A Clinical Trial in Patients With BRCA Defective Tumours (6MP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01432145
Recruitment Status : Completed
First Posted : September 12, 2011
Last Update Posted : May 28, 2015
Information provided by (Responsible Party):
University of Oxford

Brief Summary:
This study will evaluate the efficacy and safety of 6MP in combination with methotrexate in patients with breast or ovarian cancer who are known to have a BRCA mutation. 6MP is used instead of 6TG as it is converted to the same cytotoxic moiety as 6TG, ie. thioguanine nucleotides, but with reduced toxic effects. Low dose methotrexate is used in combination with 6MP as it promotes the formation of thioguanine nucleotides.

Condition or disease Intervention/treatment Phase
Breast Cancer Ovarian Cancer Drug: 6-Mercaptopurine Drug: Methotrexate Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 74 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Clinical Trial Of 6-Mercaptopurine (6MP) and Low-Dose Methotrexate In Patients With Known BRCA Defective Tumours
Study Start Date : May 2011
Actual Primary Completion Date : December 2014
Actual Study Completion Date : May 2015

Arm Intervention/treatment
Experimental: 6MP/MTX Drug: 6-Mercaptopurine
The dose of 6MP will be 75mg/m2 body surface area, administered orally (PO) once a day (od) in the morning 1 hour after eating, on a continuous schedule. Tablets should be taken at roughly the same time each day. One cycle is 28 days. Treatment is given continuously (see table below) until disease progression.

Drug: Methotrexate
Methotrexate (20 mg/m2) will be taken orally, once a week, in the morning. One cycle is 28 days. Treatment is given continuously (see table below) until disease progression.

Primary Outcome Measures :
  1. To determine the objective response rate to 6MP/MTX in this patient population. [ Time Frame: Up to 24 weeks after the 30th (65th) patient has been recruited. ]

    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).

    The proportion of patients responding to treatment will be presented, together with 95% confidence intervals, for Stage 1 and overall, if applicable. This will be repeated separately for patients previously treated with/without PARP inhibitors.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. 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 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.
  2. Patients must have measurable disease on computerized tomography (CT) or MRI scan as defined by RECIST criteria.
  3. Age ≥18 years.
  4. ECOG performance score of 0-2.
  5. Life expectancy >12 weeks.
  6. Written informed consent.
  7. Patient willing and able to comply with all protocol requirements.
  8. No prior anti-cancer treatment in previous 4 weeks, other than palliative RT.
  9. Haematological and biochemical indices within the ranges shown below.

    • Lab 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)
    • AST (SGOT) or ALT ≤ 5 x ULN (liver mets)
    • or ≤ 3 x ULN (no liver mets)
    • Alk Phos ≤ 5 x ULN
    • Serum creatinine ≤ 1.5 x ULN
  10. Ascites and pleural effusions must be drained prior to therapy.

Exclusion Criteria:

  1. 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.
  2. Patients found to have a Low/Low genotype on TPMT testing will be excluded.
  3. Pregnant or breast-feeding women or women of childbearing potential unless highly effective methods of contraception are used (see section 7.2.3).
  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 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01432145

United Kingdom
Churchill Hospital
Oxford, United Kingdom, OX3 7LJ
Sponsors and Collaborators
University of Oxford
Principal Investigator: Shibani Nicum University of Oxford

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: University of Oxford Identifier: NCT01432145     History of Changes
Other Study ID Numbers: OCTO_016
First Posted: September 12, 2011    Key Record Dates
Last Update Posted: May 28, 2015
Last Verified: May 2015

Keywords provided by University of Oxford:
BRCA defective

Additional relevant MeSH terms:
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors