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Ovarian CancerPhase 1/2NCT01482715

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

A Phase 1/2 study testing Rucaparib in people with Ovarian Cancer and Fallopian Tube Cancer, run by pharmaand GmbH at 16 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Rucaparib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
136 participants
Where
16 sitesin 5 countries
Study dates
Nov 2011to May 2019
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

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

Trial locations and contacts

16 sites in 5 countries.

16 sites in 5 countries

United States6 sites

  • Dana-Farber Cancer Institute (Part 3 only)

    Boston, Massachusetts, 02215

  • Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • Sarah Cannon Research Institute

    Nashville, Tennessee, 37203

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • UCSF

    San Francisco, California, 94155

  • Sarah Cannon Research Institute

    Sarasota, Florida, 34232

Other trials in United States

United Kingdom6 sites

  • Institution of Cancer Science, University of Glasgow Wolfson Wohl Cancer Research

    Glasgow, Scotland, G61 1QH

  • Guy's and St Thomas NHS Foundation Trust

    London, England, SE1 9RT

  • Royal Marsden NHS Foundation Trust

    London, England, SW3 6JJ

  • Imperial College Healthcare

    London, England, W12 0HS

  • University College London Cancer Institute

    London, WC1E 6BT

  • Newcastle University

    Newcastle upon Tyne, England, UK NE7

Other trials in United Kingdom

Israel2 sites

  • Sheba Medical Center

    Ramat Gan, 52621

  • Tel Aviv Sourasky Medical Center

    Tel Aviv, 632394

Other trials in Israel

Canada1 site

  • Princess Margaret Cancer Centre

    Toronto, Ontario, MSG 2M9

Other trials in Canada

Spain1 site

  • Hospital Vall d'Hebron

    Barcelona, 8035

Other trials in Spain

About this study

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

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).

Read the 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.

Being tested
Rucaparib
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
Medical subject headings
Ovarian Neoplasms, Fallopian Tube Neoplasms, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RucaparibDrug

    Also called CO-338; PF 01367338, AG 14699

    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.

Study groups in NCT01482715
Study groupRoleWhat they receive
Part 1 (Phase 1)ExperimentalRucaparib 40, 80, 160, 300, 500 mg QD and 240, 360, 480, 600, 840 mg BID, for continuous 21-day cycles. Patients in Part 1 were initially treated in a Dose-escalation Evaluation Period (Cycle 1) and could then continue to receive treatment in an optional Treatment-extension Period (Cycle 2 and beyond).
Receives: Drug: Rucaparib
Part 2A (Phase 2)ExperimentalRucaparib 600 mg BID for 21-day cycles.
Receives: Drug: Rucaparib
Part 2B (Phase 2)ExperimentalRucaparib 600 mg BID for 21-day cycles.
Receives: Drug: Rucaparib
Part 3 (Phase 2)ExperimentalRucaparib 600 mg BID for 21-day cycles. Patients also received a single administration of 600 mg rucaparib on both Day -7 and Day 1 for assessing the effect of food on PK.
Receives: Drug: Rucaparib

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    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.

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

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

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

    Measured: Cycle 1 Day 1 to Cycle 1 Day 21

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

    Cmax = maximum concentration following administration of rucaparib

    Measured: Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days

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

    Tmax = time to maximum concentration following administration of rucaparib

    Measured: Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days

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

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

    Measured: Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days

Secondary outcomes (7)

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

    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.

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

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

    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.

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

  3. Overall Survival (Part 2B)

    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.

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

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

    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.

    Measured: Day -7 to Cycle 1 Day 1, or approximately 7 days

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

    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.

    Measured: Day -7 to Cycle 1 Day 1, or approximately 7 days

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

    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.

    Measured: Day -7 to Cycle 1 Day 1, or approximately 7 days

  7. QTcF Value Change From Baseline (Part 1)

    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.

    Measured: Screening to End of Treatment, up to approximately 15 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Nov 2011 (estimated)
  2. Study startNov 2011
  3. Primary completionMar 2019
  4. Study completionMay 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
136 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01482715
Sponsor's protocol ID
CO-338-010
Other IDs
2011-004250-26
Status last verified
Jun 2023
First submitted
22 Nov 2011
Last updated
9 Jun 2023
Data monitoring committee
No

Publications

  • Kristeleit RS, Drew Y, Oza AM, Domchek SM, Banerjee S, Glasspool RM, Balmana J, Chen LM, Patel MR, Burris HA, Safra T, Borrow J, Lin KK, Goble S, Maloney L, Shapira-Frommer R. Efficacy and safety of rucaparib treatment in patients with BRCA-mutated, relapsed ovarian cancer: final results from Study 10. Br J Cancer. 2023 Jan;128(2):255-265. doi: 10.1038/s41416-022-02022-y. Epub 2022 Dec 8.

    PubMed 36482193

  • 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.

    PubMed 35397664

  • 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.

    PubMed 31685558

  • 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.

    PubMed 29799676

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Rucaparib in people with Ovarian Cancer and Fallopian Tube Cancer, run by pharmaand GmbH at 16 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in United States, United Kingdom, Israel, Canada, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Dec 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01482715, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jun 2023.

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