A Phase 1/2 Open-Label, Safety, Pharmacokinetic, Pharmacodynamic and Efficacy Study of RX-3117 in Combination With Abraxane® in Subjects With Metastatic Pancreatic Cancer
Overview
- Phase
- Phase 1
- Intervention
- RX-3117
- Conditions
- Metastatic Pancreatic Cancer
- Sponsor
- Processa Pharmaceuticals
- Enrollment
- 46
- Locations
- 1
- Primary Endpoint
- Number of Participants With Vital Sign Abnormalities (Phase 1 and 2)
- Status
- Completed
- Last Updated
- 2 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Disease Related
- •Subject has confirmed histologic or cytologic evidence of metastatic pancreatic cancer and has no prior treatment for metastatic pancreatic cancer.
- •Subject has measurable disease using Response Evaluation Criteria in Solid Tumors (RECIST) v 1.
- •Subject has a life expectancy of at least 3 months.
- •Subject has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or
- •Demographic
- •Males or females ≥ 18 years of age
- •Subject must be able to swallow capsules
- •Subject must have adequate venous access for intravenous (IV) infusion
- •Subject has hemoglobin ≥ 9.0 g/dL at Screening
Exclusion Criteria
- •Disease Related
- •Subject has primary brain tumors or clinical evidence of active brain metastasis
- •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
- •Subject has a history of systemic corticosteroid use within 7 days before Day 1 of Cycle 1
- •Subject has an active infection requiring parenteral or oral antibiotics within 2 weeks before planned start of study therapy
- •Subject has uncontrolled diabetes as assessed by the investigator
- •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
- •Subject has an active infection of hepatitis B, hepatitis C or human immunodeficiency virus
- •Female subjects who are pregnant, planning a pregnancy or breast feeding during the study
Arms & Interventions
RX-3117 + Abraxane
RX-3117: oral, 500 - 700 mg/ day for 5 days on/ 2 days off for 3 weeks. 1 washout week/ cycle. Abraxane: 75 - 125 mg/m\^2, infused once per week for 3 weeks. 1 washout week/ cycle.
Intervention: RX-3117
Outcomes
Primary Outcomes
Number of Participants With Vital Sign Abnormalities (Phase 1 and 2)
Time Frame: 9 months
Number of participants with clinically significant vital sign abnormalities (Phase 1 and 2) including heart rate, respiration rate, and blood pressure
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 (Phase 1 and 2)
Time Frame: 9 months
Number of participants who experienced a treatment-related adverse event
Number of Participants With Clinical Laboratory Abnormalities (Phase 1 and 2)
Time Frame: 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 Electrocardiogram (ECG) Abnormalities (Phase 1 and 2)
Time Frame: 1 month
Number of participants with clinically significant ECG abnormalities (Phase 1 and 2)
Number of Dose-limiting Toxicities (DLTs) (Phase 1)
Time Frame: 4 weeks
Number of Participants With Progression Free Survival (PFS) and/or Objective Clinical Response (Phase 2)
Time Frame: 9 months
Participants must have progression Free Survival (PFS) \> 4 months or objective clinical response (complete or partial response).
Secondary Outcomes
- 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))
- 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)
- Time to Response [TTR] (Phase 1)(Up to 32 weeks)
- Duration of Response [DOR] (Phase 1 and Phase 2)(Up to 32 weeks)
- Progression-free Survival [PFS] (Phase 1)(Every 8 weeks until progression or discontinuation, whichever came first, assessed up to 32 weeks)
- Time to Progression (Phase 2)(Every 8 weeks until progression or discontinuation, whichever came first, assessed up to 32 weeks)
- 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))
- 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))
- 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))
- 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))
- 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))