Metastatic Pancreatic Cancer
Conditions
Keywords
pancreatic cancer, Abraxane, first line
Brief summary
This will be a Phase 1b/2a multicenter 2-stage study. Phase 1 will be conducted as a dose-finding, open-label study of oral RX-3117 administered in combination with Abraxane® to subjects with metastatic pancreatic cancer. After completion of the Phase 1 portion, a Phase 2a study will be conducted using a 2 stage, open-label design, of RX 3117 and Abraxane® in combination to treat subjects with metastatic pancreatic cancer as first line therapy.
Detailed description
This will be a Phase 1b/2a multicenter 2-stage study. Phase 1 will be conducted as a dose-finding, open-label study of oral RX-3117 administered in combination with Abraxane® to subjects with metastatic pancreatic cancer. The recommended phase 2 dose (RP2D) and schedule of RX-3117, in combination with Abraxane®, will be determined based on the safety profile, dose modification, and pharmacokinetics (PK). Phase 1 will be conducted using a combination of the single agent maximum tolerated dose (MTD) for RX-3117 and the Abraxane dose as per the package insert for patients with pancreatic cancer in combination with gemcitabine. After completion of the Phase 1 portion, a Phase 2a study will be conducted using a 2 stage, open-label design, of RX 3117 and Abraxane® in combination to treat subjects with metastatic pancreatic cancer as first line therapy. Approximately 10 subjects will participate in the Stage 1 at the dose identified in Phase 1 (RP2D). Subjects will be treated for up to 8 cycles of combined therapy. An interim analysis will be conducted after 10 evaluable subjects have been treated at the RP2D, have completed a minimum of 4 cycles of therapy, or have discontinued therapy due to progressive disease before completing 4 cycles. If an adequate number of Responders are observed out of the initial 10 evaluable subjects, then 40 additional subjects will be enrolled to participate in Stage 2. Subjects will be treated for up to 8 cycles of combined therapy.
Interventions
DRUGRX-3117
RX-3117 will be administered orally in combination with Abraxane.
Sponsors
Processa Pharmaceuticals
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
Disease Related 1. Subject has confirmed histologic or cytologic evidence of metastatic pancreatic cancer and has no prior treatment for metastatic pancreatic cancer. 2. Subject has measurable disease using Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1. 3. Subject has a life expectancy of at least 3 months. 4. Subject has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. Demographic 5. Males or females ≥ 18 years of age 6. Subject must be able to swallow capsules 7. Subject must have adequate venous access for intravenous (IV) infusion Laboratory 8. Subject has hemoglobin ≥ 9.0 g/dL at Screening 9. Subject has absolute neutrophil count (ANC) ≥ 1.5 x 109/L at Screening 10. Subject has platelet count ≥ 100 x 109/L at Screening 11. Subject has serum creatinine ≤ 1.5 times the upper limit of normal (ULN) at Screening. Subjects with serum creatinine levels \> 1.5 times the ULN must have a 24-hour urine creatinine clearance ≥ 60 mL/min 12. Subject has serum bilirubin ≤ 1.5 times the ULN (except in subjects with Gilbert's Syndrome who must have serum bilirubin \< 3.0 x ULN) 13. Subject has aspartate aminotransferase (AST; SGOT) and alanine aminotransferase (ALT; SGPT) ≤ 2.5 times the ULN (OR, AST and ALT ≤ 5 times the ULN in the presence of known liver metastases) 14. Subject has alkaline phosphatase ≤ 2.5 times the ULN (OR ≤ 5 times the ULN in the presence of known liver or bone metastases) 15. Subject has normal coagulation parameters (prothrombin time \[PT\] and/or international normalized ratio \[INR\], and partial thromboplastin time \[PTT\] within normal limits \[\<1.2 x ULN\]) 16. Subject has potassium concentration within normal range, or correctable with supplements. 17. Oxygen saturation by pulse oximetry ≥ 92% at rest. 18. For women of childbearing potential: Negative serum pregnancy test during screening and negative serum or urine pregnancy test at start of study therapy (Cycle1 Day 1). Reproductive 19. For female subjects of childbearing potential, willingness to abstain from heterosexual intercourse or use a protocol-recommended method of contraception from the screening visit throughout the study treatment period and for 30 days following the last dose of study drug. 20. Female subjects of non-childbearing potential defined as having amenorrhea for at least 24 consecutive months, a documented hysterectomy, or a documented bilateral oophorectomy) 21. For fertile male subjects having intercourse with females of childbearing potential, willingness to abstain from heterosexual intercourse or use a protocol-recommended method of contraception from the start of study therapy throughout the study treatment period and for 30 days following the last dose of study drug and to refrain from sperm donation from the start of study treatment throughout the study treatment period and for 30 days following the last dose of study drug. Ethical 22. In the judgment of the investigator, participation in the protocol offers an acceptable benefit-to-risk ratio when considering current disease status, medical condition, and the potential benefits and risks of alternative treatments for the subject's cancer. 23. Before any study-specific procedure, the appropriate written informed consent must be obtained
Exclusion criteria
Disease Related 1. Subject has primary brain tumors or clinical evidence of active brain metastasis 2. Subject has undergone major surgery within 4 weeks of the start of study treatment. Laparoscopy and central venous catheter placement are not considered major surgery Medications 3. Subject has a history of systemic corticosteroid use within 7 days before Day 1 of Cycle 1 General 4. Subject has an active infection requiring parenteral or oral antibiotics within 2 weeks before planned start of study therapy 5. Subject has uncontrolled diabetes as assessed by the investigator 6. Subject has a second malignancy other than curatively resected basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ carcinoma of the cervix, or other cancers treated with curative intent and no known active disease within 3 years before planned start of study therapy 7. Subject has an active infection of hepatitis B, hepatitis C or human immunodeficiency virus 8. Female subjects who are pregnant, planning a pregnancy or breast feeding during the study 9. Subject has a high cardiovascular risk, including, but not limited to, subjects with congestive heart failure (New York Heart Association \[NYHA\] Class III or IV), cardiac arrhythmia, unstable angina, coronary stenting or acute coronary syndromes within 6 months before planned start of study therapy or r myocardial infarction within one year before planned start of study therapy 10. Criterion removed 11. Subject has a history of prior allogeneic bone marrow progenitor cell or solid organ transplantation. 12. Subject has known acute or chronic pancreatitis. 13. Subject has persistent diarrhea, malabsorption, or known sub-acute bowel obstruction ≥ NCI CTCAE Grade 2, despite medical management. 14. Subject has any disorder that may interfere with drug absorption, distribution, metabolism, or excretion (including gastrointestinal surgery and bariatric surgery) 15. All acute toxic effects of any prior antitumor therapy resolved to Grade ≤ 1 before the start of study therapy (with the exception of alopecia \[Grade 1 or 2 permitted\], or neurotoxicity \[Grade 1 or 2 permitted\], or anemia \[Grade 2 permitted\]) 16. Subject has any other medical, psychiatric, or social condition, which in the opinion of the investigator, would preclude participation in the study, pose an undue medical hazard, interfere with the conduct of the study, or interfere with interpretation of the study results 17. Subject has a history of interstitial lung disease, slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies. Any lung disease that may interfere with the detection or management of suspected drug-related pulmonary toxicity. 18. Subject is currently enrolled in any other clinical protocol or investigational trial that involves administration of experimental therapy and/or therapeutic devices, or investigational drug. 19. Subject has a history of hypersensitivity to RX-3117, gemcitabine, azacytidine cytosine arabinoside, paclitaxel, nab-paclitaxel, or their excipients. 20. Subject is unwilling or unable to comply with study requirements or planned unavailability for follow-up assessments.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Progression Free Survival (PFS) and/or Objective Clinical Response (Phase 2) | 9 months | Participants must have progression Free Survival (PFS) \> 4 months or objective clinical response (complete or partial response). |
| Number of Dose-limiting Toxicities (DLTs) (Phase 1) | 4 weeks | — |
| Number of Participants With Electrocardiogram (ECG) Abnormalities (Phase 1 and 2) | 1 month | Number of participants with clinically significant ECG abnormalities (Phase 1 and 2) |
| Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 (Phase 1 and 2) | 9 months | Number of participants who experienced a treatment-related adverse event |
| Number of Participants With Clinical Laboratory Abnormalities (Phase 1 and 2) | 9 months | Participants with adverse events coded using the MedDRA Dictionary (Version 20.0) to Investigations. Due to the underlying disease, not all abnormal labs are reported. |
| Number of Participants With Vital Sign Abnormalities (Phase 1 and 2) | 9 months | Number of participants with clinically significant vital sign abnormalities (Phase 1 and 2) including heart rate, respiration rate, and blood pressure |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response [DOR] (Phase 1 and Phase 2) | Up to 32 weeks | Duration of response is defined as the time from documentation of response to disease progression. |
| Progression-free Survival [PFS] (Phase 1) | Every 8 weeks until progression or discontinuation, whichever came first, assessed up to 32 weeks | Progression Free Survival defined as the percentage of subjects who are alive in the study and not in progression. |
| Time to Progression (Phase 2) | Every 8 weeks until progression or discontinuation, whichever came first, assessed up to 32 weeks | Time to Progression defined as the time from first treatment administration to first documentation of RECIST-defined objective tumor progression. |
| Area Under the Plasma Concentration Versus Time Curve (AUC) of RX-3117 and Abraxane® (Phase 1 and Phase 2) - Day 15 | Day 15 (pre-infusion, post-infusion, pre-dose RX-3117, and 0.5, 1, 2, 4, and 6 hours after administration) | — |
| Area Under the Plasma Concentration Versus Time Curve (AUC) of Abraxane® (Phase 1 and Phase 2) - Day 1 | Cycle 1 Day 1 (pre-infusion, post-infusion, pre-dose RX-3117, and 0.5, 1, 2, 4, 6, and 24 hours after administration) | — |
| Time to Maximum Observed Concentration [Tmax] of RX-3117 (Phase 1 and Phase 2) - Day 15 | Day 15 (pre-infusion, post-infusion, pre-dose RX-3117, and 0.5, 1, 2, 4, and 6 hours after administration) | — |
| Time to Maximum Observed Concentration [Tmax] of Abraxane® (Phase 1 and Phase 2) - Day 1 | Cycle 1 Days 1 (pre-infusion, post-infusion, pre-dose RX-3117, and 0.5, 1, 2, 4, 6, and 24 hours after administration) | — |
| Time to Maximum Observed Concentration [Tmax] of Abraxane® (Phase 1 and Phase 2) - Day 15 | Day 15 (pre-infusion, post-infusion, pre-dose RX-3117, and 0.5, 1, 2, 4, and 6 hours after administration) | — |
| Maximum Observed Concentration [Cmax] of RX-3117 (Phase 1 and Phase 2) - Day 15 | Day 15 (pre-infusion, post-infusion, pre-dose RX-3117, and 0.5, 1, 2, 4, and 6 hours after administration) | — |
| Maximum Observed Concentration [Cmax] of Abraxane (Phase 1 and Phase 2) - Day 1 | Cycle 1 Days 1 (pre-infusion, post-infusion, pre-dose RX-3117, and 0.5, 1, 2, 4, 6, and 24 hours after administration) | — |
| Maximum Observed Concentration [Cmax] of Abraxane (Phase 1 and Phase 2) - Day 15 | Day 15 (pre-infusion, post-infusion, pre-dose RX-3117, and 0.5, 1, 2, 4, and 6 hours after administration) | — |
| Area Under the Plasma Concentration Versus Time Curve (AUC) of Abraxane®(Phase 1 and Phase 2) - Day 15 | Day 15 (pre-infusion, post-infusion, pre-dose RX-3117, and 0.5, 1, 2, 4, and 6 hours after administration) | — |
| Area Under the Plasma Concentration Versus Time Curve (AUC) of RX-3117 (Phase 1 and Phase 2) - Day 1 | Cycle 1 Day 1 (pre-infusion, post-infusion, pre-dose RX-3117, and 0.5, 1, 2, 4, 6, and 24 hours after administration) | — |
| Time to Maximum Observed Concentration [Tmax] of RX-3117 (Phase 1 and Phase 2) - Day 1 | Cycle 1 Days 1 (pre-infusion, post-infusion, pre-dose RX-3117, and 0.5, 1, 2, 4, 6, and 24 hours after administration) | — |
| Maximum Observed Concentration [Cmax] of RX-3117 (Phase 1 and Phase 2) - Day 1 | Cycle 1 Days 1 (pre-infusion, post-infusion, pre-dose RX-3117, and 0.5, 1, 2, 4, 6, and 24 hours after administration) | — |
| Overall Response Rate [ORR] (Phase 1 and Phase 2) | Every 8 weeks until progression or discontinuation, whichever came first, assessed up to 32 weeks | Overall Response Rate will be based on the RECIST v1.1 and is defined as the percentage of subjects meeting criteria of Complete Response (CR) or Partial Response (PR). CR or PR must be confirmed at least 4 weeks after the date of the original CR or PR. |
| Time to Response [TTR] (Phase 1) | Up to 32 weeks | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploratory Measurement of Protein Biomarkers Related to RX-3117 or Pancreatic Cancer (Phase 1 and 2) | Baseline, and at 8, 6, 24, and 32 weeks | — |
| Quality of Life (QOL) (Phase 1 and 2) | 9 months | Weekly patient reported quality of life measures using validated QOL questionnaires |
| Tumor Burden Response (Phase 2) | Baseline, and at 8, 6, 24, and 32 weeks | Changes in tumor burden response via tumor marker measurement |
Countries
United States
Participant flow
Pre-assignment details
Phase 1: The arm was designed as a dose de-escalation. De-escalation was not required during Phase 1, therefore, the starting dose 700mg RX-3117 + 125 mg/m\^2 Abraxane was the only dose tested.
Participants by arm
| Arm | Count |
|---|---|
| RX-3117 + Abraxane Phase 1 RX-3117: oral, 700 mg/ day for 5 days on/ 2 days off for 3 weeks. 1 washout week/ cycle.
Abraxane: 125 mg/m\^2, infused once per week for 3 weeks. 1 washout week/ cycle.
RX-3117: RX-3117 will be administered orally in combination with Abraxane. | 8 |
| RX-3117 + Abraxane Phase 2 RX-3117: oral, 700 mg/ day for 5 days on/ 2 days off for 3 weeks. 1 washout week/ cycle.
Abraxane: 125 mg/m\^2, infused once per week for 3 weeks. 1 washout week/ cycle.
RX-3117: RX-3117 will be administered orally in combination with Abraxane. | 38 |
| Total | 46 |
Baseline characteristics
| Characteristic | RX-3117 + Abraxane Phase 1 | Total | RX-3117 + Abraxane Phase 2 |
|---|---|---|---|
| Age, Continuous | 66 years STANDARD_DEVIATION 70.5 | 66.3 years STANDARD_DEVIATION 67 | 66.3 years STANDARD_DEVIATION 66 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 6 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 39 Participants | 32 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 4 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 42 Participants | 34 Participants |
| Region of Enrollment United States | 8 participants | 46 participants | 38 participants |
| Sex: Female, Male Female | 5 Participants | 24 Participants | 19 Participants |
| Sex: Female, Male Male | 3 Participants | 22 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 2 / 38 |
| other Total, other adverse events | 8 / 8 | 38 / 38 |
| serious Total, serious adverse events | 3 / 8 | 18 / 38 |
Outcome results
Primary
Number of Dose-limiting Toxicities (DLTs) (Phase 1)
Time frame: 4 weeks
Population: Phase 1 participants receiving at least 10 doses in Cycle 1 and eligible for DLT evaluation.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RX-3117 + Abraxane Phase 1 | Number of Dose-limiting Toxicities (DLTs) (Phase 1) | 0 Participants |
Primary
Number of Participants With Clinical Laboratory Abnormalities (Phase 1 and 2)
Participants with adverse events coded using the MedDRA Dictionary (Version 20.0) to Investigations. Due to the underlying disease, not all abnormal labs are reported.
Time frame: 9 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RX-3117 + Abraxane Phase 1 | Number of Participants With Clinical Laboratory Abnormalities (Phase 1 and 2) | 4 Participants |
| RX-3117 + Abraxane Phase 2 | Number of Participants With Clinical Laboratory Abnormalities (Phase 1 and 2) | 18 Participants |
Primary
Number of Participants With Electrocardiogram (ECG) Abnormalities (Phase 1 and 2)
Number of participants with clinically significant ECG abnormalities (Phase 1 and 2)
Time frame: 1 month
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RX-3117 + Abraxane Phase 1 | Number of Participants With Electrocardiogram (ECG) Abnormalities (Phase 1 and 2) | 0 Participants |
| RX-3117 + Abraxane Phase 2 | Number of Participants With Electrocardiogram (ECG) Abnormalities (Phase 1 and 2) | 0 Participants |
Primary
Number of Participants With Progression Free Survival (PFS) and/or Objective Clinical Response (Phase 2)
Participants must have progression Free Survival (PFS) \> 4 months or objective clinical response (complete or partial response).
Time frame: 9 months
Population: Modified ITT population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RX-3117 + Abraxane Phase 1 | Number of Participants With Progression Free Survival (PFS) and/or Objective Clinical Response (Phase 2) | 17 Participants |
Primary
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 (Phase 1 and 2)
Number of participants who experienced a treatment-related adverse event
Time frame: 9 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RX-3117 + Abraxane Phase 1 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 (Phase 1 and 2) | 8 Participants |
| RX-3117 + Abraxane Phase 2 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 (Phase 1 and 2) | 38 Participants |
Primary
Number of Participants With Vital Sign Abnormalities (Phase 1 and 2)
Number of participants with clinically significant vital sign abnormalities (Phase 1 and 2) including heart rate, respiration rate, and blood pressure
Time frame: 9 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RX-3117 + Abraxane Phase 1 | Number of Participants With Vital Sign Abnormalities (Phase 1 and 2) | 0 Participants |
| RX-3117 + Abraxane Phase 2 | Number of Participants With Vital Sign Abnormalities (Phase 1 and 2) | 0 Participants |
Secondary
Area Under the Plasma Concentration Versus Time Curve (AUC) of Abraxane® (Phase 1 and Phase 2) - Day 1
Time frame: Cycle 1 Day 1 (pre-infusion, post-infusion, pre-dose RX-3117, and 0.5, 1, 2, 4, 6, and 24 hours after administration)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RX-3117 + Abraxane Phase 1 | Area Under the Plasma Concentration Versus Time Curve (AUC) of Abraxane® (Phase 1 and Phase 2) - Day 1 | 5560 ng*hr/mL | Standard Deviation 2410 |
| RX-3117 + Abraxane Phase 2 | Area Under the Plasma Concentration Versus Time Curve (AUC) of Abraxane® (Phase 1 and Phase 2) - Day 1 | 5290 ng*hr/mL | Standard Deviation 2120 |
Secondary
Area Under the Plasma Concentration Versus Time Curve (AUC) of Abraxane®(Phase 1 and Phase 2) - Day 15
Time frame: Day 15 (pre-infusion, post-infusion, pre-dose RX-3117, and 0.5, 1, 2, 4, and 6 hours after administration)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RX-3117 + Abraxane Phase 1 | Area Under the Plasma Concentration Versus Time Curve (AUC) of Abraxane®(Phase 1 and Phase 2) - Day 15 | 4020 ng*hr/mL | Standard Deviation 1710 |
| RX-3117 + Abraxane Phase 2 | Area Under the Plasma Concentration Versus Time Curve (AUC) of Abraxane®(Phase 1 and Phase 2) - Day 15 | 3670 ng*hr/mL | Standard Deviation 2080 |
Secondary
Area Under the Plasma Concentration Versus Time Curve (AUC) of RX-3117 and Abraxane® (Phase 1 and Phase 2) - Day 15
Time frame: Day 15 (pre-infusion, post-infusion, pre-dose RX-3117, and 0.5, 1, 2, 4, and 6 hours after administration)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RX-3117 + Abraxane Phase 1 | Area Under the Plasma Concentration Versus Time Curve (AUC) of RX-3117 and Abraxane® (Phase 1 and Phase 2) - Day 15 | 1820 ng*hr/mL | Standard Deviation 510 |
| RX-3117 + Abraxane Phase 2 | Area Under the Plasma Concentration Versus Time Curve (AUC) of RX-3117 and Abraxane® (Phase 1 and Phase 2) - Day 15 | 3160 ng*hr/mL | Standard Deviation 1490 |
Secondary
Area Under the Plasma Concentration Versus Time Curve (AUC) of RX-3117 (Phase 1 and Phase 2) - Day 1
Time frame: Cycle 1 Day 1 (pre-infusion, post-infusion, pre-dose RX-3117, and 0.5, 1, 2, 4, 6, and 24 hours after administration)
Population: Pharmacokinetic sampling only performed in Phase 1 and Stage 1 of Phase 2. Twelve patients were dosed as a part of Stage 1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RX-3117 + Abraxane Phase 1 | Area Under the Plasma Concentration Versus Time Curve (AUC) of RX-3117 (Phase 1 and Phase 2) - Day 1 | 10500 ng*hr/mL | Standard Deviation 6490 |
| RX-3117 + Abraxane Phase 2 | Area Under the Plasma Concentration Versus Time Curve (AUC) of RX-3117 (Phase 1 and Phase 2) - Day 1 | 8780 ng*hr/mL | Standard Deviation 4460 |
Secondary
Duration of Response [DOR] (Phase 1 and Phase 2)
Duration of response is defined as the time from documentation of response to disease progression.
Time frame: Up to 32 weeks
Population: Duration of Response was not evaluable
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| RX-3117 + Abraxane Phase 1 | Duration of Response [DOR] (Phase 1 and Phase 2) | NA weeks |
| RX-3117 + Abraxane Phase 2 | Duration of Response [DOR] (Phase 1 and Phase 2) | NA weeks |
Secondary
Maximum Observed Concentration [Cmax] of Abraxane (Phase 1 and Phase 2) - Day 1
Time frame: Cycle 1 Days 1 (pre-infusion, post-infusion, pre-dose RX-3117, and 0.5, 1, 2, 4, 6, and 24 hours after administration)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RX-3117 + Abraxane Phase 1 | Maximum Observed Concentration [Cmax] of Abraxane (Phase 1 and Phase 2) - Day 1 | 4160 ng/mL | Standard Deviation 2770 |
| RX-3117 + Abraxane Phase 2 | Maximum Observed Concentration [Cmax] of Abraxane (Phase 1 and Phase 2) - Day 1 | 3940 ng/mL | Standard Deviation 2320 |
Secondary
Maximum Observed Concentration [Cmax] of Abraxane (Phase 1 and Phase 2) - Day 15
Time frame: Day 15 (pre-infusion, post-infusion, pre-dose RX-3117, and 0.5, 1, 2, 4, and 6 hours after administration)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RX-3117 + Abraxane Phase 1 | Maximum Observed Concentration [Cmax] of Abraxane (Phase 1 and Phase 2) - Day 15 | 4780 ng/mL | Standard Deviation 2380 |
| RX-3117 + Abraxane Phase 2 | Maximum Observed Concentration [Cmax] of Abraxane (Phase 1 and Phase 2) - Day 15 | 3320 ng/mL | Standard Deviation 2330 |
Secondary
Maximum Observed Concentration [Cmax] of RX-3117 (Phase 1 and Phase 2) - Day 1
Time frame: Cycle 1 Days 1 (pre-infusion, post-infusion, pre-dose RX-3117, and 0.5, 1, 2, 4, 6, and 24 hours after administration)
Population: Pharmacokinetic sampling only performed in Phase 1 and Stage 1 of Phase 2. Twelve patients were dosed as a part of Stage 1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RX-3117 + Abraxane Phase 1 | Maximum Observed Concentration [Cmax] of RX-3117 (Phase 1 and Phase 2) - Day 1 | 1120 ng/mL | Standard Deviation 516 |
| RX-3117 + Abraxane Phase 2 | Maximum Observed Concentration [Cmax] of RX-3117 (Phase 1 and Phase 2) - Day 1 | 947 ng/mL | Standard Deviation 422 |
Secondary
Maximum Observed Concentration [Cmax] of RX-3117 (Phase 1 and Phase 2) - Day 15
Time frame: Day 15 (pre-infusion, post-infusion, pre-dose RX-3117, and 0.5, 1, 2, 4, and 6 hours after administration)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RX-3117 + Abraxane Phase 1 | Maximum Observed Concentration [Cmax] of RX-3117 (Phase 1 and Phase 2) - Day 15 | 528 ng/mL | Standard Deviation 166 |
| RX-3117 + Abraxane Phase 2 | Maximum Observed Concentration [Cmax] of RX-3117 (Phase 1 and Phase 2) - Day 15 | 838 ng/mL | Standard Deviation 329 |
Secondary
Overall Response Rate [ORR] (Phase 1 and Phase 2)
Overall Response Rate will be based on the RECIST v1.1 and is defined as the percentage of subjects meeting criteria of Complete Response (CR) or Partial Response (PR). CR or PR must be confirmed at least 4 weeks after the date of the original CR or PR.
Time frame: Every 8 weeks until progression or discontinuation, whichever came first, assessed up to 32 weeks
Population: The overall number of participants analyzed is based on the modified intent-to-treat population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RX-3117 + Abraxane Phase 1 | Overall Response Rate [ORR] (Phase 1 and Phase 2) | 2 Participants |
| RX-3117 + Abraxane Phase 2 | Overall Response Rate [ORR] (Phase 1 and Phase 2) | 7 Participants |
Secondary
Progression-free Survival [PFS] (Phase 1)
Progression Free Survival defined as the percentage of subjects who are alive in the study and not in progression.
Time frame: Every 8 weeks until progression or discontinuation, whichever came first, assessed up to 32 weeks
Population: The overall number of participants analyzed is based on the modified intent-to-treat population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| RX-3117 + Abraxane Phase 1 | Progression-free Survival [PFS] (Phase 1) | 13.8 weeks |
| RX-3117 + Abraxane Phase 2 | Progression-free Survival [PFS] (Phase 1) | 23.3 weeks |
Secondary
Time to Maximum Observed Concentration [Tmax] of Abraxane® (Phase 1 and Phase 2) - Day 1
Time frame: Cycle 1 Days 1 (pre-infusion, post-infusion, pre-dose RX-3117, and 0.5, 1, 2, 4, 6, and 24 hours after administration)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RX-3117 + Abraxane Phase 1 | Time to Maximum Observed Concentration [Tmax] of Abraxane® (Phase 1 and Phase 2) - Day 1 | 0.71 hr | Standard Deviation 0.17 |
| RX-3117 + Abraxane Phase 2 | Time to Maximum Observed Concentration [Tmax] of Abraxane® (Phase 1 and Phase 2) - Day 1 | 0.62 hr | Standard Deviation 0.1 |
Secondary
Time to Maximum Observed Concentration [Tmax] of Abraxane® (Phase 1 and Phase 2) - Day 15
Time frame: Day 15 (pre-infusion, post-infusion, pre-dose RX-3117, and 0.5, 1, 2, 4, and 6 hours after administration)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RX-3117 + Abraxane Phase 1 | Time to Maximum Observed Concentration [Tmax] of Abraxane® (Phase 1 and Phase 2) - Day 15 | 0.55 hr | Standard Deviation 0.06 |
| RX-3117 + Abraxane Phase 2 | Time to Maximum Observed Concentration [Tmax] of Abraxane® (Phase 1 and Phase 2) - Day 15 | 0.69 hr | Standard Deviation 0.18 |
Secondary
Time to Maximum Observed Concentration [Tmax] of RX-3117 (Phase 1 and Phase 2) - Day 1
Time frame: Cycle 1 Days 1 (pre-infusion, post-infusion, pre-dose RX-3117, and 0.5, 1, 2, 4, 6, and 24 hours after administration)
Population: Pharmacokinetic sampling only performed in Phase 1 and Stage 1 of Phase 2. Twelve patients were dosed as a part of Stage 1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RX-3117 + Abraxane Phase 1 | Time to Maximum Observed Concentration [Tmax] of RX-3117 (Phase 1 and Phase 2) - Day 1 | 2.3 hr | Standard Deviation 0.89 |
| RX-3117 + Abraxane Phase 2 | Time to Maximum Observed Concentration [Tmax] of RX-3117 (Phase 1 and Phase 2) - Day 1 | 4.51 hr | Standard Deviation 6.18 |
Secondary
Time to Maximum Observed Concentration [Tmax] of RX-3117 (Phase 1 and Phase 2) - Day 15
Time frame: Day 15 (pre-infusion, post-infusion, pre-dose RX-3117, and 0.5, 1, 2, 4, and 6 hours after administration)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RX-3117 + Abraxane Phase 1 | Time to Maximum Observed Concentration [Tmax] of RX-3117 (Phase 1 and Phase 2) - Day 15 | 1.84 hr | Standard Deviation 0.41 |
| RX-3117 + Abraxane Phase 2 | Time to Maximum Observed Concentration [Tmax] of RX-3117 (Phase 1 and Phase 2) - Day 15 | 3.75 hr | Standard Deviation 1.35 |
Secondary
Time to Progression (Phase 2)
Time to Progression defined as the time from first treatment administration to first documentation of RECIST-defined objective tumor progression.
Time frame: Every 8 weeks until progression or discontinuation, whichever came first, assessed up to 32 weeks
Population: The overall number of participants analyzed is based on the modified intent-to-treat population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| RX-3117 + Abraxane Phase 1 | Time to Progression (Phase 2) | 13.8 weeks |
| RX-3117 + Abraxane Phase 2 | Time to Progression (Phase 2) | 23.4 weeks |
Secondary
Time to Response [TTR] (Phase 1)
Time frame: Up to 32 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| RX-3117 + Abraxane Phase 1 | Time to Response [TTR] (Phase 1) | 23.6 weeks |
Other Pre-specified
Exploratory Measurement of Protein Biomarkers Related to RX-3117 or Pancreatic Cancer (Phase 1 and 2)
Time frame: Baseline, and at 8, 6, 24, and 32 weeks
Other Pre-specified
Quality of Life (QOL) (Phase 1 and 2)
Weekly patient reported quality of life measures using validated QOL questionnaires
Time frame: 9 months
Other Pre-specified
Tumor Burden Response (Phase 2)
Changes in tumor burden response via tumor marker measurement
Time frame: Baseline, and at 8, 6, 24, and 32 weeks