6-mercaptopurine (6MP) and low-dose methotrexate in patients with known BRCA defective tumours
- Conditions
- Breast cancer, ovarian cancerTopic: National Cancer Research NetworkSubtopic: Breast Cancer, Gynaecological CancerDisease: Breast, OvaryCancer
- Registration Number
- ISRCTN63150635
- Lead Sponsor
- niversity of Oxford (UK)
- Brief Summary
2014 Protocol article in https://www.ncbi.nlm.nih.gov/pubmed/25526776 protocol (added 10/04/2019)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Female
- Target Recruitment
- 67
Patients with proven BRCA1 or BRCA2 mutations and after appropriate exposure to standard treatment, as defined by:
1. Breast cancer
1.1. 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
1.2. Patients must have previously had a taxane and an anthracycline in either the adjuvant or metastatic setting, provided that these were not contraindicated
1.3. Patients with hormone responsive disease should have had at least one line of hormone therapy for metastatic disease
1.4. Prior treatment with a Poly (ADP-ribose) polymerase (PARP) inhibitor is permissible
2. Ovarian cancer
2.1. Patients with initially histologically or cytologically proven ovarian cancer
2.2. Patients must have disease that is platinum resistant or in whom further platinum based therapy is inappropriate
2.3. Prior treatment with a PARP inhibitor is permissible
3. Patients must have measurable disease on computerised tomography (CT) or magnetic resonance imaging (MRI) scan as defined by Response Evaluation Criteria In Solid Tumors (RECIST) criteria
4. Age more than or equal to 18 years
5. ECOG performance score of 0-2
6. Life expectancy of > 12 weeks
7. Adequate haematological and biochemical function
8. Written informed consent; Target Gender: Female ; Lower Age Limit 18 years
1. Patients with any of the following contra-indications to thiopurines (6MP/6TG) or methotrexate:
1.1. Family history of severe liver failure
1.2. Porphyria
1.3. Diffuse infiltrative pulmonary or pericardial disease
1.4. Known hypersensitivity to either trial agent
2. Patients found to have a Low/Low genotype on Thiopurine S-methyl transferase (TPMT) testing
3. Pregnant or breast-feeding women
4. 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
5. Patients known or tested to be serologically positive for hepatitis B, hepatitis C or human immunodeficiency virus (HIV)
6. Patients with active 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.
7. Patients who have received anticancer agent(s) or an investigational agent within 28 days prior to study drug administration
8. 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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Objective tumour response rate (radiological) at 8 weeks.; Timepoint(s): 8 weeks
- Secondary Outcome Measures
Name Time Method <br> 1. Assessment of feasibility as a multi-centre study; Timepoint(s): End of study<br> 2. Assessment of quality of life.; Timepoint(s): Baseline,3 months, 6 months, end of treatment or 12 months<br> 3. Assessment of the safety and toxicity of 6MP and low dose methotrexate; Timepoint(s): Duration of study<br> 4. Biochemical response rates (ovarian cancer patients only); Timepoint(s): Duration of the study<br> 5. Overall survival at 1 and 2 years post entry into the study; Timepoint(s): Up to 2 years post study entry<br> 6. Progression free survival.; Timepoint(s): Duration of study<br>