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Health Condition(s) or Problem
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brca1 Mutation Carrier; brca2 Mutation Carrier; Breast Cancer; Ovarian Cancer
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Lay Summary
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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.
(from ClinicalTrials.gov)
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Who can enter the trial
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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
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Who cannot enter the trial
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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
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What will happen
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Drug; rucaparib (CO-338; formally AG-014699 or PF-01367338); Genetic; protein expression analysis; Genetic; western blotting; Other; immunohistochemistry staining method; Other; liquid chromatography; Other; mass spectrometry; Other; pharmacological study
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Primary aim
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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; Safety profile
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Secondary Aim
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Time to progression and overall survival; No; Plasma levels measured by Liquid Chromatography/Mass Spectrometry/Mass Spectrometry; No; Poly(ADP-ribose) polymerase (PARP) activity measured ex vivo using validated assays; No; To determine the optimal oral dosing regimen, based on the assessment of antitumor activity and the safety profile; Yes
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Participant Information Sheet
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Sorry, not currently available
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Website
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http://www.cancer.gov/clinicaltrials/CRUK-PH2-052
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Recruitment Status
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Recruiting
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Nation
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England, Scotland
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Location
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Birmingham, Leeds, London, Manchester, Newcastle upon Tyne, Plymouth, Glasgow
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