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brca1 Mutation CarrierPhase 2NCT00664781

Rucaparib(CO-338;Formally Called AG-014699 or PF-0136738) in Treating Patients With Locally Advanced or Metastatic Breast Cancer or Advanced Ovarian Cancer

A Phase 2 study testing rucaparib (CO-338; formally AG-014699 or PF-01367338), protein expression analysis and western blotting in people with brca1 Mutation Carrier and brca2 Mutation Carrier, run by Cancer Research UK at 7 sites in United Kingdom.

Completed

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

Official record
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Trial summary

RATIONALE: rucaparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase II trial is studying the side effects and best dose of rucaparib and to see how well it works in treating patients with locally advanced or metastatic breast cancer or advanced ovarian… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
rucaparib (CO-338; formally AG-014699 or PF-01367338), protein expression analysis and western blotting
How many people
78 participants
Where
7 sitesUnited Kingdom
Study dates
Dec 2007to Jan 2015
Phase
Phase 2
Are there results?
None posted in the registry

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
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • All stages of the study (IV and oral):
  • Patients must be proven known carriers of a mutation of BRCA1 or BRCA2 or considered to be highly likely to be carriers of a BRCA1 or 2 mutation (score of ≥ 20 as per Manchester criteria) and have histologically documented locally advanced or metastatic breast cancer or advanced ovarian cancer.
  • Patients considered highly likely to be carriers will be tested after consenting and a BRCA1 or 2 mutation must be confirmed for the patient to be eligible to receive treatment.
  • Oral stage 1 only:
  • In addition to the above, patients with high grade serous ovarian cancer with unknown BRCA status may be entered into oral stage 1.
  • Patients with ovarian cancer (including epithelial, fallopian tube cancer and primary peritoneal cancer) who have had no more than 5 prior chemotherapy regimens in the last 5 years. For the BRCA carriers > 2 months must have elapsed since their last treatment with a carboplatin- or cisplatin-containing regimen or for high grade serous ovarian cancer patients ≥ 6 months.
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  • Patients with breast cancer who have had no more than 5 prior chemotherapy regimens in the last 5 years.
  • Measurable disease as measured by X-ray, computerised tomography (CT), or MRI scan as defined by RECIST criteria. These measurements must be done within 4 weeks of the patient going on study. Clinical measurements must be done within one week of the patient going on study. Patients with bone disease must have other measurable disease for evaluation. Previously irradiated lesions cannot be used for measurable disease.
  • Life expectancy of at least 12 weeks
  • World Health Organisation (WHO) performance status of 0 or 1 (Appendix 1)
  • Haematological and biochemical indices within the ranges shown below. These measurements must be performed within one week before the patient goes on study.
  • Lab Test Value Required Haemoglobin (Hb) ≥9.0 g/dl Neutrophils ≥1.5 x 10^9/L Platelets (Plts) ≥100 x 10^9/L Serum bilirubin ≤1.5 x upper normal limit Alanine amino-transferase (ALT) and/or ≤ 2.5 x upper limit of normal (ULN) aspartate amino-transferase (AST) unless due to tumour in which case up to 5 x ULN is permissible Glomerular Filtration Rate (GFR) calculated either by the Wright formula ≥50 ml/min or Cockcroft-Gault formula or by isotope clearance measurement
  • 18 years or over
  • Written (signed and dated) informed consent and be capable of co-operating with treatment and follow-up

Who cannot join

  • Radiotherapy (except for palliative reasons), endocrine therapy, immunotherapy, chemotherapy, biological agents or investigational agents during the previous 4 weeks (6 weeks for nitrosoureas and Mitomycin-C) before treatment.
  • Ongoing toxic manifestations of previous treatments. Exceptions to this are alopecia or certain Grade 1 toxicities, which in the opinion of the Investigator and the Drug Development Office (DDO) should not exclude the patient.
  • Known brain metastases.
  • Female patients able to become pregnant (or already pregnant or lactating). However, those female patients who have a negative serum or urine pregnancy test before enrolment and agree to use two highly effective forms of contraception (oral, injected or implanted hormonal contraception and condom, have an intrauterine device and condom, diaphragm with spermicidal gel and condom, or are surgically sterilised) 4 weeks before entering the trial, during the trial and for 6 months afterwards are considered eligible.
  • Male patients with partners of child-bearing potential (unless they agree to use one form of highly effective contraception such as a barrier method of condom plus spermicide during the trial and for 6 months afterwards).
  • Major thoracic and/or abdominal surgery in the preceding 4 weeks from which the patient has not recovered.
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  • At high medical risk because of non-malignant systemic disease including active uncontrolled infection.
  • Concurrent malignancies at other sites, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin and concurrent breast and ovarian carcinoma. Cancer survivors, who have undergone potentially curative therapy for a prior malignancy, are eligible for the study.
  • Patients with active or unstable cardiac disease or history of myocardial infarction within 6 months. Patients with cardiovascular signs or symptoms should have a MUGA scan or echocardiogram, and those patients with left ventricular ejection fraction (LVEF) below the institutional limit of normal should be excluded.
  • Any other condition which in the Investigator's opinion would not make the patient a good candidate for the clinical trial.
  • Patients who have already received a PARP inhibitor.

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

United Kingdom7 sites

  • Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust

    Birmingham, England, B15 2TT

  • Beatson West of Scotland Cancer Centre

    Glasgow, Scotland, G12 0YN

  • Leeds Cancer Centre at St. James's University Hospital

    Leeds, England, LS9 7TF

  • Cancer Research UK and University College London Cancer Trials Centre

    London, England, W1T 4TJ

  • Christie Hospital

    Manchester, England, M20 4BX

  • Sir Bobby Robson Cancer Trials Research Centre, Northern Centre for Cancer Care, Level 2, Freeman Hospital

    Newcastle upon Tyne, England, NE4 6BE

  • Derriford Hospital

    Plymouth, England, PL6 8DH

Other trials in United Kingdom

About this study

Official title: A Cancer Research UK Phase II Proof of Principle Trial of the Activity of the PARP-1 Inhibitor, AG-014699, in Known Carriers of a BRCA 1 or BRCA 2 Mutation With Locally Advanced or Metastatic Breast or Advanced Ovarian Cancer

RATIONALE: rucaparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase II trial is studying the side effects and best dose of rucaparib and to see how well it works in treating patients with locally advanced or metastatic breast cancer or advanced ovarian cancer.

Read the detailed description

OBJECTIVES:

Primary

  • Assessment of Anti tumour activity to PARP-1 inhibitor rucaparib in patients with locally advanced or metastatic breast or advanced ovarian cancer shown to express the BRCA 1 or 2 mutations.
  • To evaluate the toxicity of treatment with Rucaparib in these population's.

Secondary

  • To evaluate the time to progression and overall survival in patients treated with this drug.
  • To study pharmacokinetics of this drug in these patient populations.
  • To evaluate the Poly(ADP-ribose) polymerase (PARP) activity in peripheral blood lymphocytes from BRCA 1 and 2 heterozygotic patients.
  • To determine a tolerable and effective dosing regimen of the Rucaparib oral formulation.

OUTLINE: This is a dose-escalation study followed by an open label multicenter study. The study was originally set up with an IV formulation. An oral formulation of the PARP-1 inhibitor rucaparib will be used from now on. Patients are stratified according to tumor type (breast vs ovarian) and mutation status ( BRCA 1 vs BRCA 2). In addition, patient with high-grade serous ovarian cancer can be enrolled into Stage 1 of the study. All patients enrolled will receive PARP-1 inhibitor rucaparib oral formulation once daily for either 7, 14, or 21 days of each cycle, (two possible dosages for 21 days treatment). Treatment repeats every 21 days for 12 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve stable or responding disease may receive additional courses of treatment at the discretion of the chief investigator or Drug Development Office (DDO).

Patients undergo blood sample collection periodically for pharmacokinetic and pharmacodynamic studies. Samples are analyzed for tumor marker (CA 125 and/or CA 15.3) measurements, rucaparib plasma levels via liquid chromatography/mass spectrometry/mass spectrometry, PARP activity, and PARP protein expression via western blotting immunoassays. Paraffin embedded sections from original diagnostic biopsy are also collected and analyzed for PARP protein expression via immunohistochemical technique. Pleural and ascitic fluid may be collected and analyzed for DNA DS break repair proficiency via immunohistochemical technique. Some patients also undergo biopsy of tumors and samples are analyzed for BRCA 2 mutation as well as PARP activity via validated PARP immunoblotting assay.

After completion of study treatment, patients are followed for 28 days.

Peer Reviewed and Funded or Endorsed by Cancer Research UK.

Being tested
rucaparib (CO-338; formally AG-014699 or PF-01367338), protein expression analysis, western blotting, immunohistochemistry staining method, liquid chromatography
Keywords
stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer, stage IV breast cancer, recurrent breast cancer, stage IV ovarian epithelial cancer, recurrent ovarian germ cell tumor, stage IV ovarian germ cell tumor, ovarian stromal cancer, ovarian sarcoma, BRCA1 mutation carrier, BRCA2 mutation carrier, stage IIIA ovarian epithelial cancer, stage IIIA ovarian germ cell tumor, stage IIIB ovarian epithelial cancer, stage IIIB ovarian germ cell tumor, stage IIIC ovarian epithelial cancer, stage IIIC ovarian germ cell tumor, ovarian papillary serous carcinoma
Medical subject headings
Breast Neoplasms, Ovarian Neoplasms, Carcinoma, Ovarian Epithelial

What participants receive

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

What is being measured

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

  1. Assessment of antitumor activity according to RECIST using tumor size measured clinically or radiologically with CT scan, MRI, plain x-ray, or other imaging techniques

  2. Safety profile

Secondary outcomes (4)

  1. Time to progression and overall survival

  2. Plasma levels measured by Liquid Chromatography/Mass Spectrometry/Mass Spectrometry

  3. Poly(ADP-ribose) polymerase (PARP) activity measured ex vivo using validated assays

  4. To determine the optimal oral dosing regimen, based on the assessment of antitumor activity and the safety profile

Timeline

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

  1. First posted23 Apr 2008 (estimated)
  2. Study startDec 2007
  3. Primary completionJan 2015
  4. Study completionJan 2015

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 2
Primary purpose
Treatment
Masking
None (open label)
Enrolment
78 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00664781
Sponsor's protocol ID
CDR0000593558
Other IDs
CRUK-PH2-052, CRUK-PARP/BRCA, EU-20842, EUDRACT-2006-002348-27
Status last verified
May 2016
First submitted
22 Apr 2008
Last updated
24 May 2016
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing rucaparib (CO-338; formally AG-014699 or PF-01367338), protein expression analysis and western blotting in people with brca1 Mutation Carrier and brca2 Mutation Carrier, run by Cancer Research UK at 7 sites in United Kingdom.

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 14 inclusion and 11 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 24 May 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United Kingdom. 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 phase mean?

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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Assessment of antitumor activity according to RECIST using tumor size measured clinically or radiologically with CT scan, MRI, plain x-ray, or other imaging techniques. The study lists 2 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 NCT00664781.

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 24 May 2016.

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