicity - Phase II	Hematoma	1 Participants
Phase II: X-82 + Everolimus	Number of Participants With Toxicity - Phase II	Mouth sores	1 Participants
Phase II: X-82 + Everolimus	Number of Participants With Toxicity - Phase II	Creatinine increased	1 Participants
Phase II: X-82 + Everolimus	Number of Participants With Toxicity - Phase II	Platelet count decreased	1 Participants
Phase II: X-82 + Everolimus	Number of Participants With Toxicity - Phase II	Hip pain	1 Participants
Phase II: X-82 + Everolimus	Number of Participants With Toxicity - Phase II	Leg cramps	1 Participants
Phase II: X-82 + Everolimus	Number of Participants With Toxicity - Phase II	Dizziness	1 Participants
Phase II: X-82 + Everolimus	Number of Participants With Toxicity - Phase II	Headache	1 Participants
Phase II: X-82 + Everolimus	Number of Participants With Toxicity - Phase II	Allergic rhinitis	1 Participants
Phase II: X-82 + Everolimus	Number of Participants With Toxicity - Phase II	Rash acneiform	1 Participants
Phase II: X-82 + Everolimus	Number of Participants With Toxicity - Phase II	Rash maculo-papular	1 Participants
Phase II: X-82 + Everolimus	Number of Participants With Toxicity - Phase II	Hypertension	1 Participants

Secondary

Overall Survival - Phase II

Start of the treatment until death.

Time frame: Up to 3 years

Population: Phase I participants are not evaluable for this outcome measure.

Arm	Measure	Value (MEDIAN)
Phase II: X-82 + Everolimus	Overall Survival - Phase II	115 days

Secondary

Progression Free Survival (PFS) - Phase II

* PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. * Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.

Time frame: Up to 3 years

Population: Phase I participants are not evaluable for this outcome measure.

Arm	Measure	Value (MEDIAN)
Phase II: X-82 + Everolimus	Progression Free Survival (PFS) - Phase II	183 days

Source: ClinicalTrials.gov · Data processed: Mar 1, 2026

VEGFR/PDGFR Dual Kinase Inhibitor X-82 and Everolimus for Treating Patients With Pancreatic Neuroendocrine Tumors

Conditions

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Number of Participants With Dose Limiting Toxicities - Phase I

Objective Response Rate (Complete Response + Partial Response) - Phase II

Overall Toxicities - Phase I

Recommended Phase II Dose of X-82

Disease Stabilization Rate - Phase II

Number of Participants With Toxicity - Phase II

Overall Survival - Phase II

Progression Free Survival (PFS) - Phase II