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Completed

NCT Number: NCT01482715

A Study of Oral Rucaparib in Patients With a Solid Tumor (Phase I) or With gBRCA Mutation Ovarian Cancer (Phase II)

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).

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Key information

Conditions

Ovarian Cancer Adnexal Diseases Advanced Solid Tumor With Evidence of Germline or Somatic BRCA Disease Attributes Endocrine Gland Neoplasms Endocrine System Diseases Fallopian Tube Cancer Fallopian Tube Diseases Fallopian Tube Neoplasms Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Genital Diseases Genital Diseases, Female Genital Neoplasms, Female Gonadal Disorders Neoplasms Neoplasms by Site Ovarian Diseases Ovarian Neoplasms Pathologic Processes Pathological Conditions, Signs and Symptoms Peritoneal Cancer Recurrence Urogenital Diseases Urogenital Neoplasms

Age range

18 year and older

Sex eligibility

Female

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Princess Margaret Cancer Centre, Toronto, Ontario, Canada

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Rucaparib

Drug

Oral tablets administered daily with 8 oz (240 mL) of water on an empty stomach or with food; 21-day cycles of treatment. In Part 1, the initial dose level is 40 mg/day (once a day); doses and dosing frequency(e.g. twice a day or three times a day) will be adjusted until Maximum Tolerated Dose (MTD) and the Recommended Phase 2 Dose (RP2D) are established. Patients enrolled in Part 2 and Part 3 will receive the RP2D for continuous 21-day treatment cycles until disease progression.

Other names: CO-338; PF 01367338, AG 14699

Primary outcomes

  1. Overall Response Rate Per RECIST Version 1.1 (Part 2)

    Time frame: Time from first dose to date of progression, up to approximately 8 months

    The confirmed response rate by RECIST v1.1 is defined as the proportion of patients with a confirmed Complete Response (CR) or Partial Response (PR) on subsequent tumor assessment at least 28 days after first response documentation.

  2. Number of Participants With a Dose Limiting Toxicity (DLT)

    Time frame: Cycle 1 Day 1 to Cycle 1 Day 21

    The number of Part 1 (Phase 1) patients who experienced dose limiting toxicities after one cycle (21 days) of study drug.

  3. PK Profile of Rucaparib - Cmax (Part 1)

    Time frame: Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days

    Cmax = maximum concentration following administration of rucaparib

  4. PK Profile of Rucaparib - Tmax (Part 1)

    Time frame: Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days

    Tmax = time to maximum concentration following administration of rucaparib

  5. PK Profile of Rucaparib - AUC Last (Part 1)

    Time frame: Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days

    AUC last = Area under the plasma concentration-time curve from time 0 to the last recorded observation

Secondary outcomes

  1. Progression-free Survival (PFS) According to RECIST v1.1, as Assessed by the Investigator (Part 2)

    Time frame: Cycle 1 Day 1 to End of Treatment, up to approximately 51 months

    PFS is calculated as 1+ the number of days from the first dose of study drug to disease progression by RECIST, as determined by the investigator or death due to any cause, whichever occurs first.

  2. Duration of Response Per RECIST Version 1.1 (Part 2)

    Time frame: Cycle 1 Day 1 to End of Treatment, up to approximately 48 months

    Duration of response (DOR) for any confirmed RECIST CR or PR measured from the date of the first occurrence of a response until the first occurrence of PD per RECIST. For patients who continued treatment post-progression, the first date of progression was used for the analysis. Any patients with an ongoing response were censored at the date of the last post-baseline scan.

  3. Overall Survival (Part 2B)

    Time frame: Cycle 1 Day 1 to date of death, assessed up to 38 months

    Overall survival (OS) is defined as the number of days from the date of first dose of study drug to the date of death, due to any cause. Patients without a documented event of death will be censored on the date of their last visit.

  4. Food Effect on PK of Rucaparib - Cmax (Part 1 and Part 3)

    Time frame: Day -7 to Cycle 1 Day 1, or approximately 7 days

    Cmax = maximum concentration following administration of rucaparib. The effect of food on rucaparib PK parameters was assessed over a 24-hour period in blood samples from a subset of patients. Patients were given a single dose of 40 mg or 300 mg rucaparib (Part 1), or 600 mg rucaparib (Part 3) and were randomized to one of two sequences where they were either Fed (with a high-fat meal) or Fasted (without a high-fat meal) on Day -7 or Cycle 1 Day 1. On each day, patients underwent blood sampling for PK at the specified time points. The median Fed and Fasted Cmax values were calculated for each arm.

  5. Food Effect on PK of Rucaparib - Tmax (Part 1 and Part 3)

    Time frame: Day -7 to Cycle 1 Day 1, or approximately 7 days

    Tmax = time to maximum concentration following administration of rucaparib. The effect of food on rucaparib PK parameters was assessed over a 24-hour period in blood samples from a subset of patients. Patients were given a single dose of 40 mg or 300 mg rucaparib (Part 1), or 600 mg rucaparib (Part 3) and were randomized to one of two sequences where they were either Fed (with a high-fat meal) or Fasted (without a high-fat meal) on Day -7 or Cycle 1 Day 1. On each day, patients underwent blood sampling for PK at the specified time points. The median Fed and Fasted Tmax values were calculated for each arm.

  6. Food Effect on PK of Rucaparib - AUC Last (Part 1 and Part 3)

    Time frame: Day -7 to Cycle 1 Day 1, or approximately 7 days

    AUC last = Area under the plasma concentration-time curve from time 0 to the last recorded observation. The effect of food on rucaparib PK parameters was assessed over a 24-hour period in blood samples from a subset of patients. Patients were given a single dose of 40 mg or 300 mg rucaparib (Part 1), or 600 mg rucaparib (Part 3) and were randomized to one of two sequences where they were either Fed (with a high-fat meal) or Fasted (without a high-fat meal) on Day -7 or Cycle 1 Day 1. On each day, patients underwent blood sampling for PK at the specified time points. The median Fed and Fasted AUC last values were calculated for each arm.

  7. QTcF Value Change From Baseline (Part 1)

    Time frame: Screening to End of Treatment, up to approximately 15 months

    QTcF value change from baseline by daily dose corrected using Fridericia's method (QTcF). To evaluate the effects of rucaparib on the QT (interval from Q wave to T wave)/QTc (interval corrected for heart rate) interval, all patients underwent serial ECG monitoring at Screening, on Cycle 1 Day -1, Cycle 1 Day 1, Cycle 1 Day 15, Cycle 1 Day 22, on Day 1 of all subsequent cycles, at the EOT Visit, and as clinically indicated. Worst post-baseline QTcF value was used to categorize each patient.

Sponsors and collaborators

Lead sponsor

pharmaand GmbH

Industry

Collaborators

  • Foundation Medicine

Registry information

Official study 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

Important dates

Study start
2011
Primary completion
2019
Study completion
2019
First posted
Nov 30, 2011
Registry last updated
Jun 9, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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