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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2016 by Albert Einstein College of Medicine of Yeshiva University
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Dennis Yi-Shin Kuo, Albert Einstein College of Medicine of Yeshiva University
ClinicalTrials.gov Identifier:
NCT01041027
First received: December 29, 2009
Last updated: January 11, 2016
Last verified: January 2016
  Purpose
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.

Condition Intervention Phase
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
Drug: Paclitaxel
Drug: Carboplatin
Radiation: Internal Radiation Therapy
Radiation: External Beam Radiation Therapy
Other: Laboratory Biomarker Analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Albert Einstein College of Medicine of Yeshiva University:

Primary Outcome Measures:
  • Progression-free survival (PFS) [ Time Frame: From randomization until documented tumor recurrence or death from any cause, assessed up to 5 years ] [ Designated as safety issue: No ]
    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 Outcome Measures:
  • Expression levels of IGF-1 [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    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-2 [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    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 insulin receptor [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    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.

  • Expression levels of IGF-1 receptor [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 25
Study Start Date: September 2008
Estimated Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.

Drug: Paclitaxel
Given IV
Other Names:
  • Anzatax
  • TAX
Drug: Carboplatin
Given IV
Radiation: Internal Radiation Therapy
Undergo HDR brachytherapy
Other Names:
  • Brachytherapy
  • Internal Radiation
  • Internal Radiation Brachytherapy
  • Radiation Brachytherapy
Radiation: External Beam Radiation Therapy
Undergo EBRT
Other Names:
  • Definitive Radiation Therapy
  • EBRT
  • External Beam RT
Other: Laboratory Biomarker Analysis
Correlative studies

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

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01041027

Locations
United States, New York
Albert Einstein College of Medicine Recruiting
Bronx, New York, United States, 10461
Contact: Dennis Y. Kuo    718-405-8082    dykuo@montefiore.org   
Principal Investigator: Dennis Y. Kuo         
Sponsors and Collaborators
Albert Einstein College of Medicine of Yeshiva University
National Cancer Institute (NCI)
Investigators
Principal Investigator: Dennis Kuo Albert Einstein College of Medicine of Yeshiva University
  More Information

Responsible Party: Dennis Yi-Shin Kuo, Principal Investigator, Albert Einstein College of Medicine of Yeshiva University
ClinicalTrials.gov Identifier: NCT01041027     History of Changes
Other Study ID Numbers: 08-03-060  NCI-2013-01224  07-062  NCI-2012-00458  08-03-060  P30CA013330 
Study First Received: December 29, 2009
Last Updated: January 11, 2016
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Adenocarcinoma
Endometrial Neoplasms
Uterine Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Uterine Diseases
Genital Diseases, Female
Paclitaxel
Albumin-Bound Paclitaxel
Carboplatin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 21, 2016