Condition category
Cancer
Date applied
06/05/2011
Date assigned
06/05/2011
Last edited
15/08/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Contact information

Type

Scientific

Primary contact

Dr Shibani Nicum

ORCID ID

Contact details

Department of Clinical Oncology
Old Road
Headington
Oxford
OX3 7LJ
United Kingdom
-
shibani.nicum@ouh.nhs.uk

Additional identifiers

EudraCT number

2009-016846-16

ClinicalTrials.gov number

NCT01432145

Protocol/serial number

9671

Study information

Scientific title

Phase II clinical trial of 6-mercaptopurine (6MP) and low-dose methotrexate in patients with known BRCA defective tumours

Acronym

Study hypothesis

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 6- Thioguanine (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.

On 06/11/2014 the anticipated end date was changed from 30/09/2015 to 31/12/2014.

Ethics approval

Oxfordshire REC B, first MREC approval date 24/01/2011, ref: 10/H0605/79

Study design

Non-randomised; Interventional; Design type: Screening, Treatment

Primary study design

Interventional

Secondary study design

Non randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details to request a patient information sheet

Condition

Topic: National Cancer Research Network; Subtopic: Breast Cancer, Gynaecological Cancer; Disease: Breast, Ovary

Intervention

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; methotrexate (20 mg/m2) will be taken orally, once a week, in the morning.; Follow Up Length: 24 month(s); Study Entry : Registration only

Intervention type

Drug

Phase

Phase II

Drug names

6-mercaptopurine, methotrexate

Primary outcome measures

Objective tumour response rate (radiological) at 8 weeks.; Timepoint(s): 8 weeks

Secondary outcome measures

1. Assessment of feasibility as a multi-centre study; Timepoint(s): End of study
2. Assessment of quality of life.; Timepoint(s): Baseline,3 months, 6 months, end of treatment or 12 months
3. Assessment of the safety and toxicity of 6MP and low dose methotrexate; Timepoint(s): Duration of study
4. Biochemical response rates (ovarian cancer patients only); Timepoint(s): Duration of the study
5. Overall survival at 1 and 2 years post entry into the study; Timepoint(s): Up to 2 years post study entry
6. Progression free survival.; Timepoint(s): Duration of study

Overall trial start date

01/04/2011

Overall trial end date

31/12/2014

Reason abandoned

Eligibility

Participant inclusion criteria

Patients with proven BRCA1 or BRCA2 mutations and after appropriate exposure to standard treatment, as defined by:
1. Breast cancer
1.1. 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
1.2. Patients must have previously had a taxane and an anthracycline in either the adjuvant or metastatic setting, provided that these were not contraindicated
1.3. Patients with hormone responsive disease should have had at least one line of hormone therapy for metastatic disease
1.4. Prior treatment with a Poly (ADP-ribose) polymerase (PARP) inhibitor is permissible
2. Ovarian cancer
2.1. Patients with initially histologically or cytologically proven ovarian cancer
2.2. Patients must have disease that is platinum resistant or in whom further platinum based therapy is inappropriate
2.3. Prior treatment with a PARP inhibitor is permissible
3. Patients must have measurable disease on computerised tomography (CT) or magnetic resonance imaging (MRI) scan as defined by Response Evaluation Criteria In Solid Tumors (RECIST) criteria
4. Age more than or equal to 18 years
5. ECOG performance score of 0-2
6. Life expectancy of > 12 weeks
7. Adequate haematological and biochemical function
8. Written informed consent; Target Gender: Female ; Lower Age Limit 18 years

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

Planned Sample Size: 65; UK Sample Size: 65; Description: 65 patients with confirmed BRAC1 or BRAC2 mutant status

Participant exclusion criteria

1. Patients with any of the following contra-indications to thiopurines (6MP/6TG) or methotrexate:
1.1. Family history of severe liver failure
1.2. Porphyria
1.3. Diffuse infiltrative pulmonary or pericardial disease
1.4. Known hypersensitivity to either trial agent
2. Patients found to have a Low/Low genotype on Thiopurine S-methyl transferase (TPMT) testing
3. Pregnant or breast-feeding women
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 human immunodeficiency virus (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

Recruitment start date

01/04/2011

Recruitment end date

20/10/2014

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Department of Clinical Oncology
Oxford
OX3 7LJ
United Kingdom

Sponsor information

Organisation

University of Oxford (UK)

Sponsor details

Department of Clinical Pharmacology
Radcliffe Infirmary
Woodstock Road
Oxford
OX2 6HE
United Kingdom

Sponsor type

University/education

Website

Funders

Funder type

Charity

Funder name

Cancer Research UK (CRUK) (UK) - Clinical Trials Advisory and Awards Committee (CTAAC)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

15/08/2016: Recruitment end date was changed from 31/12/2014 to 20/10/2014. Study contact email and trial website was updated.