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

NCT03140670 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: UPCC 05217
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

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.

Conditions

Pancreatic Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Overall Survival

  24 months

• Overall Response Rate (ORR)

  24 months

• Disease Control Rate (DCR)

  24 months

• Duration of Response (DOR)

  24 months

• Toxicity at Least Possibly Related to Rucaparib

  24 months

Study Arms (1)

Single Arm

EXPERIMENTAL

Drug: RUCAPARIB

Interventions

RUCAPARIB DRUG

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.

Single Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Abramson Cancer Center at Penn Medicine: lead

Study Sites (1)

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (2)

• Brown TJ, Yablonovitch A, Till JE, Yen J, Kiedrowski LA, Hood R, O'Hara MH, Teitelbaum U, Karasic TB, Schneider C, Carpenter EL, Nathanson K, Domchek SM, Reiss KA. The Clinical Implications of Reversions in Patients with Advanced Pancreatic Cancer and Pathogenic Variants in BRCA1, BRCA2, or PALB2 after Progression on Rucaparib. Clin Cancer Res. 2023 Dec 15;29(24):5207-5216. doi: 10.1158/1078-0432.CCR-23-1467.

  PMID: 37486343 DERIVED

• 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.

  PMID: 33970687 DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

rucaparib

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Pancreas Research Program Manager
• Organization: Abramson Cancer Center

mazali@pennmedicine.upenn.edu

2672575567

Study Officials

• Kim Reiss Binder, MD

  Abramson Cancer Center at Penn Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 3, 2017
• First Posted: May 4, 2017
• Study Start: September 5, 2017
• Primary Completion: October 29, 2020
• Study Completion: August 7, 2023
• Last Updated: September 28, 2023
• Results First Posted: September 28, 2023

Record last verified: 2023-09

Locations

US (1)