Radiation Therapy, Paclitaxel, and Carboplatin in Treating Patients With High-Risk Endometrial Cancer

Albert Einstein College of Medicine

Status and phase: Terminated; Phase 2

Conditions: Endometrial Adenocarcinoma; Stage IIIB Uterine Corpus Cancer; Stage IIIA Uterine Corpus Cancer; Stage II Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer; Stage IVA Uterine Corpus Cancer; Stage IIIC Uterine Corpus Cancer; Stage IA Uterine Corpus Cancer; Stage IB Uterine Corpus Cancer

Treatments: Drug: Carboplatin; Radiation: External Beam Radiation Therapy; Drug: Paclitaxel; Radiation: Internal Radiation Therapy; Other: Laboratory Biomarker Analysis

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01041027

NCI-2012-00458

07-062

P30CA013330 (U.S. NIH Grant/Contract)

NCI-2013-01224 (Registry Identifier)

08-03-060 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 31 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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31 participants in 1 patient group

Treatment (paclitaxel, carboplatin, radiation therapy)

Experimental group

Description:

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.

Treatment:

Drug: Carboplatin

Radiation: Internal Radiation Therapy

Drug: Paclitaxel

Radiation: External Beam Radiation Therapy

Other: Laboratory Biomarker Analysis