Clinical trial NCT03140670: Maintenance Rucaparib in BRCA1, BRCA2 or PALB2 Mutated Pancreatic Cancer That Has Not Progressed on Platinum-based Therapy
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Pancreatic Cancer
Lead sponsor: Abramson Cancer Center at Penn Medicine
Sponsor class: OTHER
First posted: 2017-05-04
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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:

  1. Absolute neutrophil count (ANC) ≥1.5 x 109/L
  2. Platelets\>100 x 109/L
  3. Hemoglobin≥9g/dL
  4. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 x upper limit of normal (ULN)
  5. Total bilirubin ≤1.5 x ULN; if liver metastases or metabolic disorder such as Gilbert's syndrome, then ≤2.5 x ULN.
  6. 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.

Primary outcomes:
measure: Progression-Free Survival (PFS) at 6 Months (PFS6)
timeFrame: 6 months
Secondary outcomes:
measure: Overall Survival
timeFrame: 24 months
measure: Overall Response Rate (ORR)
timeFrame: 24 months
measure: Disease Control Rate (DCR)
timeFrame: 24 months
measure: Duration of Response (DOR)
timeFrame: 24 months
measure: Toxicity at Least Possibly Related to Rucaparib
timeFrame: 24 months
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Abramson Cancer Center of the University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: Abramson Cancer Center at Penn Medicine
name: Kim Reiss Binder, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Reiss KA, Mick R, O'Hara MH, Teitelbaum U, Karasic TB, Schneider C, Cowden S, Southwell T, Romeo J, Izgur N, Hannan ZM, Tondon R, Nathanson K, Vonderheide RH, Wattenberg MM, Beatty G, Domchek SM. Phase II Study of Maintenance Rucaparib in Patients With Platinum-Sensitive Advanced Pancreatic Cancer and a Pathogenic Germline or Somatic Variant in BRCA1, BRCA2, or PALB2. J Clin Oncol. 2021 Aug 1;39(22):2497-2505. doi: 10.1200/JCO.21.00003. Epub 2021 May 10.