Trial of Radiation Therapy "Sandwiched" Between Chemotherapy to Treat Uterine Carcinosarcoma (MMMT)

This study is currently recruiting participants.
Verified June 2011 by Montefiore Medical Center
Sponsor:
Information provided by:
Montefiore Medical Center
ClinicalTrials.gov Identifier:
NCT01367301
First received: June 3, 2011
Last updated: June 23, 2011
Last verified: June 2011
  Purpose

The purpose of this study is to determine whether radiation therapy "sandwiched" between paclitaxel/carboplatin chemotherapy is effective in the treatment of uterine carcinosarcoma,and particularly whether this treatment will lessen the chance of the cancer returning in the pelvis or elsewhere in the body.


Condition Intervention Phase
Uterine Carcinosarcoma
Drug: Paclitaxel, Carboplatin and Radiation
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 Trial of Radiation Therapy "Sandwiched" Between Paclitaxel and Carboplatin in Patients With Uterine Carcinosarcoma

Resource links provided by NLM:


Further study details as provided by Montefiore Medical Center:

Primary Outcome Measures:
  • Recurrence-Free Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Recurrence-free survival is defined as date of entry to date of reappearance of disease. Site(s) and date of relapse will be recorded. Recurrent disease will be defined as pelvic or distant. Pelvic sites will be specified as vaginal or other, and distant sites will be specified as to their anatomic location. Relapse should be confirmed by histologic or cytologic evaluation when possible.


Secondary Outcome Measures:
  • Toxicity [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    Toxicities will be graded according to the NCI Common Toxicity Criteria (version 4). Myelosuppressive toxicity will be reported as the lowest observed white blood and platelet counts. Anemia and red blood cell transfusions will be noted. Gastrointestinal toxicities will be reported and hospitalizations for nausea,vomiting and diarrhea will be documented. Patients will be followed for potential long-term toxicities with complete histories and physical examinations. Any patient who receives at least one course of therapy and has follow-up information will be included for observation of toxicity.


Estimated Enrollment: 18
Study Start Date: May 2011
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Paclitaxel, Carboplatin and Radiation

    Weeks 1-9 Paclitaxel 175mg/m2/3 hour & Carboplatin (AUC=6.0) Repeat q 21 days x 3 cycles

    Weeks 8-13 Pelvic and Para-Aortic Radiation 6MV Photon Beam Energy 1.8 Gy Dose/Fx Total Dose 45Gy

    Weeks 14, 15, 16 High Dose Radiation (HDR) x3, or IMRT where appropriate Nucleotron Microselection Afterloading Technique 5 Gy to 0.5cm Depth from the Vaginal Cylinder Surface Total Dose 15 Gy

    Weeks 14-22 Paclitaxel 175mg/m2/3 hour & Carboplatin (AUC=5.0) Repeat q 21 days x 3 cycles

Detailed Description:

Uterine carcinosarcomas represent approximately 4% of primary uterine malignancies. However, our rates in the Bronx are about double the national rate likely due to a number of factors including the referral patterns and the ethnic and racial diversity of the community the investigator serve at Montefiore Medical Center. Carcinosarcoma is an aggressive uterine tumor with a poor prognosis and a recurrence rate of 53%. Sites of failure include pelvic and extrapelvic with most patients developing extrapelvic disease. Pelvic radiation decreases the risk of pelvic recurrence, but has not been shown to improve overall survival secondary to extrapelvic recurrences and the hematogenous route of metastasis. Use of radiotherapy alone does not control extrapelvic recurrences. Combination chemotherapy has been shown to provide an improvement in response rate but with increased toxicity. The investigators have had considerable experience here at Montefiore combining sequenced radiation therapy sandwiched with chemotherapy before and after radiation therapy for both carcinosarcoma and uterine papillary serous carcinoma. In our most recent carcinosarcoma trial, 27 patients with surgical stage 1-4 uterine carcinosarcoma, without evidence of gross disease, were treated with adjuvant ifosfamide/cisplatin or ifosfamide for three cycles, then received pelvic external beam radiotherapy and brachytherapy followed by three more cycles of ifosfamide/cisplatin or ifosfamide. The two year disease free survival for stage I patients was 18.75 months and for stages II-IV was 15.81 months. Similar to a GOG trial in the recurrent setting, in our adjuvant trial, toxicity was increased in patients who received ifosfamide with cisplatin without added efficacy. Thus, in the last cohort of this trial, the investigators dropped the cisplatin from the regimen because it was adding toxicity without benefit. In our uterine papillary serous carcinoma "sandwich" trial, 30 patients with surgical stages I-IV, without evidence of gross residual disease received adjuvant paclitaxel/platinum for three cycles, followed by external beam pelvic radiotherapy and brachytherapy, and then three more cycles of paclitaxel/platinum. The three year disease free survival for stage I/II patients was 69% and for stage III/IV patients was 54%. 29 out of the 30 patients completed the protocol with grade 3/4 neutropenia occurring in 42% of cycles. 6 out of 177 cycles were delayed 1 week for neutropenia. Both in-house trials of sequenced chemotherapy and radiation therapy resulted in higher than expected survival in the adjuvant setting. Multiple studies have demonstrated a response of carcinosarcoma to carboplatin and paclitaxel as well as the role of adjuvant radiotherapy in improvement in local control. Due to the recent reports of efficacy of paclitaxel and carboplatin in recurrent carcinosarcoma, this pilot protocol is designed to determine the toxicity and clinical benefit of radiation therapy "sandwiched" between three cycles of paclitaxel and carboplatin before and after radiation therapy.

  Eligibility

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

Inclusion Criteria:

  • Histologically documented uterine carcinosarcoma with no visible residual disease.
  • Surgical staging to include total abdominal hysterectomy, bilateral salpingo- oophorectomy, peritoneal washings, and lymph node samplings.
  • Patients must be entered no more than 12 weeks post operatively.
  • Age > 18 years.
  • ECOG performance status of < 2.
  • Written voluntary informed consent.

Exclusion Criteria:

  • Patient has impairment of hepatic, renal or hematologic function as defined by the following baseline laboratory values:
  • Serum SGOT and /or 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/mm3
  • Absolute neutrophil count (ANC) < 1500/mm3
  • Hemoglobin < 8.0 g/dl (the patient may be transfused prior to study entry)
  • Patient has severe or uncontrolled concurrent medical disease (eg. 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01367301

Contacts
Contact: Loraine Centrilla, RN (718) 405-8082 LCENTRIL@montefiore.org

Locations
United States, New York
Montefiore Medical Center Recruiting
Bronx, New York, United States, 10461
Sub-Investigator: Mark H Einstein, MD, MS         
Sub-Investigator: Gary L Goldberg, MD         
Sub-Investigator: Harriet Smith, MD         
Sub-Investigator: Dennis, Yi-Shin Kuo, MD         
Sub-Investigator: Gloria S Huang, MD         
Sub-Investigator: David Smotkin, MD         
Sub-Investigator: Nicole Nevadunsky, MD         
Sub-Investigator: June Hou, MD         
Sub-Investigator: Shalom Kalnicki, MD         
Sub-Investigator: Keyur Mehta, MD         
Sub-Investigator: Madhur Garg, MD         
Sponsors and Collaborators
Montefiore Medical Center
Investigators
Principal Investigator: Merieme Klobocista, MD Montefiore Medical Center
  More Information

No publications provided

Responsible Party: Merieme Klobocista, MD/Principal Investigator, Montefiore Medical Center
ClinicalTrials.gov Identifier: NCT01367301     History of Changes
Other Study ID Numbers: 11-02-064
Study First Received: June 3, 2011
Last Updated: June 23, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by Montefiore Medical Center:
Uterine Carcinosarcoma
Radiation Therapy
Paclitaxel
Carboplatin

Additional relevant MeSH terms:
Uterine Diseases
Carcinosarcoma
Mixed Tumor, Mullerian
Uterine Neoplasms
Neoplasms, Complex and Mixed
Neoplasms by Histologic Type
Neoplasms
Sarcoma
Neoplasms, Connective and Soft Tissue
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Female
Carboplatin
Paclitaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on April 15, 2014