Endometrial Adenocarcinoma, Stage IA Uterine Corpus Cancer, Stage IB Uterine Corpus Cancer, Stage II Uterine Corpus Cancer, Stage IIIA Uterine Corpus Cancer, Stage IIIB Uterine Corpus Cancer, Stage IIIC Uterine Corpus Cancer, Stage IVA Uterine Corpus Cancer, Stage IVB Uterine Corpus Cancer
Conditions
Brief summary
This phase II trial studies how well radiation therapy, paclitaxel, and carboplatin work in treating patients with high-risk endometrial cancer. Radiation therapy uses high energy x rays to kill tumor cells. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing or by stopping them from spreading. Giving radiation therapy with chemotherapy may kill more tumor cells.
Detailed description
PRIMARY OBJECTIVES: I. To evaluate progression-free survival. II. To assess and document location of disease recurrence (distant vs local vs both) using this treatment regimen. II. To evaluate the toxicity of radiation therapy sandwiched between cycles of paclitaxel/carboplatin chemotherapy in patients with high-risk endometrial cancer. III. To evaluate the associations of cancer recurrence with tumor tissue expression levels of insulin-like growth factor-I (IGF-I), IGF-II, insulin-like growth factor binding protein 1 (IGFBP-1) and -3, insulin receptor, IGF-I receptor, estrogen receptor, and progesterone receptor. OUTLINE: CHEMOTHERAPY (weeks 1-9, 13-21): Patients receive paclitaxel intravenously (IV) over 3 hours and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 3 courses during weeks 1-9 and 3 courses during weeks 13-21. RADIATION THERAPY (weeks 8-13 or 8-15): Patients with stage I disease undergo high dose rate (HDR) brachytherapy once weekly for a total of 5 fractions during weeks 8-13. All other patients undergo external beam radiation therapy (EBRT) once daily (QD) 5 days a week for a total of 25 fractions during weeks 8-12 and HDR brachytherapy once weekly for a total of 3 fractions during weeks 13-15. After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.
Interventions
DRUGPaclitaxel
Given IV
DRUGCarboplatin
Given IV
RADIATIONInternal Radiation Therapy
Undergo HDR brachytherapy
RADIATIONExternal Beam Radiation Therapy
Undergo EBRT
OTHERLaboratory Biomarker Analysis
Correlative studies
Sponsors
National Cancer Institute (NCI)
Albert Einstein College of Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically-documented high-risk endometrioid adenocarcinoma with no visible residual disease, defined by the following criteria: * Surgical stage I disease with \< 50 myometrial invasion and grade 3 tumor (IAG3) with lymphovascular space involvement; * Surgical stage I disease with \>= 50% myometrial invasion and grade 2 or 3 tumor (IBG2, IBG3); * Any surgical stage II disease (II); * Any surgical stage III disease (IIIA, IIIB, IIIC); and * Any surgical stage IV disease with no residual macroscopic tumor * Surgical staging to include total abdominal hysterectomy, bilateral salpingo-oophorectomy, peritoneal washings, and lymph node samplings as per standard Gynecologic Oncology Group (GOG) criteria * Eastern Cooperative Oncology Group (ECOG) performance status of \< 2 * Written voluntary informed consent
Exclusion criteria
* Serum glutamic oxaloacetic transaminase (SGOT) and/or serum glutamate pyruvate transaminase (SGPT) \> 2.5 times the institutional upper limit of normal * Total serum bilirubin \> 1.5 mg/dl * History of chronic or active hepatitis * Serum creatinine \> 2.0 mg/dl * Platelets \< 100,000/mm\^3 * Absolute neutrophil count (ANC) \< 1500/mm\^3 * Hemoglobin \< 8.0 g/dl (the patient may be transfused prior to study entry) * Patient has severe or uncontrolled concurrent medical disease (e.g. uncontrolled diabetes, unstable angina, myocardial infarction within 6 months, congestive heart failure, etc.) * Patient with any prior chemotherapy or radiotherapy for pelvic malignancy * Patients with dementia or altered mental status that would prohibit the giving and understanding of informed consent at the time of study entry * Patients with any history of cancer with the exception of non-melanoma skin cancer are excluded if there is any evidence of other malignancy being present within the past five years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | From randomization until documented tumor recurrence or death from any cause, assessed up to 5 years | PFS will be analyzed using standard survival analytic methods, including the Kaplan-Meier approach for estimating the survival distribution. Median time to progression and 95% confidence intervals will be estimated from the Kaplan-Meier curves. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Expression Levels of IGF-2 | Up to 5 years | Associations of PFS with tumor tissue expression levels of IGF-2 will be evaluated. Provided the number of events is sufficient, Cox proportional hazards models will be fit to the data to explore these associations. |
| Expression Levels of IGFBP-1 | Up to 5 years | Associations of PFS with tumor tissue expression levels of IGFBP-1 will be evaluated. Provided the number of events is sufficient, Cox proportional hazards models will be fit to the data to explore these associations. |
| Expression Levels of IGFBP-3 | Up to 5 years | Associations of PFS with tumor tissue expression levels of IGFBP-3 will be evaluated. Provided the number of events is sufficient, Cox proportional hazards models will be fit to the data to explore these associations. |
| Expression Levels of IGF-1 | Up to 5 years | Associations of PFS with tumor tissue expression levels of IGF-1 will be evaluated. Provided the number of events is sufficient, Cox proportional hazards models will be fit to the data to explore these associations. |
| Expression Levels of IGF-1 Receptor | Up to 5 years | Associations of PFS with tumor tissue expression levels of IGF-1 receptor will be evaluated. Provided the number of events is sufficient, Cox proportional hazards models will be fit to the data to explore these associations. |
| Expression Levels of Estrogen Receptor | Up to 5 years | Associations of PFS with tumor tissue expression levels of estrogen receptor will be evaluated. Provided the number of events is sufficient, Cox proportional hazards models will be fit to the data to explore these associations. |
| Expression Levels of Progesterone Receptor | Up to 5 years | Associations of PFS with tumor tissue expression levels of progesterone receptor will be evaluated. Provided the number of events is sufficient, Cox proportional hazards models will be fit to the data to explore these associations. |
| Expression Levels of Insulin Receptor | Up to 5 years | Associations of PFS with tumor tissue expression levels of insulin receptor will be evaluated. Provided the number of events is sufficient, Cox proportional hazards models will be fit to the data to explore these associations. |
Countries
United States
Participant flow
Recruitment details
31 participants were enrolled into the study between 1/16/2009 (date the first participant was enrolled) and 6/3/2019 (date final participant was enrolled)
Pre-assignment details
40 participants were recruited. Of the 40 participants, 1 participant was not consented and 8 participants screen failed. 31 participants were enrolled and randomized into the study.
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Paclitaxel, Carboplatin, Radiation Therapy) CHEMOTHERAPY (weeks 1-9, 13-21): Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 3 courses during weeks 1-9 and 3 courses during weeks 13-21.
RADIATION THERAPY (weeks 8-13 or 8-15): Patients with stage I disease undergo HDR brachytherapy once weekly for a total of 5 fractions during weeks 8-13. All other patients undergo EBRT QD 5 days a week for a total of 25 fractions during weeks 8-12 and HDR brachytherapy once weekly for a total of 3 fractions during weeks 13-15.
Paclitaxel: Given IV
Carboplatin: Given IV
Internal Radiation Therapy: Undergo HDR brachytherapy
External Beam Radiation Therapy: Undergo EBRT
Laboratory Biomarker Analysis: Correlative studies | 31 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 4 |
| Overall Study | Delayed Radiation Therapy | 1 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Treatment (Paclitaxel, Carboplatin, Radiation Therapy) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 8 Participants |
| Age, Categorical Between 18 and 65 years | 23 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants |
| Race (NIH/OMB) White | 12 Participants |
| Region of Enrollment United States | 31 participants |
| Sex: Female, Male Female | 31 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 31 |
| other Total, other adverse events | 5 / 31 |
| serious Total, serious adverse events | 2 / 31 |
Outcome results
Primary
Progression-free Survival (PFS)
PFS will be analyzed using standard survival analytic methods, including the Kaplan-Meier approach for estimating the survival distribution. Median time to progression and 95% confidence intervals will be estimated from the Kaplan-Meier curves.
Time frame: From randomization until documented tumor recurrence or death from any cause, assessed up to 5 years
Population: PFS data was not collected and analyzed.
Secondary
Expression Levels of Estrogen Receptor
Associations of PFS with tumor tissue expression levels of estrogen receptor will be evaluated. Provided the number of events is sufficient, Cox proportional hazards models will be fit to the data to explore these associations.
Time frame: Up to 5 years
Population: Estrogen receptor expression data was not collected and analyzed.
Secondary
Expression Levels of IGF-1
Associations of PFS with tumor tissue expression levels of IGF-1 will be evaluated. Provided the number of events is sufficient, Cox proportional hazards models will be fit to the data to explore these associations.
Time frame: Up to 5 years
Population: IGF-1 expression data was not collected and analyzed.
Secondary
Expression Levels of IGF-1 Receptor
Associations of PFS with tumor tissue expression levels of IGF-1 receptor will be evaluated. Provided the number of events is sufficient, Cox proportional hazards models will be fit to the data to explore these associations.
Time frame: Up to 5 years
Population: IGF-1 receptor expression data was not collected and analyzed.
Secondary
Expression Levels of IGF-2
Associations of PFS with tumor tissue expression levels of IGF-2 will be evaluated. Provided the number of events is sufficient, Cox proportional hazards models will be fit to the data to explore these associations.
Time frame: Up to 5 years
Population: IGF-2 expression data was not collected and analyzed.
Secondary
Expression Levels of IGFBP-1
Associations of PFS with tumor tissue expression levels of IGFBP-1 will be evaluated. Provided the number of events is sufficient, Cox proportional hazards models will be fit to the data to explore these associations.
Time frame: Up to 5 years
Population: IGFBP-1 expression data was not collected and analyzed.
Secondary
Expression Levels of IGFBP-3
Associations of PFS with tumor tissue expression levels of IGFBP-3 will be evaluated. Provided the number of events is sufficient, Cox proportional hazards models will be fit to the data to explore these associations.
Time frame: Up to 5 years
Population: IGFBP-3 expression data was not collected and analyzed.
Secondary
Expression Levels of Insulin Receptor
Associations of PFS with tumor tissue expression levels of insulin receptor will be evaluated. Provided the number of events is sufficient, Cox proportional hazards models will be fit to the data to explore these associations.
Time frame: Up to 5 years
Population: Insulin receptor expression data was not collected and analyzed.
Secondary
Expression Levels of Progesterone Receptor
Associations of PFS with tumor tissue expression levels of progesterone receptor will be evaluated. Provided the number of events is sufficient, Cox proportional hazards models will be fit to the data to explore these associations.
Time frame: Up to 5 years
Population: Progesterone receptor expression data was not collected and analyzed.