Rucaparib(CO-338;Formally Called AG-014699 or PF-0136738) in Treating Patients With Locally Advanced or Metastatic Breast Cancer or Advanced Ovarian Cancer | Completed
Rucaparib(CO-338;Formally Called AG-014699 or PF-0136738) in Treating Patients With Locally Advanced or Metastatic Breast Cancer or Advanced Ovarian Cancer
Health Conditions
  • brca1 Mutation Carrier
  • brca2 Mutation Carrier
  • Breast Cancer
  • Ovarian Cancer
Completed
Recruitment Status
NCT00664781
Primary Trial ID Number
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 cancer.
Primary Outcome Measures
  • 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; null; Safety profile; null
Secondary Outcome Measures
  • Time to progression and overall survival; null; Plasma levels measured by Liquid Chromatography/Mass Spectrometry/Mass Spectrometry; null; Poly(ADP-ribose) polymerase (PARP) activity measured ex vivo using validated assays; null; To determine the optimal oral dosing regimen, based on the assessment of antitumor activity and the safety profile; null
Research Question
  • 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.
Design Type
Sorry, this information is not available
Ethics Approval
Sorry, this information is not available
Publications
Sorry, this information is not available
Countries of Recruitment
United Kingdom
Participant Sex
Both
Participant Age Range
18 Years to N/A
Participant Type
Sorry, this information is not available
Trial Sample Size
Sorry, this information is not available
Participant Inclusion Criteria
  • INCLUSION CRITERIA
  • 1. 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.
  • 2. 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.
  • 3. Patients with breast cancer who have had no more than 5 prior chemotherapy regimens
  • in the last 5 years.
  • 4. 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.
  • 5. Life expectancy of at least 12 weeks
  • 6. World Health Organisation (WHO) performance status of 0 or 1 (Appendix 1)
  • 7. 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
  • 8. 18 years or over
  • 9. Written (signed and dated) informed consent and be capable of co-operating with
  • treatment and follow-up
  • EXCLUSION CRITERIA
  • 1. 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.
  • 2. 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.
  • 3. Known brain metastases.
  • 4. 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.
  • 5. 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).
  • 6. Major thoracic and/or abdominal surgery in the preceding 4 weeks from which the
  • patient has not recovered.
  • 7. At high medical risk because of non-malignant systemic disease including active
  • uncontrolled infection.
  • 8. 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.
  • 9. 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.
  • 10. Any other condition which in the Investigator's opinion would not make the patient a
  • good candidate for the clinical trial.
  • 11. Patients who have already received a PARP inhibitor.
Participant Exclusion Criteria
  • INCLUSION CRITERIA
  • 1. 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.
  • 2. 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.
  • 3. Patients with breast cancer who have had no more than 5 prior chemotherapy regimens
  • in the last 5 years.
  • 4. 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.
  • 5. Life expectancy of at least 12 weeks
  • 6. World Health Organisation (WHO) performance status of 0 or 1 (Appendix 1)
  • 7. 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
  • 8. 18 years or over
  • 9. Written (signed and dated) informed consent and be capable of co-operating with
  • treatment and follow-up
  • EXCLUSION CRITERIA
  • 1. 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.
  • 2. 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.
  • 3. Known brain metastases.
  • 4. 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.
  • 5. 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).
  • 6. Major thoracic and/or abdominal surgery in the preceding 4 weeks from which the
  • patient has not recovered.
  • 7. At high medical risk because of non-malignant systemic disease including active
  • uncontrolled infection.
  • 8. 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.
  • 9. 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.
  • 10. Any other condition which in the Investigator's opinion would not make the patient a
  • good candidate for the clinical trial.
  • 11. Patients who have already received a PARP inhibitor.
Interventions
Drug; rucaparib (CO-338; formally AG-014699 or PF-01367338); null; []; Genetic; protein expression analysis; null; []; Genetic; western blotting; null; []; Other; immunohistochemistry staining method; null; []; Other; liquid chromatography; null; []; Other; mass spectrometry; null; []; Other; pharmacological study; null; []
Design Details
Sorry, this information is not available
Study Design
Masking: Open Label, Primary Purpose: Treatment
Results Reporting
Sorry, this information is not available
Acronym
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Scientific 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
Secondary Trial Identifying Number
CRUK-PH2-052; CRUK-PARP/BRCA; EU-20842; EUDRACT-2006-002348-27
Website
http://www.cancer.gov/clinicaltrials/CRUK-PH2-052
Study Funded By
Cancer Research UK
Funder Type
Sorry, this information is not available
Study Sponsored By
Cancer Research UK
Study Also Sponsored By
Sorry, this information is not available
Primary Sponsor Type
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Secondary Sponsor Type
Sorry, this information is not available
Key Dates

Date of First Enrollment
Date Not Available
Recruitment End Date
Date Not Available
Trial End Date
Date Not Available
Date added to Registry

22 Apr 2008

Last Updated

04 Feb 2015

Date Record Refreshed on UKCTG

31 Jul 2015