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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.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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
Are there results?
Yes, posted in the registrySummary in the doctors' view

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.
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  • 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.
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  • 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.

United Kingdom1 site

  • Churchill Hospital

    Oxford, OX3 7LJ

Other trials in United Kingdom

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.

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 groups in NCT01432145
Study groupRoleWhat they receive
6MP/MTXExperimental6-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.

  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.

    Measured: 8 weeks after start of treatment

Secondary outcomes (1)

  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.

  1. First posted12 Sep 2011 (estimated)
  2. Study startMay 2011
  3. Primary completionDec 2014
  4. Study completionMay 2015

Resources

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)
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
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 31813938

  • 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.

    PubMed 25526776

Questions about this trial

What is this clinical trial studying?

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.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 29 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate to 6-mercaptopurine and Methotrexate (6MP/MTX) in This Patient Population. (time frame: 8 weeks after start of treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01432145, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jul 2019; AzTrials last refreshed its copy on 26 Oct 2026.

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