Advanced Soft Tissue Sarcoma, Locally Advanced Soft Tissue Sarcoma, Metastatic Soft Tissue Sarcoma
Conditions
Brief summary
This phase I/II trial studies the side effects and best dose of nab-sirolimus and how well it works when given together with pazopanib hydrochloride in treating participants with nonadipocytic soft tissue sarcomas that has spread to other places in the body (advanced). Nab-sirolimus and pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Detailed description
OUTLINE: This is a phase I, dose-escalation study of nanoparticle albumin-bound rapamycin followed by a phase II study. Participants receive nab-sirolimus intravenously (IV) on days 1 and 8 or day 1 only and pazopanib hydrochloride orally (PO) daily on days 1-21. Cycles repeat every 21 days until unequivocal clinical disease progression, unacceptable toxicity, or until in the opinion of the investigator the patient is no longer benefiting from therapy, or at the patient's discretion. After completion of study treatment, participants are followed up at 30 days, then every 12 weeks.
Interventions
Given IV
DRUGPazopanib hydrochloride
Given PO
Sponsors
Aadi Bioscience, Inc.
University of Washington
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects, \>= 18 years old, must have a histologically confirmed diagnosis of non-adipocytic soft tissue sarcoma (STS) that is either metastatic or locally advanced and for which curative therapy is not available, surgery is not a recommended option, and pazopanib treatment is indicated. * Subjects must have one or more measurable target lesions by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1, assessed via computed tomography (CT) scan or magnetic resonance imaging (MRI). * Clinical or radiological progression or failure due to toxicity on at least 1 prior regimen of systemic treatment for advanced disease. Subjects may not have received more than 4 prior lines of systemic therapy (no more than 2 prior therapies may be combination cytotoxic therapies). Neo-adjuvant/adjuvant/maintenance treatments are not included for this criterion. * Last dose of prior therapy must have been completed a minimum of 14 days prior to start of protocol therapy. All ongoing toxicities related to prior therapy must be resolved or grade 1 (except alopecia). \* NOTE: Toxicities from prior therapy that have resolved with sequelae (e.g. hypothyroidism) and are asymptomatic or well-controlled are not exclusionary. * Total bilirubin =\< upper limit of normal (ULN) mg/dL (Subjects with known Gilbert's syndrome and a total bilirubin =\< 3 mg/dl are permitted to enroll to phase 2/expansion phase only with sponsor-investigator approval). * Aspartate aminotransferase (AST) =\< 2.5 x ULN and alanine aminotransferase (ALT) =\< 2.5 x ULN. * Serum creatinine =\<1.5 x ULN (If serum creatinine is \> 1.5 mg/dL, calculated creatinine clearance \> 50 mL/min using the Cockcroft-Gault formula may be included). * Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L. * Platelet count \>= 100,000/mm\^3 (100 x 10\^9/L). * Hemoglobin \>= 9 g/dL. * Serum triglyceride =\< 300 mg/dL. * Serum cholesterol =\< 350 mg/dL. * Baseline cardiac left ventricular ejection fraction (LVEF) within institutional limits of normal (by echocardiogram or multigated acquisition \[MUGA\] study). * Baseline electrocardiogram with corrected QT (QTc) \< 480 millisecond (Bazett's). * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. * Male or non-pregnant and non-breast feeding female: * Females of child-bearing potential must agree to use highly effective contraception without interruption from initiation of therapy and while on study medication and have a negative serum pregnancy test (beta human chorionic gonadotropin \[beta-hCG\]) result at screening and agree to ongoing pregnancy testing during the course of the study, and at the end of study treatment. A highly effective method of contraception is defined as one that results in a low failure rate (that is, \< 1% per year), when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some intrauterine contraceptive devices, sexual abstinence, or a vasectomized partner. * Male patients must practice abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study. * Life expectancy of \> 3 months, as determined by the investigator. * Ability to understand and sign informed consent. * Willingness and ability to comply with scheduled visits, laboratory tests, and other study procedures.
Exclusion criteria
* Soft tissue sarcomas with biology or defined treatments for which pazopanib is not indicated, including adipocytic STS, gastrointestinal stromal tumors (GIST), or Kaposi's sarcoma. * Previously received an mTOR (mammalian target of rapamycin) inhibitor or angiogenesis inhibitor. * Known active uncontrolled or symptomatic central nervous system (CNS) metastases. A subject with controlled and asymptomatic CNS metastases may participate in this study. As such, the patient must have completed any prior treatment for CNS metastases \>= 28 days (including radiotherapy and/or surgery) prior to start of treatment in this study and should not be receiving chronic corticosteroid therapy for the CNS metastases. * Subjects with hemoptysis, central nervous system hemorrhage or gastrointestinal hemorrhage within the last 6 months prior to treatment are excluded due to pazopanib-associated risk of bleeding. * Subjects with severe hepatic impairment and active gastrointestinal bleeding. * Uncontrolled serious medical or psychiatric illness. * Subjects with a currently active second malignancy other than non-melanoma skin cancers, carcinoma in situ of the cervix, resected incidental prostate cancer, or other adequately treated carcinoma-in-situ are ineligible. Subjects are not considered to have a currently active malignancy if they have completed therapy and are free of disease for \>= 1 year). * Recent infection requiring systemic anti-infective treatment that was completed =\< 14 days prior to enrollment (with the exception of uncomplicated urinary tract infection or upper respiratory tract infection). * No clinically significant gastrointestinal abnormalities including malabsorption syndrome, major resection of the stomach or small bowel that could affect the absorption of study drug, active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis, or other gastrointestinal conditions with increased risk of perforation, history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment. * Uncontrolled diabetes mellitus as defined by hemoglobin A1C (HbA1c) \> 8% despite adequate therapy. * Subjects with unstable coronary artery disease, myocardial infarction, or an arterial thromboembolic event during preceding 6 months. * Subjects with history of interstitial lung disease and/or pneumonitis, or pulmonary hypertension. * Use of strong inhibitors and inducers of CYP3A4 within the 14 days prior to receiving the first dose of nab-sirolimus. Additionally, use of any known CYP3A4 substrates with narrow therapeutic window (such as fentanyl, alfentanil, astemizole, cisapride, dihydroergotamine, pimozide, quinidine, terfenadine) within the 14 days prior to receiving the first dose of nab-sirolimus. * Active hepatitis B or hepatitis C infection. * Systemic immunosuppression, including human immunodeficiency virus (HIV) positive status with or without acquired immunodeficiency syndrome (AIDS). * Subjects with history of intestinal perforations, fistula, hemorrhages and/or hemoptysis =\< 6 months prior to first study treatment. * Subjects with hypercholesterolemia receiving ongoing treatment with simvastatin. * Subjects who have had major surgery within 28 days of planned initiation of protocol therapy, or patients who have/have had wound dehiscence, or other open wounds (including diabetic or infectious wounds) with active wound complications. * Subjects with prior history of severe hypersensitivity (grade 3 or higher) to any known drug excipients, including anaphylaxis to human serum albumin. * Subjects with uncontrolled hypertension, defined as an average systolic blood pressure (SBP) \>= 140 mmHg or an average diastolic blood pressure (DBP) \>= 90 mmHg despite best supportive care measures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Maximum-tolerated Dose (MTD) of Nab-rapamycin in Combination With Pazopanib (Phase I) - Nab-Rapamycin Dose | First 2 cycles (3-week cycles, 21 days each) | Will be estimated using dose-limiting toxicities (DLTs). Will use a Simon's minimax design. |
| The Maximum-tolerated Dose (MTD) of Nab-rapamycin in Combination With Pazopanib (Phase I) - Pazopanib Dose | First 2 cycles (3-week cycles, 21 days each) | Will be estimated using dose-limiting toxicities (DLTs). Will use a Simon's minimax design. |
| Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | First 2 cycles (3-week cycles, 21 days each) | A DLT is defined as any Grade 3 or greater adverse event (AE), at least possibly related to either or both nab-sirolimus and pazopanib. Only toxicities with a clearly identified and documented alternative explanation may be deemed non-DLT. Dose-limiting toxicities include any death not clearly due to underlying disease or extraneous causes, or persistent intolerable nonhematologic AE of any grade that requires dose reduction or permanent discontinuation of the study drug, in the opinion of the investigator. |
| Dose Limiting Toxicities | First 2 cycles (3 week cycles, 21 days each) | A Dose-limiting toxicity is defined as any Grade 3 or greater adverse event (AE), at least possibly related to either or both nab-Sirolimus or pazopanib. Only toxicities with clearly identified and documented alternative explanation may be deemed non-DLT. Dose-limiting toxicities include any death not clearly due to underlying disease or extraneous causes, or persistent intolerable nonhematologic Ae of any grade that requires dose reduction or permanent discontinuation of the study drug, in the opinion of the investigator. |
| Progression-free Survival (PFS) Rate | At 3 months | Will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 where progression is defined as a 20% increase in the sum of the longest diameter of target lesions where the sum must also demonstrate an absolute increase of at least 5 mm, or the appearance of new lesions. Will be assessed via descriptive statistics. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (CR + PR) | Up to 2 years | Will be based on RECIST v1.1. Will be evaluated by CT imaging. |
| Incidence of Adverse Events Profile | Up to 30 days after last dose (an average of 41 weeks) | Treatment-related adverse events (AEs) experienced by participants evaluated by Common Terminology Criteria for Adverse Events (CTCAE) 5.0 and determined to be possibly related, probably related, or definitely related to either nab-sirolimus therapy, pazopanib therapy, or both. |
| Duration of Response | Up to 2 years | Will be evaluated by CT imaging. |
| Disease Control Rate (Complete Response [CR] + Partial Response [PR] + Stable Disease [SD]) | at 24 weeks | Will be based on RECIST v1.1evaluated by computed tomography (CT) imaging. Per RECIST V1.1, Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>= 30% decrease in the sum of diameters of target lesions; Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD). |
| Median PFS | At 6 months | Will be assessed using RECIST v1.1. Will be assessed via descriptive statistics. |
| Progression-Free Survival Rate | At 6 months | Will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. Will be assessed via descriptive statistics. |
| Median Overall Survival (OS) | At 12 months | Will be summarized using descriptive statistics. |
| Overall Survival | 12 months | Will be assessed using descriptive statistics. |
Countries
United States
Participant flow
Pre-assignment details
No participants were enrolled in Phase II of the study.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1, Dose Level 0 Participants received 60 mg/m\^2 of ABI-009 given intravenously on Day 1 and Day 8 of a 21 day cycle, plus daily oral 800 mg of pazopanib | 2 |
| Cohort 4, Dose Level -1 Participants received 45 mg/m\^2 of ABI-009 given intravenously on Day 1 and Day 8 of a 21 day cycle, plus daily oral 800 mg of pazopanib | 2 |
| Cohort 5, Dose Level -2 Participants received 30 mg/m\^2 of ABI-009 given intravenously on Day 1 and Day 8 of a 21 day cycle, plus daily oral 800 mg of pazopanib | 2 |
| Cohort 6, Dose Level 0B Participants received 60 mg/m\^2 of ABI-009 given intravenously on Day 1 and Day 8 of a 21 day cycle, plus daily oral 400 mg of pazopanib | 2 |
| Cohort 9, Dose Level -1B Participants received 45 mg/m\^2 of ABI-009 given intravenously on Day 1 and Day 8 of a 21 day cycle, plus daily oral 400 mg of pazopanib | 2 |
| Cohort 10, Dose Level -2B Participants received 30 mg/m\^2 of ABI-009 given intravenously on Day 1 and Day 8 of a 21 day cycle, plus daily oral 400 mg of pazopanib | 3 |
| Cohort 11, Dose Level 0C Participants received 30 mg/m\^2 of ABI-009 given intravenously on Day 1 of a 21 day cycle, plus daily oral 400 mg of pazopanib | 3 |
| Cohort 12, Dose Level 1C Participants received 45 mg/m\^2 of ABI-009 given intravenously on Day 1 of a 21 day cycle, plus daily oral 400 mg of pazopanib | 3 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 2 | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Cohort 4, Dose Level -1 | Cohort 5, Dose Level -2 | Cohort 6, Dose Level 0B | Cohort 9, Dose Level -1B | Cohort 1, Dose Level 0 | Cohort 10, Dose Level -2B | Cohort 11, Dose Level 0C | Cohort 12, Dose Level 1C | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized 18-29 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized 30-39 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized 40-49 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Age, Customized 50-59 | 2 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 2 Participants | 2 Participants | 9 Participants |
| Age, Customized 60-69 | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 5 Participants |
| Age, Customized 70 and over | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 2 Participants | 2 Participants | 2 Participants | 1 Participants | 3 Participants | 3 Participants | 3 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 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 | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 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 | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 2 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 2 Participants | 3 Participants | 3 Participants | 15 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 2 Participants | 2 Participants | 2 Participants | 11 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 8 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 | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 2 | 0 / 2 | 0 / 2 | 0 / 2 | 1 / 3 | 0 / 3 | 0 / 3 |
| other Total, other adverse events | 2 / 2 | 2 / 2 | 2 / 2 | 2 / 2 | 2 / 2 | 3 / 3 | 3 / 3 | 3 / 3 |
| serious Total, serious adverse events | 2 / 2 | 0 / 2 | 0 / 2 | 1 / 2 | 0 / 2 | 1 / 3 | 0 / 3 | 1 / 3 |
Outcome results
Primary
Dose Limiting Toxicities
A Dose-limiting toxicity is defined as any Grade 3 or greater adverse event (AE), at least possibly related to either or both nab-Sirolimus or pazopanib. Only toxicities with clearly identified and documented alternative explanation may be deemed non-DLT. Dose-limiting toxicities include any death not clearly due to underlying disease or extraneous causes, or persistent intolerable nonhematologic Ae of any grade that requires dose reduction or permanent discontinuation of the study drug, in the opinion of the investigator.
Time frame: First 2 cycles (3 week cycles, 21 days each)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Participants | Dose Limiting Toxicities | WBC decreased, Neutropenia | 1 participants |
| All Participants | Dose Limiting Toxicities | Neutropenia | 0 participants |
| All Participants | Dose Limiting Toxicities | Thrombocytopenia, Neutropenia | 0 participants |
| All Participants | Dose Limiting Toxicities | Lipase elevated | 0 participants |
| All Participants | Dose Limiting Toxicities | Proteinuria | 0 participants |
| All Participants | Dose Limiting Toxicities | Thrombocytopenia | 1 participants |
| All Participants | Dose Limiting Toxicities | No DLT experienced | 0 participants |
| All Participants | Dose Limiting Toxicities | Thrombocytopenia, Oral mucositis | 0 participants |
| Cohort 4, Dose Level -1 | Dose Limiting Toxicities | Neutropenia | 1 participants |
| Cohort 4, Dose Level -1 | Dose Limiting Toxicities | Lipase elevated | 1 participants |
| Cohort 4, Dose Level -1 | Dose Limiting Toxicities | WBC decreased, Neutropenia | 0 participants |
| Cohort 4, Dose Level -1 | Dose Limiting Toxicities | Thrombocytopenia | 0 participants |
| Cohort 4, Dose Level -1 | Dose Limiting Toxicities | Proteinuria | 0 participants |
| Cohort 4, Dose Level -1 | Dose Limiting Toxicities | Thrombocytopenia, Neutropenia | 0 participants |
| Cohort 4, Dose Level -1 | Dose Limiting Toxicities | Thrombocytopenia, Oral mucositis | 0 participants |
| Cohort 4, Dose Level -1 | Dose Limiting Toxicities | No DLT experienced | 0 participants |
| Cohort 5, Dose Level -2 | Dose Limiting Toxicities | WBC decreased, Neutropenia | 0 participants |
| Cohort 5, Dose Level -2 | Dose Limiting Toxicities | No DLT experienced | 0 participants |
| Cohort 5, Dose Level -2 | Dose Limiting Toxicities | Lipase elevated | 0 participants |
| Cohort 5, Dose Level -2 | Dose Limiting Toxicities | Proteinuria | 1 participants |
| Cohort 5, Dose Level -2 | Dose Limiting Toxicities | Neutropenia | 0 participants |
| Cohort 5, Dose Level -2 | Dose Limiting Toxicities | Thrombocytopenia | 1 participants |
| Cohort 5, Dose Level -2 | Dose Limiting Toxicities | Thrombocytopenia, Oral mucositis | 0 participants |
| Cohort 5, Dose Level -2 | Dose Limiting Toxicities | Thrombocytopenia, Neutropenia | 0 participants |
| Cohort 6, Dose Level 0B | Dose Limiting Toxicities | Thrombocytopenia, Neutropenia | 0 participants |
| Cohort 6, Dose Level 0B | Dose Limiting Toxicities | Lipase elevated | 0 participants |
| Cohort 6, Dose Level 0B | Dose Limiting Toxicities | Proteinuria | 0 participants |
| Cohort 6, Dose Level 0B | Dose Limiting Toxicities | WBC decreased, Neutropenia | 0 participants |
| Cohort 6, Dose Level 0B | Dose Limiting Toxicities | Thrombocytopenia, Oral mucositis | 0 participants |
| Cohort 6, Dose Level 0B | Dose Limiting Toxicities | Neutropenia | 0 participants |
| Cohort 6, Dose Level 0B | Dose Limiting Toxicities | Thrombocytopenia | 2 participants |
| Cohort 6, Dose Level 0B | Dose Limiting Toxicities | No DLT experienced | 0 participants |
| Cohort 9, Dose Level -1B | Dose Limiting Toxicities | Proteinuria | 0 participants |
| Cohort 9, Dose Level -1B | Dose Limiting Toxicities | Neutropenia | 0 participants |
| Cohort 9, Dose Level -1B | Dose Limiting Toxicities | Thrombocytopenia, Oral mucositis | 1 participants |
| Cohort 9, Dose Level -1B | Dose Limiting Toxicities | Thrombocytopenia, Neutropenia | 0 participants |
| Cohort 9, Dose Level -1B | Dose Limiting Toxicities | Thrombocytopenia | 1 participants |
| Cohort 9, Dose Level -1B | Dose Limiting Toxicities | WBC decreased, Neutropenia | 0 participants |
| Cohort 9, Dose Level -1B | Dose Limiting Toxicities | Lipase elevated | 0 participants |
| Cohort 9, Dose Level -1B | Dose Limiting Toxicities | No DLT experienced | 0 participants |
| Cohort 10, Dose Level -2B | Dose Limiting Toxicities | Thrombocytopenia | 1 participants |
| Cohort 10, Dose Level -2B | Dose Limiting Toxicities | No DLT experienced | 1 participants |
| Cohort 10, Dose Level -2B | Dose Limiting Toxicities | WBC decreased, Neutropenia | 0 participants |
| Cohort 10, Dose Level -2B | Dose Limiting Toxicities | Thrombocytopenia, Neutropenia | 1 participants |
| Cohort 10, Dose Level -2B | Dose Limiting Toxicities | Neutropenia | 0 participants |
| Cohort 10, Dose Level -2B | Dose Limiting Toxicities | Thrombocytopenia, Oral mucositis | 0 participants |
| Cohort 10, Dose Level -2B | Dose Limiting Toxicities | Lipase elevated | 0 participants |
| Cohort 10, Dose Level -2B | Dose Limiting Toxicities | Proteinuria | 0 participants |
| Cohort 11, Dose Level 0C | Dose Limiting Toxicities | Thrombocytopenia, Oral mucositis | 0 participants |
| Cohort 11, Dose Level 0C | Dose Limiting Toxicities | Thrombocytopenia | 0 participants |
| Cohort 11, Dose Level 0C | Dose Limiting Toxicities | Proteinuria | 0 participants |
| Cohort 11, Dose Level 0C | Dose Limiting Toxicities | WBC decreased, Neutropenia | 0 participants |
| Cohort 11, Dose Level 0C | Dose Limiting Toxicities | No DLT experienced | 3 participants |
| Cohort 11, Dose Level 0C | Dose Limiting Toxicities | Lipase elevated | 0 participants |
| Cohort 11, Dose Level 0C | Dose Limiting Toxicities | Neutropenia | 0 participants |
| Cohort 11, Dose Level 0C | Dose Limiting Toxicities | Thrombocytopenia, Neutropenia | 0 participants |
| Cohort 12, Dose Level 1C | Dose Limiting Toxicities | Proteinuria | 0 participants |
| Cohort 12, Dose Level 1C | Dose Limiting Toxicities | WBC decreased, Neutropenia | 0 participants |
| Cohort 12, Dose Level 1C | Dose Limiting Toxicities | No DLT experienced | 1 participants |
| Cohort 12, Dose Level 1C | Dose Limiting Toxicities | Thrombocytopenia | 2 participants |
| Cohort 12, Dose Level 1C | Dose Limiting Toxicities | Neutropenia | 0 participants |
| Cohort 12, Dose Level 1C | Dose Limiting Toxicities | Lipase elevated | 0 participants |
| Cohort 12, Dose Level 1C | Dose Limiting Toxicities | Thrombocytopenia, Neutropenia | 0 participants |
| Cohort 12, Dose Level 1C | Dose Limiting Toxicities | Thrombocytopenia, Oral mucositis | 0 participants |
Primary
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
A DLT is defined as any Grade 3 or greater adverse event (AE), at least possibly related to either or both nab-sirolimus and pazopanib. Only toxicities with a clearly identified and documented alternative explanation may be deemed non-DLT. Dose-limiting toxicities include any death not clearly due to underlying disease or extraneous causes, or persistent intolerable nonhematologic AE of any grade that requires dose reduction or permanent discontinuation of the study drug, in the opinion of the investigator.
Time frame: First 2 cycles (3-week cycles, 21 days each)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| All Participants | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 2 Participants |
| Cohort 4, Dose Level -1 | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 2 Participants |
| Cohort 5, Dose Level -2 | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 2 Participants |
| Cohort 6, Dose Level 0B | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 2 Participants |
| Cohort 9, Dose Level -1B | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 2 Participants |
| Cohort 10, Dose Level -2B | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 2 Participants |
| Cohort 11, Dose Level 0C | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 0 Participants |
| Cohort 12, Dose Level 1C | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 2 Participants |
Primary
Progression-free Survival (PFS) Rate
Will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 where progression is defined as a 20% increase in the sum of the longest diameter of target lesions where the sum must also demonstrate an absolute increase of at least 5 mm, or the appearance of new lesions. Will be assessed via descriptive statistics.
Time frame: At 3 months
Population: Three Phase I patients were treated at the recommended Phase II dose of 30 mg/m\^2 nab-sirolimus intravenously on Day 1 of a 21-day cycle, with 400 mg of oral daily pazopanib. These three patients were not enrolled in Phase II.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | Progression-free Survival (PFS) Rate | 0.33 proportion of participants |
Primary
The Maximum-tolerated Dose (MTD) of Nab-rapamycin in Combination With Pazopanib (Phase I) - Nab-Rapamycin Dose
Will be estimated using dose-limiting toxicities (DLTs). Will use a Simon's minimax design.
Time frame: First 2 cycles (3-week cycles, 21 days each)
Population: MTD was determined to be ABI-009 on DAY 1 of a 21 day cycle ONLY in combination with daily oral pazopanib.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | The Maximum-tolerated Dose (MTD) of Nab-rapamycin in Combination With Pazopanib (Phase I) - Nab-Rapamycin Dose | 30 mg/m^2 |
Primary
The Maximum-tolerated Dose (MTD) of Nab-rapamycin in Combination With Pazopanib (Phase I) - Pazopanib Dose
Will be estimated using dose-limiting toxicities (DLTs). Will use a Simon's minimax design.
Time frame: First 2 cycles (3-week cycles, 21 days each)
Population: MTD was determined to be ABI-009 on DAY 1 of a 21 day cycle ONLY in combination with daily oral pazopanib.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | The Maximum-tolerated Dose (MTD) of Nab-rapamycin in Combination With Pazopanib (Phase I) - Pazopanib Dose | 400 mg |
Secondary
Disease Control Rate (Complete Response [CR] + Partial Response [PR] + Stable Disease [SD])
Will be based on RECIST v1.1evaluated by computed tomography (CT) imaging. Per RECIST V1.1, Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>= 30% decrease in the sum of diameters of target lesions; Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD).
Time frame: at 24 weeks
Population: Three Phase I patients were treated at the recommended Phase II dose of 30 mg/m\^2 nab-sirolimus intravenously on Day 1 of a 21-day cycle with 400 mg of oral daily pazopanib. These three patients were not enrolled in Phase II.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | Disease Control Rate (Complete Response [CR] + Partial Response [PR] + Stable Disease [SD]) | 0.33 proportion of participants |
Secondary
Duration of Response
Will be evaluated by CT imaging.
Time frame: Up to 2 years
Population: Three Phase I patients were treated at the recommended Phase II dose of 30 mg/m\^2 nab-sirolimus intravenously on Day 1 of a 21-day cycle with 400 mg of oral daily pazopanib. These three patients were not enrolled in Phase II.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| All Participants | Duration of Response | NA months |
Secondary
Incidence of Adverse Events Profile
Treatment-related adverse events (AEs) experienced by participants evaluated by Common Terminology Criteria for Adverse Events (CTCAE) 5.0 and determined to be possibly related, probably related, or definitely related to either nab-sirolimus therapy, pazopanib therapy, or both.
Time frame: Up to 30 days after last dose (an average of 41 weeks)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Participants | Incidence of Adverse Events Profile | Grade 5 | 0 adverse events experienced |
| All Participants | Incidence of Adverse Events Profile | Grade 3 | 10 adverse events experienced |
| All Participants | Incidence of Adverse Events Profile | Grade 2 | 30 adverse events experienced |
| All Participants | Incidence of Adverse Events Profile | Grade 4 | 0 adverse events experienced |
| All Participants | Incidence of Adverse Events Profile | Grade 1 | 34 adverse events experienced |
| Cohort 4, Dose Level -1 | Incidence of Adverse Events Profile | Grade 5 | 0 adverse events experienced |
| Cohort 4, Dose Level -1 | Incidence of Adverse Events Profile | Grade 1 | 25 adverse events experienced |
| Cohort 4, Dose Level -1 | Incidence of Adverse Events Profile | Grade 4 | 0 adverse events experienced |
| Cohort 4, Dose Level -1 | Incidence of Adverse Events Profile | Grade 2 | 22 adverse events experienced |
| Cohort 4, Dose Level -1 | Incidence of Adverse Events Profile | Grade 3 | 1 adverse events experienced |
| Cohort 5, Dose Level -2 | Incidence of Adverse Events Profile | Grade 2 | 6 adverse events experienced |
| Cohort 5, Dose Level -2 | Incidence of Adverse Events Profile | Grade 5 | 0 adverse events experienced |
| Cohort 5, Dose Level -2 | Incidence of Adverse Events Profile | Grade 3 | 3 adverse events experienced |
| Cohort 5, Dose Level -2 | Incidence of Adverse Events Profile | Grade 1 | 11 adverse events experienced |
| Cohort 5, Dose Level -2 | Incidence of Adverse Events Profile | Grade 4 | 0 adverse events experienced |
| Cohort 6, Dose Level 0B | Incidence of Adverse Events Profile | Grade 1 | 16 adverse events experienced |
| Cohort 6, Dose Level 0B | Incidence of Adverse Events Profile | Grade 2 | 16 adverse events experienced |
| Cohort 6, Dose Level 0B | Incidence of Adverse Events Profile | Grade 3 | 8 adverse events experienced |
| Cohort 6, Dose Level 0B | Incidence of Adverse Events Profile | Grade 4 | 4 adverse events experienced |
| Cohort 6, Dose Level 0B | Incidence of Adverse Events Profile | Grade 5 | 0 adverse events experienced |
| Cohort 9, Dose Level -1B | Incidence of Adverse Events Profile | Grade 2 | 22 adverse events experienced |
| Cohort 9, Dose Level -1B | Incidence of Adverse Events Profile | Grade 5 | 0 adverse events experienced |
| Cohort 9, Dose Level -1B | Incidence of Adverse Events Profile | Grade 1 | 21 adverse events experienced |
| Cohort 9, Dose Level -1B | Incidence of Adverse Events Profile | Grade 3 | 5 adverse events experienced |
| Cohort 9, Dose Level -1B | Incidence of Adverse Events Profile | Grade 4 | 0 adverse events experienced |
| Cohort 10, Dose Level -2B | Incidence of Adverse Events Profile | Grade 2 | 34 adverse events experienced |
| Cohort 10, Dose Level -2B | Incidence of Adverse Events Profile | Grade 4 | 2 adverse events experienced |
| Cohort 10, Dose Level -2B | Incidence of Adverse Events Profile | Grade 3 | 10 adverse events experienced |
| Cohort 10, Dose Level -2B | Incidence of Adverse Events Profile | Grade 5 | 0 adverse events experienced |
| Cohort 10, Dose Level -2B | Incidence of Adverse Events Profile | Grade 1 | 29 adverse events experienced |
| Cohort 11, Dose Level 0C | Incidence of Adverse Events Profile | Grade 3 | 0 adverse events experienced |
| Cohort 11, Dose Level 0C | Incidence of Adverse Events Profile | Grade 2 | 8 adverse events experienced |
| Cohort 11, Dose Level 0C | Incidence of Adverse Events Profile | Grade 4 | 0 adverse events experienced |
| Cohort 11, Dose Level 0C | Incidence of Adverse Events Profile | Grade 5 | 0 adverse events experienced |
| Cohort 11, Dose Level 0C | Incidence of Adverse Events Profile | Grade 1 | 15 adverse events experienced |
| Cohort 12, Dose Level 1C | Incidence of Adverse Events Profile | Grade 2 | 15 adverse events experienced |
| Cohort 12, Dose Level 1C | Incidence of Adverse Events Profile | Grade 5 | 0 adverse events experienced |
| Cohort 12, Dose Level 1C | Incidence of Adverse Events Profile | Grade 3 | 5 adverse events experienced |
| Cohort 12, Dose Level 1C | Incidence of Adverse Events Profile | Grade 1 | 22 adverse events experienced |
| Cohort 12, Dose Level 1C | Incidence of Adverse Events Profile | Grade 4 | 0 adverse events experienced |
Secondary
Median Overall Survival (OS)
Will be summarized using descriptive statistics.
Time frame: At 12 months
Population: Three Phase I patients were treated at the recommended Phase II dose of 30 mg/m\^2 nab-sirolimus intravenously on Day 1 of a 21-day cycle with 400 mg of oral daily pazopanib. These three patients were not enrolled in Phase II.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| All Participants | Median Overall Survival (OS) | 11.1 months |
Secondary
Median PFS
Will be assessed using RECIST v1.1. Will be assessed via descriptive statistics.
Time frame: At 6 months
Population: Three Phase I patients were treated at the recommended Phase II dose of 30 mg/m\^2 nab-sirolimus intravenously on Day 1 of a 21-day cycle with 400 mg of oral daily pazopanib. These three patients were not enrolled in Phase II.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| All Participants | Median PFS | 1.2 months |
Secondary
Objective Response Rate (CR + PR)
Will be based on RECIST v1.1. Will be evaluated by CT imaging.
Time frame: Up to 2 years
Population: Three Phase I patients were treated at the recommended Phase II dose of 30 mg/m\^2 nab-sirolimus intravenously on Day 1 of a 21-day cycle with 400 mg of oral daily pazopanib. These three patients were not enrolled in Phase II.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | Objective Response Rate (CR + PR) | 0.00 proportion of participants |
Secondary
Overall Survival
Will be assessed using descriptive statistics.
Time frame: 12 months
Population: Three Phase I patients were treated at the recommended Phase II dose of 30 mg/m\^2 nab-sirolimus intravenously on Day 1 of a 21-day cycle with 400 mg of oral daily pazopanib. These three patients were not enrolled in Phase II.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | Overall Survival | .33 proportion of participants |
Secondary
Progression-Free Survival Rate
Will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. Will be assessed via descriptive statistics.
Time frame: At 6 months
Population: Three Phase I patients were treated at the recommended Phase II dose of 30 mg/m\^2 nab-sirolimus intravenously on Day 1 of a 21-day cycle with 400 mg of oral daily pazopanib. These three patients were not enrolled in Phase II.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | Progression-Free Survival Rate | 0.33 proportion of participants |