Clinical trial NCT01041027: Radiation Therapy, Paclitaxel, and Carboplatin in Treating Patients With High-Risk Endometrial Cancer
Official title: A Pilot Phase II Trial of Radiation Therapy "Sandwiched" Between Paclitaxel and Carboplatin in Patients With High-Risk Endometrial Cancer After Standard Surgical Staging
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: 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
Lead sponsor: Albert Einstein College of Medicine
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2009-12-30
Enrollment: 31
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: From randomization until documented tumor recurrence or death from any cause, assessed up to 5 years
Secondary outcomes:
measure: Expression Levels of IGF-1
timeFrame: Up to 5 years
measure: Expression Levels of IGF-2
timeFrame: Up to 5 years
measure: Expression Levels of IGFBP-1
timeFrame: Up to 5 years
measure: Expression Levels of IGFBP-3
timeFrame: Up to 5 years
measure: Expression Levels of Insulin Receptor
timeFrame: Up to 5 years
measure: Expression Levels of IGF-1 Receptor
timeFrame: Up to 5 years
measure: Expression Levels of Estrogen Receptor
timeFrame: Up to 5 years
measure: Expression Levels of Progesterone Receptor
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Bronx
country: United States
facility: Albert Einstein College of Medicine
state: New York
Study officials:
affiliation: Albert Einstein College of Medicine
name: Dennis Yi-Shin Kuo
role: PRINCIPAL_INVESTIGATOR
References: