A Clinical Trial in Patients With Breast Cancer Susceptibility Gene (BRCA) Defective Tumours

NCT01432145 | Completed Phase 2 Results

• 1 other identifier: OCTO_016
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate the efficacy and safety of 6-mercaptopurine (6MP) in combination with methotrexate (MTX) in patients with breast or ovarian cancer who are known to have a BRCA (breast cancer gene) mutation.

Conditions

Breast Cancer; Ovarian Cancer

Keywords

BRCA defective

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate to 6-mercaptopurine and Methotrexate (6MP/MTX) in This Patient Population.

  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

Secondary Outcomes (1)

• Quality of Life - EuroQol Group, Five Dimensions, Three-level (EQ-5D-3L) Standardized Instrument for Measuring Generic Health Status

  At the end of treatment or 12 months

Study Arms (1)

6MP/MTX

EXPERIMENTAL

6-Mercaptopurine 55mg/m2 per day, and methotrexate 15mg/m2 per week

Drug: 6-Mercaptopurine; Drug: Methotrexate

Interventions

6-Mercaptopurine DRUG

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.

Also known as: 6MP

6MP/MTX

Methotrexate DRUG

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.

Also known as: MTX

6MP/MTX

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Oxford: lead

Study Sites (1)

Churchill Hospital

Oxford, OX3 7LJ, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 31813938 DERIVED

• 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.

  PMID: 25526776 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Ovarian Neoplasms

Interventions

Mercaptopurine; Methotrexate

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Sulfhydryl Compounds; Sulfur Compounds; Organic Chemicals; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Aminopterin; Pterins; Pteridines

Limitations and Caveats

Quality of life, a secondary endpoint, could not be analysed due to the low questionnaire completion rate.

Results Point of Contact

• Title: Ms Heather House
• Organization: University of Oxford Clinical Trials & Research Governance

heather.house@admin.ox.ac.uk

01865 572245

Study Officials

• Shibani Nicum

  University of Oxford

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 10, 2011
• First Posted: September 12, 2011
• Study Start: May 1, 2011
• Primary Completion: December 1, 2014
• Study Completion: May 1, 2015
• Last Updated: July 9, 2019
• Results First Posted: May 17, 2019

Record last verified: 2018-06

Locations

GB (1)