Maintenance Rucaparib in BRCA1, BRCA2 or PALB2 Mutated Pancreatic Cancer That Has Not Progressed on Platinum-based Therapy

Study Overview
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Brief Summary
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The main purpose of this study is to look at the effectiveness, safety, and antitumor activity (preventing growth of the tumor) of the experimental study drug rucaparib (also known as CO-338) on subjects and on their pancreatic cancer.

Official Title
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A Phase 2, Open Label Study of Rucaparib in Patients With Advanced Pancreatic Cancer and a Known Deleterious Germline or Somatic BRCA or PALB2 Mutation

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: RUCAPARIB


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed diagnosis of pancreatic adenocarcinoma with locally advanced or metastatic disease ≥18 years of age. Eastern Cooperative Oncology (ECOG) performance status of 0 to 1. Patients may have previously failed non-platinum containing therapy or may never have previously progressed on treatment. Patients must be on treatment with platinum-based (cisplatin, oxaliplatin or carboplatin) treatment for locally advanced or metastatic pancreatic cancer and have received a minimum of 16 weeks of therapy without evidence of disease progression based on the investigator's opinion. Discontinuation of the platinum component of the regimen for chemotherapy-related toxicity is permissible provided the patient has previously received at least 16 weeks of platinum-based therapy without evidence of disease progression ≤8 weeks after treatment with the platinum agent Documented deleterious BRCA1/2 or PALB2 mutation (germline or somatic) as assessed by CLIA certified laboratory. Variants that are considered to be non-detrimental (Variants of uncertain significance, Variants of unknown significance, Variant, favor polymorphism or benign polymorphism etc) are not sufficient for study entry. Measurable disease is not required for enrollment. Adequate organ function confirmed by the following laboratory values obtained ≤7 days prior to the first day of rucaparib: Absolute neutrophil count (ANC) ≥1.5 x 109/L Platelets>100 x 109/L Hemoglobin≥9g/dL Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 x upper limit of normal (ULN) Total bilirubin ≤1.5 x ULN; if liver metastases or metabolic disorder such as Gilbert's syndrome, then ≤2.5 x ULN. Serum creatinine ≤1.5 x ULN or estimated glomerular filtration rate (GFR) ≥45 mL/min using Cockcroft Gault formula. Exclusion Criteria Prior treatment with a PARP inhibitor Patients who have demonstrated resistance to platinum agents (e.g. oxaliplatin, cisplatin) are not eligible to participate in this study Clinical evidence of uncontrolled malabsorption and/or any other gastrointestinal disorder or defect that would, in the opinion of the investigator, interfere with the absorption of rucaparib Acute infection requiring intravenous antibiotics, antiviral or antifungal agents during the 14 days prior to first dose of rucaparib Symptomatic or untreated CNS metastases. Expected life expectancy of <12 weeks as determined by the investigator. For fertile patient (female able to become pregnant or male able to father a child), refusal to use effective contraception during the period of the trial and for 6 months after the last dose of rucaparib. Received any systemic treatment for pancreatic cancer ≤14 days prior to first dose of rucaparib. Non-study related minor surgical procedure ≤5 days, or major surgical procedure ≤21 days, prior to the first dose of rucaparib; in all cases, patients must be sufficiently recovered and stable before treatment administration. Active drug or alcohol use or dependence that would interfere with study compliance. Presence of any other condition that may increase the risk associated with study participation or may interfere with the interpretation of study results, and, in the opinion of the investigator, would make the patient inappropriate for entry into the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Arm<br> | Drug: RUCAPARIB<br>* Rucaparib is a PARP inhibitor used as an anti-cancer agent. Rucaparib is a first-in-class pharmaceutical drug targeting the DNA repair enzyme poly-ADP ribose polymerase-1.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) at 6 Months (PFS6) | Time from initiation of rucaparib until progression or death from any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Only if absolute increase is equal to or greater than 5mm. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Time from initiation of rucaparib until death or last follow-up | 24 months | 
| Overall Response Rate (ORR) | Confirmed Complete Response or Partial Response according to RECIST v1.1. Complete Response (CR) is defined as tumor burden reduced to 0.0 mm or lymph node lesions are smaller than 10mm. Partial Response (PR), tumor burden decreased by greater than 30% but not CR. Overall Response Rate (ORR) is defined as confirmed CR or PR. | 24 months | 
| Disease Control Rate (DCR) | Confirmed complete response, partial response, or stable disease lasting for at least 16 weeks | 24 months | 
| Duration of Response (DOR) | Time from initial response to progression or death from any cause | 24 months | 
| Toxicity at Least Possibly Related to Rucaparib | Toxicity of rucaparib as maintenance therapy was assessed by examining Adverse Events (AEs) that were at least possibly related to the drug treatment. AEs were classified and graded according to the NCI Common Terminology Criteria of Adverse Events, version 4.1. | 24 months |