6MP

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

6MP is actively recruiting

EudraCT number: 2009-016846-16
Chief Investigator: Dr Shibani Nicum
Sponsor: University of Oxford

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.

STUDY STATUS

Open to recruitment.
Target recruitment: 65
Current recruitment: 20 patients (March 2012)
Active sites: 10 (March 2012)

INCLUSION CRITERIA

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

Breast Cancer
a) 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.
b) 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)
c) 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).
d) Prior treatment with a PARP inhibitor is permissible.

Ovarian/ Fallopian tube/ Primary Serous Peritoneal Cancer

a) Patients with initially histologically or cytologically proven ovarian cancer, fallopian tube cancer or primary serous peritoneal cancer.

b) Patients must have disease that is platinum resistant or in whom further platinum based therapy is inappropriate.

c) Prior treatment with a PARP inhibitor is permissible.

2. Patients must have measurable disease as defined by RECIST v1.1 criteria

3. Age ≥18 years

4. ECOG performance score of 0-2

5. Life expectancy of >12 weeks

6. Adequate haematological and biochemical function

7. 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.

2. Patients found to have a Low/Low genotype and / or a low activity (20 – 67 mU/L) on TPMT testing.

3. Pregnant or breast-feeding women

4. Any other active malignancy requiring treatment/ or whose prognosis will prevent readout from trial endpoints.

5. Patients known or tested to be serologically positive for Hepatitis B, Hepatitis C or 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.

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.

OpenClinica

Data submission for this trial is via electronic submission of data in OpenClinica. OpenClinica is the world's leading open source clinical trial software for electronic data capture and clinical data management. Information on how to use OpenClinica can be found on the OpenClinica Training page using the link below. It contains a user guide and instructional videos to show you how to use OpenClinica. After reviewing these if you have any other queries please contact a member of the trial team at OCTO.

» OpenClinica Training

Oncology Clinical Trials Office (OCTO)

Randomisation Service Mon-Fri 9-5 (UK Time):

Tel: 0800 389 1635, Fax: 0800 389 1629 (24hrs)

Trial Team: Tel: +44 (0)1865 617 011, Fax: +44 (0)1865 617 010 (24hrs)

General OCTO Enquiries: Tel: +44 (0)1865 617 000, Fax: +44 (0)1865 617 010

Email: 6MP@octo-oxford.org.uk

Website: www.octo-oxford.org.uk