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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2012 by University of Oxford
Sponsor:
Information provided by (Responsible Party):
University of Oxford
ClinicalTrials.gov Identifier:
NCT01432145
First received: August 10, 2011
Last updated: July 3, 2012
Last verified: July 2012
  Purpose

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 Intervention Phase
Breast Cancer
Ovarian Cancer
Drug: 6-Mercaptopurine
Drug: Methotrexate
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by University of Oxford:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]

    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.



Estimated Enrollment: 65
Study Start Date: May 2011
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01432145

Locations
United Kingdom
Churchill Hospital Recruiting
Oxford, United Kingdom, OX3 7LJ
Contact: Shibani Nicum       shibani.nicum@orh.nhs.uk   
Principal Investigator: Shibani Nicum         
Sponsors and Collaborators
University of Oxford
Investigators
Principal Investigator: Shibani Nicum University of Oxford
  More Information

No publications provided

Responsible Party: University of Oxford
ClinicalTrials.gov Identifier: NCT01432145     History of Changes
Other Study ID Numbers: OCTO_016
Study First Received: August 10, 2011
Last Updated: July 3, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by University of Oxford:
BRCA defective

Additional relevant MeSH terms:
Breast Neoplasms
Ovarian Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Endocrine Gland Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
6-Mercaptopurine
Methotrexate
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents

ClinicalTrials.gov processed this record on August 20, 2014