A Phase II Clinical Trial in Patients with BRCA defective Tumours

Phase 1

• Conditions: Advanced or metastatic breast or ovarian cancer.; MedDRA version: 16.1 Level: LLT Classification code 10028985 Term: Neoplasm breast System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 16.1 Level: PT Classification code 10033128 Term: Ovarian cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

• Registration Number: EUCTR2009-016846-16-GB
• Lead Sponsor: niversity of Oxford

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2010-11-25
• Study Completion: 2017-02-16
• Last Update Posted: 30 April 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 67

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 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.
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 patient 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.

OR

Ovarian/ Fallopian tube/ Primary Serous Peritoneal Cancer
a) Patients with initially histologically or cytologically proven ovarian, fallopian tube 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
8.No prior anti-cancer treatment in previous 4 weeks, other than palliative RT.
9. Haematological and biochemical indices within the ranges given at screening and on cycle 1 day 1.
10. Ascites and pleural effusions must be drained prior to therapy
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 0
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 0

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 on TPMT testing will be excluded.
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 are excluded.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified