Advanced or metastatic breast or ovarian cancer. MedDRA version: 16.1 Level: LLT Classification code 10028985 Term: Neoplasm breast System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 16.1 Level: PT Classification code 10033128 Term: Ovarian cancer System Organ Class: 10029
Conditions
Interventions
Trade Name: Puri-Nethol
Product Name: 6 Mercaptopurine
Pharmaceutical Form: Tablet
INN or Proposed INN: 6 Mercaptopurine
CAS Number: 50-
Sponsors
University of Oxford
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Patients with proven BRCA1 or BRCA2 mutations and after appropriate exposure to standard treatment, as defined by: Breast Cancer a) 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. b) Patients must have previously had a taxane and an anthracycline in either the adjuvant or metastatic setting, provided that these were not contraindicated(by patient toxicities or patient refusal). c) Patients with hormone responsive disease should have had at least 1 line of hormone therapy for metastatic disease unless contraindicated (by expected toxicities or patient refusal). d) Prior treatment with a PARP inhibitor is permissible. OR Ovarian/ Fallopian tube/ Primary Serous Peritoneal Cancer a) Patients with initially histologically or cytologically proven ovarian, fallopian tube or primary serous peritoneal cancer. b) Patients must have disease that is platinum resistant or in whom further platinum based therapy is inappropriate. c) Prior treatment with a PARP inhibitor is permissible. 2. Patients must have measurable disease as defined by RECIST v1.1 criteria; 3. Age =18 years 4. ECOG performance score of 0-2 5. Life expectancy of >12 weeks 6. Adequate haematological and biochemical function. 7. Written informed consent 8. No prior anti-cancer treatment in previous 4 weeks, other than palliative RT. 9. Haematological and biochemical indices within the ranges given at screening and on cycle 1 day 1. 10. Ascites and pleural effusions must be drained prior to therapy Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 0 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: 1. Patients with any of the following contra-indications to thiopurines (6MP/ 6TG) or methotrexate: • family history of severe liver failure; • porphyria; • diffuse infiltrative pulmonary or pericardial disease; • known hypersensitivity to either trial agent. 2. Patients found to have a Low/Low genotype on TPMT testing will be excluded. 3. Pregnant or breast-feeding women 4. Any other active malignancy requiring treatment/ or whose prognosis will prevent readout from trial endpoints. 5. Patients known or tested to be serologically positive for Hepatitis B, Hepatitis C or 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 are excluded.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): To determine the objective response rate at 8 weeks to 6MP/methotrexate in this patient population. ;Timepoint(s) of evaluation of this end point: Disease response at 8 weeks using RECIST v1.1.; Main Objective: To determine the anti-cancer activity of 6MP with low dose Methotrexate in patients with breast, ovarian, fallopian tube or primary serous peritoneal cancer and a known BRCA mutation. ; Secondary Objective: The secondary objectives of this study are to assess: - progression of the disease(progression free survival) - Overall survival (survival at 1-2 years) - safety and tolerability of 6MP with Methotrexate. - the biochemical response rates for ovarian, fallopian tube or primary serous peritoneal cancer based on changes in the serum levels of CA125, a cancer antigen. - Assessment of the TPMT genotype using a validated assay. - quality of life (QOL) of the patients enrolled. In addition, this study will look at the rates of recruitment to determine the feasibility of performing studies in small patient subgroups with BRCA mutated cancer. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To evaluate overall survival after treatment with 6MP/methotrexate. To evaluate progression free survival (PFS) after treatment with 6MP/methotrexate. Safety of 6MP/methotrexate. To study the effect of patient pharmacogenomics on thiopurine metabolism. Assessment of feasibility as a multi-centre study. Assessment of quality of life. ;Timepoint(s) of evaluation of this end point: Overall survival after treatment with 6MP/methotrexate, including at 1 and 2 years. | — |
Countries
United Kingdom
Outcome results
None listed