6-mercaptopurine (6MP) and low-dose methotrexate in patients with known BRCA defective tumours
| ISRCTN | ISRCTN63150635 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN63150635 |
| EudraCT/CTIS number | 2009-016846-16 |
| ClinicalTrials.gov number | NCT01432145 |
| Secondary identifying numbers | 9671 |
- Submission date
- 06/05/2011
- Registration date
- 06/05/2011
- Last edited
- 23/03/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English Summary
Contact information
Dr Shibani Nicum
Scientific
Scientific
Department of Clinical Oncology
Old Road
Headington
Oxford
OX3 7LJ
United Kingdom
| shibani.nicum@ouh.nhs.uk |
Study information
| Study design | Non-randomised; Interventional; Design type: Screening, Treatment |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | Phase II clinical trial of 6-mercaptopurine (6MP) and low-dose methotrexate in patients with known BRCA defective tumours |
| 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(s) | Oxfordshire REC B, first MREC approval date 24/01/2011, ref: 10/H0605/79 |
| 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 |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | 6-mercaptopurine, methotrexate |
| Primary outcome measure | 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 study start date | 01/04/2011 |
| Overall study end date | 31/12/2014 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Female |
| Target number of participants | Planned Sample Size: 65; UK Sample Size: 65; Description: 65 patients with confirmed BRAC1 or BRAC2 mutant status |
| Total final enrolment | 67 |
| 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 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
- England
- United Kingdom
Study participating centre
Department of Clinical Oncology
Oxford
OX3 7LJ
United Kingdom
OX3 7LJ
United Kingdom
Sponsor information
University of Oxford (UK)
University/education
University/education
Department of Clinical Pharmacology
Radcliffe Infirmary
Woodstock Road
Oxford
OX2 6HE
England
United Kingdom
"ROR" |
https://ror.org/052gg0110 |
|---|
Funders
Funder type
Charity
Cancer Research UK (CRUK) (UK) - Clinical Trials Advisory and Awards Committee (CTAAC)
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan | Not provided at time of registration |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 19/12/2014 | 10/04/2019 | Yes | No |
| Basic results | 20/05/2019 | No | No | ||
| Plain English results | 23/03/2023 | No | Yes | ||
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
23/03/2023: added CRUK link to plain English results.
20/05/2019: The following changes were made to the trial record:
1. Added clinicaltrialsregister.eu link to basic results (scientific).
2. The total final enrollment was added.
10/04/2019: Publication reference added.
15/08/2016: Recruitment end date was changed from 31/12/2014 to 20/10/2014. Study contact email and trial website was updated.
