Title

6MP

Chief Investigator: 
Shibani Nicum

Sponsor: University of Oxford
EudraCT number: 2009-016846-16

To determine the response rates and toxicity of 6MP with low dose methotrexate in patients with breast, ovarian, fallopian tube or primary serous peritoneal cancer who are known to have a BRCA mutation.

A Phase II Clinical trial in patients with known BRCA Defective Tumours.

6MP is closed to recruitment and is in follow-up.

Study Status

CLOSED to recruitment

Target recuitment:

71 (65 evaluable)

Final recruitment:

74 patients (Evaluable TBC)

Participant sites:

14

  • Belfast City Hospital, Belfast
  • Christie Hospital, Manchester
  • Churchill Hospital, Oxford
  • Clatterbridge, Wirral
  • Freeman Hospital, Manchester
  • Guy's Hospital, London
  • Mount Vernon Hospital, Middlesex
  • Royal Marsden Hospital, Sutton
  • Royal Marsden Hospital, London
  • Royal United Hospital, Bath
  • University College London Hospital
  • University Hospital Coventry
  • Velindre Hospital, Cardiff
  • Western General Hospital, Edinburgh

Click here for 6MP Sites Location Map

Inclusion Criteria

  1. Patients with proven BRCA1 or BRCA2 mutations and after appropriate  exposure to standard treatment, as defined by:

Breast Cancer

  • Patients with initially histologically or cytologicallyproven 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 (by expected toxicities or patient refusal)
  • Patients with hormone responsive disease should have had at least 1 line of hormone therapy for metastatic disease unless contraindicated (by expected toxicities or patient refusal).
  • Prior treatment with a PARP inhibitor is permissible.
OR 
 
Ovarian/ Fallopian tube/ Primary Serous Peritoneal  Cancer
  • Patients with initially histologically or cytologically proven ovarian cancer, fallopian tube cancer or primary serous peritoneal 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.
  1. Patients must have measurable disease as defined by RECIST v1.1 criteria
  2. Age ≥18 years
  3. ECOG performance score of 0-2
  4. Life expectancy of >12 weeks
  5. Adequate haematological and biochemical function
  6. Written informed consent

Exclusion Criteria

  1. Patients with any of the following contra-indications to thiopurines (6MP/6TG) or methotrexate:
  • family history of severe liver failure;
  • porphyria;
  • diffuse infiltrative pulmonary or pericardial disease;
  • known hypersensitivity to either trial agent.Patients found to have a Low/Low genotype on TPMT testing.
  1. Pregnant or breast-feeding women.
  2. Any other active malignancy requiring treatment/or whose prognosis will prevent readout from trial endpoints.
  3. Patients known or tested to be serologically positive for Hepatitis B, Hepatitis C or HIV.
  4. 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.
  5. Patients who have received anticancer agent(s) or an investigational agent within 28 days prior to study drug administration.
  6. 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.

Objectives

Primary:

  • To determine the objective response rate to 6MP/MTX in this patient population.

Secondary:

  • To evaluate overall survival after treatment with 6MP/MTX.
  • To evaluate progression free survival (PFS) after treatment with 6MP/MTX.
  • Safety of 6MP/MTX.
  • To study pharmacokinetics of 6MP/MTX in these patient populations.
  • To study the effect of patient pharmacogenomics on thiopurine metabolism.
  • Assessment of feasibility as a multi-centre study.
  • Assessment of quality of life.

Exploratory:

  • To evaluate Mismatch repair (MMR) status of  patients at initial diagnosis, prior to starting study and after 7 weeks of treatment.

Data Submission

Data submission for this trial is via electronic submission of data in OpenClinica. 

OpenClinica Training

OpenClinica is the world's leading open source clinical trial software for electronic data capture and clinical data management. 

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