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A Phase II Evaluation of Docetaxel and Carboplatin Followed by Tumor Volume Directed Pelvic Irradiation

This study has been completed.
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
Carilion Clinic
ClinicalTrials.gov Identifier:
NCT00285415
First received: January 31, 2006
Last updated: October 24, 2013
Last verified: October 2013
  Purpose

The purpose of this study is to determine the effectiveness of the combination of the two drugs, docetaxel (Taxotere®) and carboplatin (Paraplatin®) followed by radiation directed at the tumor in treating your endometrial cancer.


Condition Intervention Phase
Advanced Endometrial Adenocarcinoma, Stage III A, B, C
Drug: Docetaxel and Carboplatin
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Evaluation of Docetaxel and Carboplatin Followed by Tumor Volume Directed Pelvic Plus or Minus Para-Aortic Irradiation for Stage III/IV Endometrial Carcinoma

Resource links provided by NLM:


Further study details as provided by Carilion Clinic:

Primary Outcome Measures:
  • to estimate the overall response rate (ORR) for women with newly diagnosed stages III-IV or recurrent endometrial carcinoma treated with docetaxel and carboplatin followed by tumor volume directed pelvic plus or minus para-aortic irradiation. [ Time Frame: 6 cycles of chemotherapy followed by radiation therapy ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To estimate the progressive free survival (PFS) [ Time Frame: every 3 months for 2 years and then every 6 months for 3 years. Yearly after 5 years. ] [ Designated as safety issue: No ]
  • To estimate overall survival (OS) [ Time Frame: every 3 months for 2 years then every 6 months for 3 years ] [ Designated as safety issue: No ]
  • To evaluate the safety and tolerability profile of this regimen [ Time Frame: during treatment ] [ Designated as safety issue: No ]

Enrollment: 46
Study Start Date: April 2005
Study Completion Date: June 2012
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1 Drug: Docetaxel and Carboplatin
docetaxel (75 mg/m2) + carboplatin (AUC 6) IV every 3 weeks X 6 cycles

  Hide Detailed Description

Detailed Description:

Endometrial carcinoma is the most common malignancy in the female reproductive tract. For the percentage of patients with advanced stage (III - IV) optimum adjuvant therapy status-post surgical staging and/or optimal cytoreductive surgery is not well defined and limited in the rates of response. Survival rates range from 18 - 49% with high levels of toxicity with the current treatment regimens.(1)

The Gynecologic Oncology Group (GOG) explored the use of chemotherapy in protocol #107 comparing adriamycin with a combination of adriamycin and cisplatin.(2) This trial boasted a 45% response rate for the combination arm compared to a 27% response rate in the adriamycin only arm. Although no difference was seen in overall survival, the combination arm showed an improvement in progression free survival from 3.8 to 5.7 months. Subsequently, GOG protocol #122 randomized patients to this chemotherapeutic regimen versus whole abdominal radiation therapy. This trial is now closed to accrual and results are pending.

Ball et. al. reported on a phase II trial of paclitaxel in advanced or recurrent endometrial cancer done through the GOG.(3) At 250 mg/m2 (200mg/m2 for patients with previous radiation therapy) over 24 hours, every 21 days, 10/28 patients responded. There were 4 complete responders and 6 partial responders with an overall response rate of 35.7%. Toxicity was remarkably high with grade 3 and 4 neutropenia and neurotoxicity seen in 62% and 10.7%, respectively.

Dimpoulos et. al. reported the use of paclitaxel 175 mg/m2 over 3 hours and cisplatin 75mg/m2 every 21 days in advanced or recurrent endometrial carcinoma.(4) A 67% objective response rate was seen with 29% showing a complete response and 38% partial response. Toxicities included a 9%

grade 3 and 4 peripheral neuropathy rate. These response rates changed the standard of care in the community setting from the more toxic regimen of adriamycin and cisplatin to paclitaxel and carboplatin.

Hoskins et. al. substituted carboplatin for cisplatin in an effort to reduce the peripheral neuropathy seen in the Dimpoulos trial. This phase II combination of paclitaxel and carboplatin with radiation therapy in advanced endometrial cancer resulted in a 75% response rate. The median failure-free survival time was 23 months, with a 62% 3-year overall survival rate. Toxicities were primarily hematologic and reversible.(5)

The ongoing GOG protocol, #184, is exploring the combination of tumor directed radiation followed by a randomization to adriamycin and cisplatin versus adriamycin, cisplatin and paclitaxel with G-CSF support. Increased toxicity will be expected in the three-drug regimen. With a significant response rates to a combination of paclitaxel and carboplatin along with radiation therapy in the phase II setting it is hard to justify the added toxicity of this three-drug regimen.

The SCOTROC phase III trial comparing docetaxel (75 mg/m2) over 1 hour plus carboplatin (AUC 6) vs. paclitaxel (175 mg/m2) over 3 hours plus carboplatin (AUC 6) yielded equivalent overall response rates in 1,077 patients with ovarian cancer.(6) The docetaxel arm resulted in significantly less overall grade 2 and 3 sensory and motor neurotoxicity. Only 4 patients withdrew from the trial due to neurotoxicity on the docetaxel arm vs. 32 patients on the paclitaxel arm. However, the docetaxel arm resulted in a higher incidence of neutropenia and associated complications without compromising treatment delivery of overall safety.

Based on the information to date, it seems prudent to explore a phase II trial of docetaxel plus carboplatin every 3 weeks for 6 cycles followed by radiation therapy in the management of patients with advanced endometrial cancer. The proposed protocol design requires that chemotherapy be administered prior to radiation therapy in order to control distant metastatic disease before attempting to control for local-regional recurrences with radiation.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

- All patients with advanced endometrial adenocarcinoma, stage III A, B, C and Stage IV confined to the pelvis, and recurrent disease limited to the pelvis.

Surgical stage III and limited stage IV disease, including those patients with positive adnexa, tumor invading the serosa, positive and/or para-aortic nodes, pelvic metastases, positive pelvic washings or vaginal involvement.

Histology must be adenocarcinoma, adenosquamous cell, squamous cell, clear cell or serous papillary carcinoma

Status post surgical resection, including a hysterectomy and bilateral salpingo-oophorectomy within the past 6 weeks (Pelvic lymph node and para-aortic lymph node sampling are optional)

Patients may be sub-optimally or optimally debulked (disease < 2 cm). Patients are eligible with measurable disease or evaluable disease. All positive para-aortic node patients must be further staged by chest CT scan. If chest CT scan is negative, patients are eligible.

Patients who have met the pre-entry criteria including following lab findings:

ANC > 1500, Platelet count > 100,000/mm3, Hemoglobin ≥ 8 mg/dl, Creatinine < 2.0 mg/dl.

Total Bilirubin must be within normal limits. (WNL)

AST or ALT and Alkaline Phosphatase must be within the range allowing for eligibility

Patients who have signed an approved informed consent.

GOG Performance Grade 0, 1, or 2.

Women ≥ 18 years of age

Exclusion Criteria:

- Patients with Stage IV or recurrent disease outside of the pelvis.

Patients who have had prior pelvic or abdominal radiation therapy.

Patients with concomitant malignancy other than non-melanoma skin cancer.

Patient with a prior malignancy who have been disease-free for < 5 years or who received prior chemotherapy or radiation therapy for that malignancy.

Patients with a history of serious co-morbid illness that would preclude protocol therapy.

Patients with an estimated survival of less than three months.

Patients with parenchymal liver metastases.

Patients who received prior chemotherapy excluding low-dose methotrexate for rheumatologic reasons.

Histology consistent with uterine sarcomas, carcinosarcoma or leiomyosarcoma.

Women with baseline peripheral neuropathy Grade ≥ 2.

Women with a history of severe hypersensitivity reaction to drugs formulated with polysorbate 80.

  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: NCT00285415

Locations
United States, South Carolina
Gynecologic Oncology Research & Development, LLC
Greenville, South Carolina, United States, 29601
United States, Virginia
Carilion GYN Oncology Associates
Roanoke, Virginia, United States, 24014
Sponsors and Collaborators
Carilion Clinic
Sanofi
Investigators
Principal Investigator: Dennis R Scribner, JR, MD
  More Information

No publications provided

Responsible Party: Carilion Clinic
ClinicalTrials.gov Identifier: NCT00285415     History of Changes
Other Study ID Numbers: EndoRT, WIRB PRO NUM: 20050247
Study First Received: January 31, 2006
Last Updated: October 24, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Carilion Clinic:
Advanced endometrial adenocarcinoma, stage III A, B, C

Additional relevant MeSH terms:
Adenocarcinoma
Uterine Neoplasms
Carcinoma
Genital Diseases, Female
Genital Neoplasms, Female
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Urogenital Neoplasms
Uterine Diseases
Carboplatin
Docetaxel
Antimitotic Agents
Antineoplastic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on November 25, 2014