Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Symptoms and General Pathology

Rare Diseases

Breast Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Disease Susceptibility

Breast Diseases

Skin Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Antineoplastic Agents

Antirheumatic Agents

Dermatologic Agents

Reproductive Control Agents

All Drugs and Chemicals

Micronutrients

Hematinics

Vitamins

Methotrexate

Mercaptopurine

Antimetabolites

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Immunosuppressive Agents

Immunologic Factors

Folinic Acid

Folate

Vitamin B9

6-Mercaptopurine 55mg/m2 per day, and methotrexate 15mg/m2 per week

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.

6-Mercaptopurine

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.

Shibani Nicum

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.

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.

A Clinical Trial in Patients With Breast Cancer Susceptibility Gene (BRCA) Defective Tumours

Phase II Clinical Trial Of 6-Mercaptopurine (6MP) and Low-Dose Methotrexate In Patients With Known BRCA Defective Tumours

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.

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

University of Oxford

For Adverse Events (AEs), Grade 3 and 4 AEs and Grade 2 Adverse Drug Reactions (ADRs) were collected.

6-Mercaptopurine: The dose of 6MP will be 75mg/m2 body surface area, administered orally (PO) once a day (od) in the morning 1 hour after eating, on a continuous schedule. Tablets should be taken at roughly the same time each day. One cycle is 28 days. Treatment is given continuously (see table below) until disease progression.

Methotrexate: Methotrexate (20 mg/m2) will be taken orally, once a week, in the morning. One cycle is 28 days. Treatment is given continuously (see table below) until disease progression.

6MP/MTX

6-Mercaptopurine: The dose of 6MP will be 75mg/m2 body surface area, administered orally (PO) once a day (od) in the morning 1 hour after eating, on a continuous schedule. Tablets should be taken at roughly the same time each day. One cycle is 28 days. Treatment is given continuously until disease progression.

Methotrexate: Methotrexate (20 mg/m2) will be taken orally, once a week, in the morning. One cycle is 28 days. Treatment is given continuously until disease progression.

Update: These original doses were reduced following an Urgent Safety Measure in August 2012 due to a large proportion of patients requiring a dose reduction or treatment delay due to incidences of myelo-suppression.

The reduced doses were 55mg/m2 of 6MP orally once a day, and 15mg/m2 of Methotrexate orally once a week.

Age, Continuous

Age categorical

Age, Customized

Sex: Female, Male

Race and Ethnicity were not collected from any participant.

Race and Ethnicity Not Collected

United Kingdom

Region of Enrollment

Breast Cancer gene (BRCA) Status

Prior poly-Adenosine diphosphate (ADP) ribose polymerase (PARP) treatment

ECOG performance status is a scale used to assess how a patient's disease is progressing, assess how the disease affects the daily living abilities of the patient, and determine appropriate treatment and prognosis.

Grade 0: fully active. Grade 1: restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature Grade 2: up and about more than 50% of waking hours Grade 3: confined to bed or chair more than 50% of waking hours Grade 4: completely disabled Grade 5: dead

Eastern Cooperative Oncology Group (ECOG) Performance Status

Albumin levels

Thiopurine methyltransferase (TPMT)

Quality of life, a secondary endpoint, could not be analysed due to the low questionnaire completion rate.

Ms Heather House

6-Mercaptopurine: 6MP 75mg/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.

Methotrexate: Methotrexate 20mg/m2 will be taken orally, once a week, in the morning. One cycle is 28 days. Treatment is given continuously until disease progression.

Update: These original doses were reduced following an Urgent Safety Measure in August 2012 due to a large proportion of patients requiring a dose reduction or treatment delay due to incidences of myelo-suppression.

The reduced doses were 55mg/m2 of 6MP orally once a day, and 15mg/m2 of Methotrexate orally once a week.

6-Mercaptopurine and Methotrexate (6MP/MTX)

Evaluable patients are those patients who complete at least 4 out of 8 weeks of trial medication and are assessed for response as per RECIST v1.1 at 8 weeks. Patient who stop trial medication early due to disease progression are also fully evaluable as they have reached an end point.

Objective Response Rate to 6-mercaptopurine and Methotrexate (6MP/MTX) in This Patient Population.

Quality of life could not be analysed due to the low questionnaire completion rate; only two patients (3%) completed the baseline and 12 month follow up QoL questionnaires, , but data could not be reported in the Outcome Measure due to confidentiality issues.

Spots Global Cancer Trial Database for A Clinical Trial in Patients With Breast Cancer Susceptibility Gene (BRCA) Defective Tumours

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial