Clinical trial NCT01482715: A Study of Oral Rucaparib in Patients With a Solid Tumor (Phase I) or With gBRCA Mutation Ovarian Cancer (Phase II)
Official title: A Phase I/II, Open-Label, Safety, Pharmacokinetic, and Preliminary Efficacy Study of Oral Rucaparib in Patients With gBRCA Mutation Ovarian Cancer or Other Solid Tumor
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Ovarian Cancer
Fallopian Tube Cancer
Peritoneal Cancer
Advanced Solid Tumor With Evidence of Germline or Somatic BRCA
Keywords: gBRCA ovarian cancer
platinum sensitive
PARP Inhibitor
Rucaparib
CO-338
PF 01367338
AG 14699
BRCA1
BRCA2
platinum sensitive ovarian cancer
platinum sensitive gBRCA ovarian cancer
gynecological cancer
relapsed disease
homologous recombination deficiency
HRD
Lead sponsor: pharmaand GmbH
Sponsor class: INDUSTRY
Collaborators: name: Foundation Medicine
First posted: 2011-11-30
Enrollment: 136
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: Part 1 (Completed Enrollment) - The purpose of the first part of the study was to evaluate the safety of different doses and dosing regimens of oral rucaparib administered daily to patients with solid tumors.

Part 2A (Completed Enrollment) and Part 2B (Completed Enrollment) - The purpose of the second part of the study is to determine the safety and clinical activity of the RP2D of oral rucaparib administered daily to patients with a known deleterious BRCA mutation (germline or somatic).

Part 3 (Completed Enrollment) - The purpose of the third part of the study is to further evaluate PK of higher dose strength tablets at the RP2D in patients with any advanced solid tumor, inclusive of lymphoma, with evidence of a BRCA mutation (germline or somatic).

Detailed description: Rucaparib (CO-338; formerly known as PF 01367338 and AG 14699) is an orally available, small molecule inhibitor of poly-adenosine diphosphate \[ADP\] ribose polymerase (PARP) being developed for treatment of ovarian cancer associated with homologous recombination \[HR\] DNA repair deficiency (HRD). The safety and efficacy of rucaparib has been evaluated in several Phase 1 and Phase 2 studies.

An oral formulation is the focus of current development efforts. Rucaparib is currently being investigated as monotherapy in patients with cancer associated with BRCA1 or BRCA2 mutations. For this study, it is anticipated that rucaparib will promote cell death in the BRCA-deficient tumor cells of ovarian cancer patients with evidence of a germline mutation, thereby limiting tumor progression and providing therapeutic benefit.

Eligibility criteria: The following eligibility criteria below pertain to patients enrolling into Part 2B of the study.

Inclusion Criteria:

* Have a known deleterious BRCA mutation (gBRCA or sBRCA) (as determined by a local laboratory that has received an international or country-specific, quality standards certification)
* Have evidence of measurable disease as defined by RECIST Version 1.1
* Have sufficient archival FFPE tumor tissue available for planned analyses. Archival tissue from the most recently collected biopsy or debulking surgery should be provided, if available.
* Have a histologically confirmed diagnosis of high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer
* Have received at least three prior chemotherapy regimens and have relapsed disease confirmed by radiologic assessment

Exclusion Criteria:

* Active second malignancy, i.e., patient known to have potentially fatal cancer present for which she may be (but not necessarily) currently receiving treatment

  a. Patients with a history of malignancy that has been completely treated, with no evidence of that cancer currently, are permitted to enroll in the trial provided all chemotherapy was completed \>6 months prior and/or bone marrow transplant (BMT) \>2 years prior to first dose of rucaparib
* Prior treatment with any PARP inhibitor.
* Untreated or symptomatic central nervous system (CNS) metastases. Patients with asymptomatic CNS metastases are eligible provided they have been clinically stable for at least 4 weeks.
* Received treatment with chemotherapy, radiation, antibody therapy or other immunotherapy, gene therapy, vaccine therapy, angiogenesis inhibitors, or experimental drugs 14 days prior to first dose of rucaparib and/or ongoing adverse effects from such treatment \> NCI CTCAE Grade 1 (Grade 2 non-hematologic toxicity to most recent treatment may be permitted with prior advanced approval from Sponsor).
* Hospitalization for bowel obstruction within 3 months prior to enrollment.

Primary outcomes:
measure: Overall Response Rate Per RECIST Version 1.1 (Part 2)
timeFrame: Time from first dose to date of progression, up to approximately 8 months
measure: Number of Participants With a Dose Limiting Toxicity (DLT)
timeFrame: Cycle 1 Day 1 to Cycle 1 Day 21
measure: PK Profile of Rucaparib - Cmax (Part 1)
timeFrame: Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days
measure: PK Profile of Rucaparib - Tmax (Part 1)
timeFrame: Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days
measure: PK Profile of Rucaparib - AUC Last (Part 1)
timeFrame: Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days
Secondary outcomes:
measure: Progression-free Survival (PFS) According to RECIST v1.1, as Assessed by the Investigator (Part 2)
timeFrame: Cycle 1 Day 1 to End of Treatment, up to approximately 51 months
measure: Duration of Response Per RECIST Version 1.1 (Part 2)
timeFrame: Cycle 1 Day 1 to End of Treatment, up to approximately 48 months
measure: Overall Survival (Part 2B)
timeFrame: Cycle 1 Day 1 to date of death, assessed up to 38 months
measure: Food Effect on PK of Rucaparib - Cmax (Part 1 and Part 3)
timeFrame: Day -7 to Cycle 1 Day 1, or approximately 7 days
measure: Food Effect on PK of Rucaparib - Tmax (Part 1 and Part 3)
timeFrame: Day -7 to Cycle 1 Day 1, or approximately 7 days
measure: Food Effect on PK of Rucaparib - AUC Last (Part 1 and Part 3)
timeFrame: Day -7 to Cycle 1 Day 1, or approximately 7 days
measure: QTcF Value Change From Baseline (Part 1)
timeFrame: Screening to End of Treatment, up to approximately 15 months
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: UCSF
state: California
city: Sarasota
country: United States
facility: Sarah Cannon Research Institute
state: Florida
city: Boston
country: United States
facility: Dana-Farber Cancer Institute (Part 3 only)
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: London
country: United Kingdom
facility: Guy's and St Thomas NHS Foundation Trust
state: England
city: London
country: United Kingdom
facility: Royal Marsden NHS Foundation Trust
state: England
city: London
country: United Kingdom
facility: Imperial College Healthcare
state: England
city: Newcastle Upon Tyne
country: United Kingdom
facility: Newcastle University
state: England
city: Glasgow
country: United Kingdom
facility: Institution of Cancer Science, University of Glasgow Wolfson Wohl Cancer Research
state: Scotland
city: London
country: United Kingdom
facility: University College London Cancer Institute
Study officials:
References:
citation: Green ML, Ma SC, Goble S, Giordano H, Maloney L, Simmons AD, Beltman J, Harding TC, Xiao JJ. Population pharmacokinetics of rucaparib in patients with advanced ovarian cancer or other solid tumors. Cancer Chemother Pharmacol. 2022 May;89(5):671-682. doi: 10.1007/s00280-022-04413-7. Epub 2022 Apr 10.
citation: Kristeleit RS, Oaknin A, Ray-Coquard I, Leary A, Balmana J, Drew Y, Oza AM, Shapira-Frommer R, Domchek SM, Cameron T, Maloney L, Goble S, Lorusso D, Ledermann JA, McNeish IA. Antitumor activity of the poly(ADP-ribose) polymerase inhibitor rucaparib as monotherapy in patients with platinum-sensitive, relapsed, BRCA-mutated, high-grade ovarian cancer, and an update on safety. Int J Gynecol Cancer. 2019 Nov;29(9):1396-1404. doi: 10.1136/ijgc-2019-000623.
citation: Shapiro GI, Kristeleit RS, Burris HA, LoRusso P, Patel MR, Drew Y, Giordano H, Maloney L, Watkins S, Goble S, Jaw-Tsai S, Xiao JJ. Pharmacokinetic Study of Rucaparib in Patients With Advanced Solid Tumors. Clin Pharmacol Drug Dev. 2019 Jan;8(1):107-118. doi: 10.1002/cpdd.575. Epub 2018 May 25.