A Phase I Study to Evaluate the Safety and Efficacy of RP72 Monotherapy and in Combination With Gemcitabine in Patients With Pancreatic Cancer
Overview
- Phase
- Phase 1
- Intervention
- RP72
- Conditions
- Pancreatic Cancer
- Sponsor
- Rise Biopharmaceuticals, Inc.
- Enrollment
- 48
- Locations
- 2
- Primary Endpoint
- Determination of the maximum tolerated dose (MTD) and the recommended dose for phase II of RP72 monotherapy and RP72 in combination with Gemcitabine
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
This is a Phase I, multi center study to evaluate the safety and efficacy and determine the maximum tolerated dose (MTD) of RP72 as monotherapy and RP72 in combination with Gemcitabine in patients with pancreatic cancer.
The study has two arms:
Arm A: RP72 monotherapy
Arm B: RP72 in combination with Gemcitabine
Both treatment arms will follow a standard 3+3 design. Up to 48 adult patients with pancreatic cancer will be enrolled in this study.
Detailed Description
RP72 (Rise Prot-72) is a small molecular weight protein which directly binds to CXCR1 and CXCR2, which are the receptors of CXCL8 \[Interleukin 8 (IL-8) or chemokine (C-X-C motif) ligand 8\] and ELR-CXC chemokine. Therefore, RP72 can inhibit the binding of CXCL8 to its receptors CXCR1/2 and further block CXCL8-mediated signal transduction. Nonclinical studies have demonstrated that RP72 binds to the receptors of CXCL8 and blocks activation of CXCL8-mediated signaling transduction pathways, which decreases proliferation of susceptible tumor cells, especially the pancreatic cancer cells. In this Phase I study, RP-72 will be used as monotherapy or in combination with gemcitabine in adult patients with pancreatic cancer. The study aims to to evaluate the safety and efficacy, and to determine the MTD and recommended Phase II dose of RP72 monotherapy and RP72 in combination with Gemcitabine in patients with Pancreatic Cancer.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age ≥ 18 years (in certain territories, the minimum age requirement may be higher, e.g. age ≥ 20 years in Taiwan)
- •Written informed consent
- •Patient must meet one of the following criteria based on:
- •Arm A (RP72 monotherapy): Histologically or cytologically confirmed locally advanced unresectable or metastatic pancreatic cancer that has progressed on (or intolerant of) one or more standard treatment regimen(s) or for which no effective therapy is available. Note: Prior exposure to gemcitabine as a single agent or in combination with other agents (as part of multi-agent chemotherapy regimen) is acceptable.
- •Arm B (RP72 in combination with Gemcitabine): Histologically or cytologically confirmed locally advanced unresectable or metastatic pancreatic cancer that has progressed on (or intolerant of) one or more standard treatment regimen(s) and is expected (or currently receiving) standard treatment with gemcitabine.Note: Patients who have already started on gemcitabine need to have no evidence of disease progression at the time of screening in order to be eligible for the study.
- •Note: The definition of unresectability will follow the criteria of NCCN guidelines (Carroll et al. version 2.2016, PANC-B)
- •Fasting blood glucose \<160 mg/dl, prior to study enrollment. (For higher values, blood glucose may be controlled by dietary intervention, oral hypoglycemics and/ or insulin prior to enrollment)
- •Estimated life expectancy of ≥12 weeks
- •Adequate hematologic and end-organ function
- •Measurable / assessable disease according to RECIST v.1.1
Exclusion Criteria
- •Patients with endocrine or acinar pancreatic carcinoma.
- •Patients who present with jaundice; Note: Patients who present with jaundice will be allowed to enroll after control with temporary or permanent internal/external drainage.
- •Any severe infection, uncontrolled systemic disease (e.g., cardiopulmonary insufficiency, fatal arrhythmias, hepatitis, etc) that, in the opinion of the investigator, may impair the patient's tolerance of study treatment.
- •Major surgery within 4 weeks from the first dose of the study drug
- •Female subjects that are lactating, pregnant, or planned to become pregnant
- •Investigational medicinal product within 4 weeks or less than 5 half-life periods (whichever is shorter) from the first dose of the study drug
- •Concurrent use of immunosuppressive medication. The following are exceptions to this criterion:
- •Intranasal, inhaled, topical steroids, or local steroid injections
- •Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
- •Steroids as premedication for hypersensitivity reactions
Arms & Interventions
Arm A: RP72 monotherapy
Intervention: RP72
Arm B: RP72 in combination with Gemcitabine
Intervention: RP72
Arm B: RP72 in combination with Gemcitabine
Intervention: Gemcitabine
Outcomes
Primary Outcomes
Determination of the maximum tolerated dose (MTD) and the recommended dose for phase II of RP72 monotherapy and RP72 in combination with Gemcitabine
Time Frame: Over the 28 day treatment period
The MTD is defined as 1 dose level (cohort) below the dose in which dose limiting toxicities (DLTs) were observed in ≥ 33% of the participants.