Endometrial Cancer
Conditions
Keywords
Uterine serous papillary carcinoma, Type II endometrial cancer, HER2/neu, Paclitaxel, Carboplatin, Trastuzumab
Brief summary
The primary objective of this study is to estimate whether the addition of trastuzumab to paclitaxel and carboplatin chemotherapy improves progression free survival when compared to paclitaxel and carboplatin alone in Uterine Serous Papillary Carcinoma (USPC) patients overexpressing Her2/neu at 3+ level by immunohistochemistry (IHC)or positive by fluorescence in situ hybridization (FISH).
Detailed description
The purpose of this study is to perform a randomized Phase II evaluation of Carboplatin/Paclitaxel with or without Trastuzumab (Herceptin) in patients with HER2/neu+ advanced stage/recurrent disease with an emphasis on determining the progression free survival in USPC patients and assessing immunologic markers predictive of trastuzumab response.
Interventions
Paclitaxel 175 mg/m2 will administered intravenously every 21 days for 6 cycles. Carboplatin AUC 5 will be administered intravenously every 21 days for 6 cycles. 100% of patients will receive Carboplatin/Paclitaxel.
DRUGTrastuzumab
Paclitaxel 175 mg/m2 will be administered intravenously every 21 days for 6 cycles. Carboplatin AUC 5 will be administered intravenously every 21 days for 6 cycles. On day 1, an 8 mg/kg loading dose of trastuzumab will be administered over a 90 minute period. Beginning on day 21, patients will receive 6mg/kg of trastuzumab, administered intravenously every 21 days and continued indefinitely every 21 days after 6 cycles of cytotoxic therapy are completed and until progression of the disease or prohibitive toxicities occur. 50% of patients will receive Carboplatin/Paclitaxel with the addition of Trastuzumab.
Sponsors
Genentech, Inc.
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Healthy volunteers
No
Inclusion criteria
* Patients must have advanced (stage III-IV) or recurrent histologically confirmed USPC with measurable disease. * Patients must harbor a tumor HER2/neu+ based upon IHC staining score of 3+ or 2+ with confirmed gene amplification by FISH
Exclusion criteria
* Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancers, significant history of cardiac disease, uncontrolled hypertension, unstable medical issue, brain leptomeningeal, prior therapy with trastuzumab, uncontrolled seizure disorder, seropositive for HIV, active hepatitis, hemorrhagic diathesis or requiring supplemental oxygen.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival Differences Between Treatment Arms. | 6 years | Progression free survival differences between treatment arms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To Assess the Safety Profile of Trastuzumab in USPC Patients by CTCAE v4.0 | 6 years | To assess the safety profile of trastuzumab in USPC patients by CTCAE v4.0. Presented are counts of those that experience any Serious Adverse Events or All Other Adverse Events. |
| To Assess Objective Response Rate (ORR) | 6 years | To assess objective response rate (ORR) |
| To Assess Overall Survival (OS) | 6 years | To assess overall survival (OS), presented are the number of participants that survived through the duration of the study period. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Carboplatin/Paclitaxel Chemotherapy
Carboplatin/Paclitaxel: Paclitaxel 175 mg/m2 will administered intravenously every 21 days for 6 cycles. Carboplatin AUC 5 will be administered intravenously every 21 days for 6 cycles. 100% of patients will receive Carboplatin/Paclitaxel. | 28 |
| Trastuzumab Monoclonal antibody
Trastuzumab: Paclitaxel 175 mg/m2 will be administered intravenously every 21 days for 6 cycles. Carboplatin AUC 5 will be administered intravenously every 21 days for 6 cycles. On day 1, an 8 mg/kg loading dose of trastuzumab will be administered over a 90 minute period. Beginning on day 21, patients will receive 6mg/kg of trastuzumab, administered intravenously every 21 days and continued indefinitely every 21 days after 6 cycles of cytotoxic therapy are completed and until progression of the disease or prohibitive toxicities occur. 50% of patients will receive Carboplatin/Paclitaxel with the addition of Trastuzumab. | 30 |
| Total | 58 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 0 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Carboplatin/Paclitaxel | Trastuzumab | Total |
|---|---|---|---|
| Age, Continuous | 73 years | 67 years | 69 years |
| Disease Status Advanced | 20 Participants | 21 Participants | 41 Participants |
| Disease Status Recurrent | 8 Participants | 9 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 3 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 26 Participants | 26 Participants | 52 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 10 Participants | 18 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 17 Participants | 20 Participants | 37 Participants |
| Region of Enrollment United States | 28 participants | 30 participants | 58 participants |
| Sex: Female, Male Female | 28 Participants | 30 Participants | 58 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 | 21 / 28 | 21 / 32 |
| other Total, other adverse events | 28 / 28 | 32 / 32 |
| serious Total, serious adverse events | 6 / 28 | 14 / 32 |
Outcome results
Primary
Progression Free Survival Differences Between Treatment Arms.
Progression free survival differences between treatment arms.
Time frame: 6 years
Population: Only patients eligible to be assessed for progression free survival.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Carboplatin/Paclitaxel | Progression Free Survival Differences Between Treatment Arms. | 8.049 months |
| Trastuzumab | Progression Free Survival Differences Between Treatment Arms. | 12.945 months |
Secondary
To Assess Objective Response Rate (ORR)
To assess objective response rate (ORR)
Time frame: 6 years
Population: Among those with recurrent disease- see baseline characteristics table.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Carboplatin/Paclitaxel | To Assess Objective Response Rate (ORR) | Complete Response (CR) | 2 Participants |
| Carboplatin/Paclitaxel | To Assess Objective Response Rate (ORR) | Partial Response (PR) | 4 Participants |
| Carboplatin/Paclitaxel | To Assess Objective Response Rate (ORR) | Stable Disease (SD) | 1 Participants |
| Carboplatin/Paclitaxel | To Assess Objective Response Rate (ORR) | Progressive Disease (PD) | 1 Participants |
| Trastuzumab | To Assess Objective Response Rate (ORR) | Progressive Disease (PD) | 0 Participants |
| Trastuzumab | To Assess Objective Response Rate (ORR) | Complete Response (CR) | 1 Participants |
| Trastuzumab | To Assess Objective Response Rate (ORR) | Stable Disease (SD) | 5 Participants |
| Trastuzumab | To Assess Objective Response Rate (ORR) | Partial Response (PR) | 3 Participants |
Secondary
To Assess Overall Survival (OS)
To assess overall survival (OS), presented are the number of participants that survived through the duration of the study period.
Time frame: 6 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Carboplatin/Paclitaxel | To Assess Overall Survival (OS) | 7 Participants |
| Trastuzumab | To Assess Overall Survival (OS) | 9 Participants |
Secondary
To Assess the Safety Profile of Trastuzumab in USPC Patients by CTCAE v4.0
To assess the safety profile of trastuzumab in USPC patients by CTCAE v4.0. Presented are counts of those that experience any Serious Adverse Events or All Other Adverse Events.
Time frame: 6 years
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Carboplatin/Paclitaxel | To Assess the Safety Profile of Trastuzumab in USPC Patients by CTCAE v4.0 | Serious Adverse Events | 6 Participants |
| Carboplatin/Paclitaxel | To Assess the Safety Profile of Trastuzumab in USPC Patients by CTCAE v4.0 | All Other Adverse Events | 28 Participants |
| Trastuzumab | To Assess the Safety Profile of Trastuzumab in USPC Patients by CTCAE v4.0 | Serious Adverse Events | 14 Participants |
| Trastuzumab | To Assess the Safety Profile of Trastuzumab in USPC Patients by CTCAE v4.0 | All Other Adverse Events | 32 Participants |