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

NCT00664781 | Completed Phase 2

• 5 other identifiers: CDR0000593558CRUK-PH2-052CRUK-PARP/BRCAEU-20842EUDRACT-2006-002348-27
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 7

Brief 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.

Conditions

brca1 Mutation Carrier; brca2 Mutation Carrier; Breast Cancer; Ovarian Cancer

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

Outcome Measures

Primary Outcomes (2)

• 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

Secondary Outcomes (4)

• Time to progression and overall survival

• Plasma levels measured by Liquid Chromatography/Mass Spectrometry/Mass Spectrometry

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

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

Other Outcomes (5)

• TERTIARY OUTCOMES

• TERTIARY OUTCOMES

• TERTIARY OUTCOMES

Interventions

rucaparib (CO-338; formally AG-014699 or PF-01367338) DRUG

protein expression analysis GENETIC

western blotting GENETIC

immunohistochemistry staining method OTHER

liquid chromatography OTHER

mass spectrometry OTHER

pharmacological study OTHER

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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
• years or over
• Written (signed and dated) informed consent and be capable of co-operating with treatment and follow-up

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Cancer Research UK: lead

Study Sites (7)

Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust

Birmingham, England, B15 2TT, United Kingdom

Location

Leeds Cancer Centre at St. James's University Hospital

Leeds, England, LS9 7TF, United Kingdom

Location

Cancer Research UK and University College London Cancer Trials Centre

London, England, W1T 4TJ, United Kingdom

Location

Christie Hospital

Manchester, England, M20 4BX, United Kingdom

Location

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

Newcastle upon Tyne, England, NE4 6BE, United Kingdom

Location

Derriford Hospital

Plymouth, England, PL6 8DH, United Kingdom

Location

Beatson West of Scotland Cancer Centre

Glasgow, Scotland, G12 0YN, United Kingdom

Location

Related Links

• Clinical Trial Results: A Cancer Research UK Phase II Proof of Principle Trial of the activity of the PARP-1 inhibitor, AG-014699

MeSH Terms

Conditions

Breast Neoplasms; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial

Interventions

rucaparib; Blotting, Western; Immunohistochemistry; Chromatography, Liquid; Mass Spectrometry

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Electrophoresis; Chemistry Techniques, Analytical; Investigative Techniques; Electrochemical Techniques; Immunoblotting; Immunoassay; Immunologic Techniques; Molecular Probe Techniques; Histocytochemistry; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Histological Techniques; Chromatography

Study Officials

• Ruth Plummer

  Northern Centre for Cancer Treatment at Newcastle General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2008
• First Posted: April 23, 2008
• Study Start: December 1, 2007
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: May 24, 2016

Record last verified: 2016-05

Locations

GB (7)