Temozolomide as a Prophylaxis Against Brain Recurrence in Participants With Metastatic Breast Cancer (P05225 AM2)

Phase 2

Terminated

• Conditions: Brain Neoplasm; Breast Neoplasm; Second Neoplasm
• Interventions: Drug: temozolomide

• Registration Number: NCT00638963
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

The purpose of this study is to determine whether temozolomide can be used as a prophylaxis against brain recurrence in participants with metastatic breast cancer.

Detailed Description

Breast cancer is the second most common cause of brain metastases. Overall survival after the development of brain metastases tends to be poor (6-8 months). Over-expression of Human Epidermal Growth Factor Receptor 2 (HER-2/neu), negative estrogen receptor, and young age at diagnosis seem to be indicators of high risk for brain metastases. Temozolomide may be a good candidate for prophylactic chemotherapy because of its ability to cross the blood-brain-barrier, achieving high concentrations in the central nervous system (CNS).

Study Timeline

• Study First Submitted: 2008-01-10
• Study First Submitted QC: 2008-03-18
• Study First Posted: 2008-03-19
• Study Start: 2008-10-02
• Primary Completion: 2010-06-30
• Study Completion: 2010-06-30
• Results First Submitted: 2011-06-23
• Results First Submitted QC: 2011-06-23
• Results First Posted: 2011-07-22
• Status Verified: 2017-05
• Last Update Submitted: 2017-05-18
• Last Update Posted: 2017-06-14

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 6

Inclusion Criteria

• Diagnosis of metastatic breast cancer.
• Participants must have completed first line of metastatic chemotherapy and have achieved complete or partial response or disease stability for at least 6 months from the first confirmation of disease stabilization.
• No clinical sign of brain progression.
• At least one of the following 3 conditions: HER2 +++, Young age (< 50 years), and/or estrogen receptor (ER)-/progesterone receptor (PgR)-
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
• Life expectancy ≥3 months.
• Neutrophils ≥1.5 x 10^9/L, platelets ≥100 x 10^9/L, hemoglobin ≥9 g/dL, lymphocytes ≥1 x 10^9/L.
• Bilirubin level either normal or <1.5 x ULN (upper limit of normal).
• AST (aspartate aminotransferase) and ALT (alanine aminotransferase) ≤2.5 x ULN (≤5 x ULN if liver metastases are present).
• Serum creatine <1.5 x ULN.
• Effective contraception if the risk of conception exists.

Exclusion Criteria

• Concurrent chronic systemic immune therapy not indicated in the study protocol.
• Any investigational agent(s) within 4 weeks prior to entry.
• Participants that have completed 2nd, 3rd, or 4th line metastatic chemotherapy or participant in active chemotherapy treatment.
• Clinically relevant coronary artery disease or a history of a myocardial infarction within the last 12 months.
• Acute or sub acute intestinal occlusion or history of inflammatory bowel disease.
• Known Grade 3 or Grade 4 allergic reaction to any of the components of the treatment.
• Known drug abuse/alcohol abuse.
• Legal incapacity or limited legal capacity.
• Medical or psychological condition which in the opinion of the investigator would not permit the participant to complete the study or sign meaningful informed consent.
• Women who are pregnant or breastfeeding.
• Any concurrent malignancy other than non-melanoma skin cancer, or carcinoma in situ of the cervix (participants with a previous malignancy but without evidence of disease for ≥5 years will be allowed to enter the trial).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Temozolomide	temozolomide	-

Primary Outcome Measures

Name	Time	Method
Percent of Participants With Recurrence of Brain Metastases	1 Year	The analysis could not be performed due to low enrollment.

Secondary Outcome Measures

Name	Time	Method
Total Dose of Temozolomide Taken	Baseline to 24 Weeks	This outcome measure was only applicable to the temozolomide arm; the observation arm was therefore not analyzed.
Number of Participants Who Completed the Third Cycle of Treatment	Baseline to 24 Weeks	This outcome measure was only applicable to the temozolomide arm; the observation arm was therefore not analyzed.
Number of Days With Progression-free Survival (PFS)	24, 38, and 52 weeks	PFS was defined as the time interval from randomization to objective tumor progression or death from any cause.; The analysis could not be performed due to low enrollment.
Number of Days With Disease-free Survival (DFS)	24, 38, and 52 weeks	DFS was defined as the time interval from randomization to any relapse (loco-regional, contra-lateral, and/or distant).; The analysis could not be performed due to low enrollment.
Number of Days With Distant Disease-free Survival (DDFS)	24, 38, and 52 weeks	DDFS was defined as the time interval from randomization to only distant metastases (for example, bone, visceral organ, brain).; The analysis could not be performed due to low enrollment.
Number of Days With Brain Recurrence-free Survival (BRFS)	24,38, and 52 weeks	BRFS was defined as the time interval from randomization to the appearance of brain metastases.; The analysis could not be performed due to low enrollment.
Number of Days on Temozolomide Treatment	Baseline to 24 Weeks	This outcome measure was only applicable to the temozolomide arm; the observation arm was therefore not analyzed.
Number of Participants Who Had at Least One Dose Reduction During Treatment	Baseline to 24 Weeks	This outcome measure was only applicable to the temozolomide arm; the observation arm was therefore not analyzed.
Number of Participants Who Had at Least One Treatment Omission During Treatment	Baseline to 24 Weeks	This outcome measure was only applicable to the temozolomide arm; the observation arm was therefore not analyzed.