- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01432145
A Clinical Trial in Patients With Breast Cancer Susceptibility Gene (BRCA) Defective Tumours (6MP)
Phase II Clinical Trial Of 6-Mercaptopurine (6MP) and Low-Dose Methotrexate In Patients With Known BRCA Defective Tumours
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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-
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Oxford, United Kingdom, OX3 7LJ
- Churchill Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
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 Criteria:
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: 6MP/MTX
6-Mercaptopurine 55mg/m2 per day, and methotrexate 15mg/m2 per week
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6-Mercaptopurine (6MP) 55mg/m2 body surface area, administered orally (PO) once a day (od) in the morning 1 hour after eating, on a continuous schedule.
One cycle is 28 days.
Treatment is given continuously until disease progression.
Other Names:
Methotrexate (MTX) 15 mg/m2 taken orally, once a week, in the morning.
One cycle is 28 days.
Treatment is given continuously until disease progression.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective Response Rate to 6-mercaptopurine and Methotrexate (6MP/MTX) in This Patient Population.
Time Frame: 8 weeks after start of treatment
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1st stage: If less than 3/30 evaluable patients respond at 8 weeks the trial will be stopped for futility. If 3 or more out of 30 evaluable patients respond then a further 35 patients will be recruited (2nd stage) - this was met. The proportion of patients responding to treatment (complete response, partial response or stable disease) at the second stage will be presented per Response Evaluation Criteria In Solid Tumours (RECIST) criteria version 1.1 measured radiologically with computerised tomography (CT) and/or magnetic resonance imaging (MRI); the same method is used at baseline and at follow-up: Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Patients who yield progressive disease (PD) are classed as non-responders. |
8 weeks after start of treatment
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Quality of Life - EuroQol Group, Five Dimensions, Three-level (EQ-5D-3L) Standardized Instrument for Measuring Generic Health Status
Time Frame: At the end of treatment or 12 months
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Evaluated using the EQ-5D-3L questionnaire at baseline, 3 and 6 months, and at the end of treatment or 12 months, as well as using the ECOG performance status measure after each cycle
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At the end of treatment or 12 months
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Shibani Nicum, University of Oxford
Publications and helpful links
General Publications
- Roberts C, Strauss VY, Kopijasz S, Gourley C, Hall M, Montes A, Abraham J, Clamp A, Kennedy R, Banerjee S, Folkes LK, Stratford M, Nicum S. Results of a phase II clinical trial of 6-mercaptopurine (6MP) and methotrexate in patients with BRCA-defective tumours. Br J Cancer. 2020 Feb;122(4):483-490. doi: 10.1038/s41416-019-0674-4. Epub 2019 Dec 9.
- Nicum S, Roberts C, Boyle L, Kopijasz S, Gourley C, Hall M, Montes A, Poole C, Collins L, Schuh A, Dutton SJ; 6MP Collaborative Group. A phase II clinical trial of 6-mercaptopurine (6MP) and methotrexate in patients with BRCA defective tumours: a study protocol. BMC Cancer. 2014 Dec 19;14:983. doi: 10.1186/1471-2407-14-983.
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Skin Diseases
- Neoplasms
- Neoplasms by Site
- Breast Diseases
- Breast Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Dermatologic Agents
- Reproductive Control Agents
- Abortifacient Agents, Nonsteroidal
- Abortifacient Agents
- Folic Acid Antagonists
- Methotrexate
- Mercaptopurine
Other Study ID Numbers
- OCTO_016
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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