Brain Neoplasm, Breast Neoplasm, Second Neoplasm
Conditions
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).
Interventions
DRUGtemozolomide
Capsules to equal 75 mg/m\^2, orally, daily for 6 weeks, in 3 eight-week cycles
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Participants With Recurrence of Brain Metastases | 1 Year | The analysis could not be performed due to low enrollment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 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 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. |
| 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. |
| 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. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Temozolomide Capsules to equal 75 mg/m\^2, orally, daily for 6 weeks, in 3 eight-week cycles | 3 |
| Observational No temozolomide treatment | 3 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Temozolomide | Observational | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 3 Participants | 6 Participants |
| Region of Enrollment Italy | 3 participants | 3 participants | 6 participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 3 | 2 / 3 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 |
Outcome results
Primary
Percent of Participants With Recurrence of Brain Metastases
The analysis could not be performed due to low enrollment.
Time frame: 1 Year
Secondary
Number of Days on Temozolomide Treatment
This outcome measure was only applicable to the temozolomide arm; the observation arm was therefore not analyzed.
Time frame: Baseline to 24 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Temozolomide | Number of Days on Temozolomide Treatment | 75 Days | Standard Deviation 65.82 |
Secondary
Number of Days With Brain Recurrence-free Survival (BRFS)
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.
Time frame: 24,38, and 52 weeks
Secondary
Number of Days With Disease-free Survival (DFS)
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.
Time frame: 24, 38, and 52 weeks
Secondary
Number of Days With Distant Disease-free Survival (DDFS)
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.
Time frame: 24, 38, and 52 weeks
Secondary
Number of Days With Progression-free Survival (PFS)
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.
Time frame: 24, 38, and 52 weeks
Secondary
Number of Participants Who Completed the Third Cycle of Treatment
This outcome measure was only applicable to the temozolomide arm; the observation arm was therefore not analyzed.
Time frame: Baseline to 24 Weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Temozolomide | Number of Participants Who Completed the Third Cycle of Treatment | 2 Participants |
Secondary
Number of Participants Who Had at Least One Dose Reduction During Treatment
This outcome measure was only applicable to the temozolomide arm; the observation arm was therefore not analyzed.
Time frame: Baseline to 24 Weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Temozolomide | Number of Participants Who Had at Least One Dose Reduction During Treatment | 3 Participants |
Secondary
Number of Participants Who Had at Least One Treatment Omission During Treatment
This outcome measure was only applicable to the temozolomide arm; the observation arm was therefore not analyzed.
Time frame: Baseline to 24 Weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Temozolomide | Number of Participants Who Had at Least One Treatment Omission During Treatment | 2 Participants |
Secondary
Total Dose of Temozolomide Taken
This outcome measure was only applicable to the temozolomide arm; the observation arm was therefore not analyzed.
Time frame: Baseline to 24 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Temozolomide | Total Dose of Temozolomide Taken | 9791.9 Milligrams | Standard Deviation 8732 |