Status:
COMPLETED
A Clinical Trial in Patients With Breast Cancer Susceptibility Gene (BRCA) Defective Tumours
Lead Sponsor:
University of Oxford
Conditions:
Breast Cancer
Ovarian Cancer
Eligibility:
FEMALE
18+ years
Phase:
PHASE2
Brief Summary
This study will evaluate the efficacy and safety of 6-mercaptopurine (6MP) in combination with methotrexate (MTX) in patients with breast or ovarian cancer who are known to have a BRCA (breast cancer ...
Detailed Description
This study will evaluate the efficacy and safety of 6-mercaptopurine (6MP) in combination with methotrexate (MTX) in patients with breast or ovarian cancer who are known to have a BRCA (breast cancer ...
Eligibility Criteria
Inclusion
- Patients with proven BRCA1 or BRCA2 mutations and after appropriate exposure to standard treatment, as defined by:
- Breast Cancer
- Patients with initially histologically or cytologically proven locally advanced or metastatic breast cancer who may have received up to 3 previous lines of chemotherapy in the locally advanced or metastatic breast cancer setting.
- Patients must have previously had a taxane and an anthracycline in either the adjuvant or metastatic setting, provided that these were not contraindicated.
- Patients with hormone responsive disease should have had at least 1 line of hormone therapy for metastatic disease.
- Prior treatment with a poly-Adenosine diphosphate (ADP) ribose polymerase (PARP) inhibitor is permissible.
- OR Ovarian Cancer
- Patients with initially histologically or cytologically proven ovarian cancer.
- Patients must have disease that is platinum resistant or in whom further platinum based therapy is inappropriate.
- Prior treatment with a PARP inhibitor is permissible.
- Patients must have measurable disease on computerized tomography (CT) or Magnetic resonance imaging (MRI) scan as defined by Response Evaluation Criteria In Solid Tumors (RECIST) criteria.
- Age ≥18 years.
- Eastern Cooperative Oncology Group (ECOG) performance score of 0-2.
- Life expectancy \>12 weeks.
- Written informed consent.
- Patient willing and able to comply with all protocol requirements.
- No prior anti-cancer treatment in previous 4 weeks, other than palliative radiotherapy (RT).
- Haematological and biochemical indices within the ranges shown below.
- Laboratory Test Value required
- Haemoglobin (Hb) \> 10g/dL
- White Blood Count (WBC) \> 3x109/L
- Platelet count \> 100,000/μL
- Absolute Neutrophil count \> 1.5x109/L;
- Serum bilirubin ≤ 2 x Upper limit normal (ULN)
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase (SGOT)) and alanine aminotransferase (ALT) or ALT ≤ 5 x ULN (liver metastasis)
- or ≤ 3 x ULN (no liver metastasis)
- Alkaline phosphatase ≤ 5 x ULN
- Serum creatinine ≤ 1.5 x ULN
- Ascites and pleural effusions must be drained prior to therapy.
Exclusion
- Patients with any of the following contra-indications to thiopurines (6MP or 6TG) or methotrexate:
- family history of severe liver failure;
- alcoholism;
- porphyria;
- diffuse infiltrative pulmonary or pericardial disease;
- known hypersensitivity to either trial agent.
- Patients found to have a Low/Low genotype on thiopurine methyltransferase (TPMT) testing will be excluded.
- Pregnant or breast-feeding women or women of childbearing potential unless highly effective methods of contraception are used.
- Other active malignancy, with the exception of adequately treated in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin.
- Patients known or tested to be serologically positive for Hepatitis B, Hepatitis C or human immunodeficiency virus (HIV).
- Patients with active central nervous system (CNS) lesions are excluded (i.e., those with radiographically unstable, symptomatic lesions). However, patients treated with stereotactic therapy or surgery and/or whole brain radiotherapy are eligible if the patient remains without evidence of disease progression in brain ≥ 3 months prior to registration date . They must also be off corticosteroid therapy for ≥ 3 weeks prior to registration date.
- Patients who have received anticancer agent(s) or an investigational agent within 28 days prior to study drug administration.
- Subjects who have not recovered to within one grade level (not to exceed grade 2) of their baseline following a significant adverse event or toxicity attributed to previous anticancer treatment are excluded.
Key Trial Info
Start Date :
May 1 2011
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
May 1 2015
Estimated Enrollment :
74 Patients enrolled
Trial Details
Trial ID
NCT01432145
Start Date
May 1 2011
End Date
May 1 2015
Last Update
July 9 2019
Active Locations (1)
Enter a location and click search to find clinical trials sorted by distance.
1
Churchill Hospital
Oxford, United Kingdom, OX3 7LJ