Breast CancerPhase 26MPNCT01432145
A Clinical Trial in Patients With Breast Cancer Susceptibility Gene (BRCA) Defective Tumours
A Phase 2 study testing 6-Mercaptopurine and Methotrexate in people with Breast Cancer and Ovarian Cancer, run by University of Oxford at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer, Ovarian Cancer
- What is being tested?
- 6-Mercaptopurine and Methotrexate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 74 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- May 2011to May 2015
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 29Show fewer
- 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.
- Patient willing and able to comply with all protocol requirements.
- No prior anti-cancer treatment in previous 4 weeks, other than palliative radiotherapy (RT).
- Haematological and biochemical indices within the ranges shown below.
- Laboratory 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)
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase (SGOT)) and alanine aminotransferase (ALT) or ALT ≤ 5 x ULN (liver metastasis)
- or ≤ 3 x ULN (no liver metastasis)
- Alkaline phosphatase ≤ 5 x ULN
- Serum creatinine ≤ 1.5 x ULN
- Ascites and pleural effusions must be drained prior to therapy.
Who cannot join
- 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.
Show all 13Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase II Clinical Trial Of 6-Mercaptopurine (6MP) and Low-Dose Methotrexate In Patients With Known BRCA Defective Tumours
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.
Read the detailed description
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. 6MP is used instead of 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.
- Conditions
- Breast Cancer, Ovarian Cancer
- Being tested
- 6-Mercaptopurine, Methotrexate
- Keywords
- BRCA defective
- Medical subject headings
- Breast Neoplasms, Ovarian Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
6-MercaptopurineDrug
Also called 6MP
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.
MethotrexateDrug
Also called MTX
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.
| Study group | Role | What they receive |
|---|---|---|
| 6MP/MTX | Experimental | 6-Mercaptopurine 55mg/m2 per day, and methotrexate 15mg/m2 per week Receives: Drug: 6-Mercaptopurine; Drug: Methotrexate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Evaluated using the EQ-5D-3L questionnaire at baseline, 3 and 6 months, and at the end of treatment or 12 months, as well as using the ECOG performance status measure after each cycle
Measured: At the end of treatment or 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Sep 2011 (estimated)
- Study startMay 2011
- Primary completionDec 2014
- Study completionMay 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 74 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Shibani Nicum, Principal investigator, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01432145
- Sponsor's protocol ID
- OCTO_016
- Acronym
- 6MP
- Status last verified
- Jun 2018
- First submitted
- 10 Aug 2011
- Last updated
- 9 Jul 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 31813938Nicum 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.
PubMed 25526776