Endometrial Serous Adenocarcinoma, Stage IIIA Uterine Corpus Cancer, Stage IIIB Uterine Corpus Cancer, Stage IIIC1 Uterine Corpus Cancer, Stage IIIC2 Uterine Corpus Cancer, Stage IVA Uterine Corpus Cancer, Stage IVB Uterine Corpus Cancer
Conditions
Brief summary
This pilot, phase II trial studies the side effects and how well paclitaxel given into the vein and carboplatin given directly into the abdominal cavity (intraperitoneally) followed by radiation therapy work in treating patients with stage IIIC-IV serous uterine cancer. 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, stopping them from dividing, or stopping them from spreading. Giving the drugs in different ways may kill more tumor cells. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving chemotherapy followed by radiation therapy may be an effective treatment for uterine cancer.
Detailed description
PRIMARY OBJECTIVES: I. To evaluate the toxicity (as defined by National Cancer Institute \[NCI\] Common Toxicity Criteria version \[v.\] 4.0) of weekly intravenous (IV) paclitaxel with intraperitoneal (IP) carboplatin chemotherapy given every third week, followed by radiation therapy (RT) in patients with advanced stage uterine serous cancer (USC). II. To determine the feasibility of this regimen in women with advanced stage USC. SECONDARY OBJECTIVES: I. To assess the frequency and the reasons for early discontinuation of the study treatments. II. To describe patient-reported quality of life parameters at specified time points during the study using validated questionnaires: European Organization for Research and the Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 and QLQ-ovarian cancer module (OV)28. TERTIARY OBJECTIVES: I. To define patterns of recurrence (e.g. local versus distant) and progression-free survival in patients with advanced and recurrent USC treated with dose dense IV paclitaxel and IP carboplatin therapy. II. To correlate surrogate endpoint biomarkers that is performed in standard histology processing (estrogen receptor and progesterone receptor status as well as human epidermal growth factor 2 \[Her2/neu\] status) with progression-free survival and prognosis. III. To assess the potential late effects of combined intraperitoneal chemotherapy and radiotherapy on the gastrointestinal, genitoureteral, bone marrow and other body systems beginning at 6 months post treatment completion during routine office visits. OUTLINE: CHEMOTHERAPY: Patients receive paclitaxel intravenously (IV) over 1 hour on days 1, 8, and 15 and carboplatin intraperitoneally (IP) on day 1. Treatment repeats every 21 days for up to 6 courses (weeks 1-18) in the absence of disease progression or unacceptable toxicity. RADIATION: At provider discretion, patients may undergo 3-dimensional (3D) conformal or intensity-modulated radiation therapy (IMRT) 5 days a week for 5 weeks (weeks 19-23). After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then yearly thereafter for up to 10 years.
Interventions
DRUGPaclitaxel
Given IV
DRUGCarboplatin
Given IP
RADIATION3-Dimensional Conformal Radiation Therapy
Undergo 3D conformal radiation therapy
RADIATIONIntensity-Modulated Radiation Therapy
Undergo IMRT
OTHERQuality-of-Life Assessment
Ancillary studies
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
* Histological/cytologically documented primary International Federation of Gynecology and Obstetrics (FIGO) stage 3C1, 3C2, stage 4A, and 4B uterine serous carcinoma; in addition, certain stage 3A and B disease are also allowed * Residual disease after primary surgery: * Eligible: * Stage 3A and B (pelvic, but confined to adnexa or vagina), residual disease present * Stage 3CI (pelvic node positive) * Stage 3CII (para-aortic node positive) * Stage 4A (bladder or pelvic bowel) * Stage 4B (distant metastases \[mets\] including abdominal mets), completely resected * Not eligible * Stage 3A and B (pelvic, but confined to adnexa or vagina), completely resected * Stage 4B (distant mets including abdominal mets), residual disease present * All patients must have a procedure for determining diagnosis of high-risk uterine cancer (HRUC); minimum surgical intervention required is tissue biopsy (may be from endometrium), if significant clinical evidence exists to support a stage 3 or 4 diagnosis; as per the discretion of the surgeon, complete surgical staging should include: total abdominal hysterectomy, bilateral salpingo-oophorectomy, peritoneal washings, omental biopsy and lymph node samplings; this is typically the standard unless the disease is bulky or the clinician feels the patient would be best served by chemotherapy and radiation therapy after histologic diagnosis is confirmed * Eastern Cooperative Oncology Group (ECOG) performance status of =\< 2 * Written voluntary informed consent
Exclusion criteria
* Distant metastasis to the lung, bone or brain; typically, most stage 4 uterine papillary serous cancer (UPSC) is confined to the abdomen on presentation * Serum glutamic oxaloacetic transaminase (SGOT) and/or serum glutamate pyruvate transaminase (SGPT) \> 2.5 times the institutional upper limit of normal (ULN) * Total serum bilirubin \> 1.5 mg/dl * 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) * History of abdominal/pelvic radiation therapy * Severe or uncontrolled, concurrent medical disease (e.g. uncontrolled diabetes, unstable angina, myocardial infarction within 6 months, congestive heart failure, etc.) * Patients with dementia or altered mental status that would prohibit the giving and understanding of informed consent at the time of study entry
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Degree of Tolerability, Estimated by the Proportion of Participants Who Complete 6 Treatment Cycles of IP Carboplatin | Up to 18 weeks | At the end of the study, the proportion of patients who tolerated the therapy will be estimated, along with corresponding 95% confidence intervals. Reasons for discontinuation of therapy will be categorized and summarized by computing frequencies. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | The duration of time from start of treatment to time of progression, or death, whichever happens first, assessed at 1 year | The proportion of responders at one year will be estimated with the Kaplan-Meier method. Surrogate endpoint biomarkers including estrogen, progesterone, and Her2/neu receptor status will be correlated with progression-free survival using the Cox Proportional Hazards model, provided the availability of a sufficient number of events. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited and enrolled into the study between. The 1st participant was enrolled on 4/10/2014 and the final participant was enrolled into the study on 4/5/2016. No further participants have been enrolled since April 2016.
Pre-assignment details
4 participants consented but only 3 were enrolled. One participant failed screening due to the onset of an adverse event.
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Paclitaxel, Carboplatin, Radiotherapy) CHEMOTHERAPY: Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15 and carboplatin IP on day 1. Treatment repeats every 21 days for up to 6 courses (weeks 1-18) in the absence of disease progression or unacceptable toxicity.
RADIATION: At provider discretion, patients may undergo 3D conformal or IMRT 5 days a week for 5 weeks (weeks 19-23).
Paclitaxel: Given IV
Carboplatin: Given IP
3-Dimensional Conformal Radiation Therapy: Undergo 3D conformal radiation therapy
Intensity-Modulated Radiation Therapy: Undergo IMRT
Quality-of-Life Assessment: Ancillary studies
Laboratory Biomarker Analysis: Correlative studies | 4 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Treatment (Paclitaxel, Carboplatin, Radiotherapy) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment United States | 4 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 4 |
| other Total, other adverse events | 1 / 4 |
| serious Total, serious adverse events | 2 / 4 |
Outcome results
Primary
Degree of Tolerability, Estimated by the Proportion of Participants Who Complete 6 Treatment Cycles of IP Carboplatin
At the end of the study, the proportion of patients who tolerated the therapy will be estimated, along with corresponding 95% confidence intervals. Reasons for discontinuation of therapy will be categorized and summarized by computing frequencies.
Time frame: Up to 18 weeks
Population: Data was not collected/aggregated and therefore not analyzed for Degree of Tolerability
Secondary
Progression-free Survival
The proportion of responders at one year will be estimated with the Kaplan-Meier method. Surrogate endpoint biomarkers including estrogen, progesterone, and Her2/neu receptor status will be correlated with progression-free survival using the Cox Proportional Hazards model, provided the availability of a sufficient number of events.
Time frame: The duration of time from start of treatment to time of progression, or death, whichever happens first, assessed at 1 year
Population: Data was not collected/aggregated and therefore not analyzed for Progression Free Survival