Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

A Study of Radiation Therapy and Paclitaxel and Carboplatin in Patients With Uterine Papillary Serous Carcinoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Mark H. Einstein, Montefiore Medical Center
ClinicalTrials.gov Identifier:
NCT00231868
First received: October 3, 2005
Last updated: April 22, 2012
Last verified: April 2012
  Purpose

Combination chemo/radiotherapy trials in advanced/recurrent endometrial cancer are ongoing. The optimal radiation modality, chemotherapeutic agents, and sequence of these regimens for the treatment of UPSC are yet to be established. A retrospective review of 16 patients treated at our institution with the sequential use of radiation "sandwiched" between paclitaxel/platinum chemotherapy found only one patient to have recurred at 16 months with a median follow-up of 15 months (range 6-33 months). The regimen was well tolerated. Eight of the sixteen patients (50%) developed grade 3 neutropenia following cycle 4 of chemotherapy, two of which required a 1 week treatment delay. There were no cases of grade 3 or 4 thrombocytopenia noted. There was no febrile neutropenia and no hospital admissions for toxicity. There were no observed grade 3 or 4 non-hematologic toxicities. With the median follow up of 15 months, we have not observed late toxicities.

Given these favorable preliminary findings, supported by recently published data documenting efficacy of the "sandwich" multimodality technique in other difficult uterine malignancies (malignant mixed mullerian tumors), we propose to study this combination of chemotherapy and radiation prospectively. Our aim is to better evaluate patterns of recurrence and possible benefits in progression-free and overall survival.


Condition Intervention Phase
Uterine Cancer
Drug: Carboplatin and Paclitaxel and Pelvic Radiation Therapy
Procedure: Carboplatin and Paclitaxel and Pelvic Radiation Therapy
Drug: Carboplatin and Paclitaxel and Radiation Therapy
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
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 Uterine Papillary Serous Carcinoma

Resource links provided by NLM:


Further study details as provided by Montefiore Medical Center:

Primary Outcome Measures:
  • To evaluate the toxicity and tolerability of pelvic radiation "sandwiched" between cycles of paclitaxel/carboplatin chemotherapy in patients with UPSC [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To define patterns of recurrence, and one year recurrence-free survival in patients with UPSC treated with "sandwich" therapy: [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To correlate surrogate endpoint biomarkers with progression-free survival and prognosis. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Enrollment: 81
Study Start Date: December 2001
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
Drug:Carboplatin and Paclitaxel and Radiation: Pelvic Radiation Therapy
Drug: Carboplatin and Paclitaxel and Pelvic Radiation Therapy
Paclitaxel 175 mg/m2/3 hour & Carboplatin (AUC=6.5) Repeat q 21 days x 3 cycles followed by RT followed by Paclitaxel 175 mg/m2/3 hour & Carboplatin (AUC=5.0)Repeat q 21 days x 3 cycles
Procedure: Carboplatin and Paclitaxel and Pelvic Radiation Therapy
Paclitaxel 175 mg/m2/3 hour & Carboplatin (AUC=6.5) Repeat q 21 days x 3 cycles followed by RT followed by Paclitaxel 175 mg/m2/3 hour & Carboplatin (AUC=5.0)Repeat q 21 days x 3 cycles
Drug: Carboplatin and Paclitaxel and Radiation Therapy
Paclitaxel 175 mg/m2/3 hour & Carboplatin (AUC=6.5) Repeat q 21 days x 3 cycles followed by RT followed by Paclitaxel 175 mg/m2/3 hour & Carboplatin (AUC=5.0)Repeat q 21 days x 3 cycles

Detailed Description:

Uterine papillary serous carcinoma (UPSC) is an uncommon, but aggressive variant of endometrial carcinoma that has a high recurrence rate and poor response to therapy. It has a propensity to metastasize throughout the abdomen, similar to serous carcinoma of the ovary. In fact, many patients with disease apparently confined to the uterus have microscopic intra-abdominal spread at the time of diagnosis. Recurrences are common both in the pelvis as well as in the upper abdomen.

After staging and debulking of gross disease, adjuvant radiation therapy is recommended to treat patients with endometrial carcinoma at high risk for recurrent disease. High-risk features include histologic cell type, grade, depth of myometrial invasion, cervical extension, lymph-vascular invasion, adnexal involvement, intraperitoneal spread, positive peritoneal cytology, and positive lymph nodes. Pelvic radiation can limit local recurrences to less than 6.5%. However, approximately 25-30% of patients with high-risk features who receive radiation recur with distant metastases. Even patients treated with whole abdominal irradiation are at risk for extra-abdominal recurrences with progression-free intervals of 7 to 8 months.

Adjuvant chemotherapeutic regimens have been studied in high-risk endometrial cancers, but none have demonstrated a survival advantage. Doxorubicin, in combination with platinum, has a reported 42% response rate, but a high toxicity profile. Paclitaxel has an overall response rate of 36% in patients with advanced and recurrent endometrial cancer. Platinum-based chemotherapies have a 28-42% response rate.

Retrospective studies in patients with UPSC have demonstrated response rates of up to 35% in patients with multiagent chemotherapy. In one study, a median progression-free interval of 30 months was observed in patients treated with paclitaxel and platinum in the adjuvant and recurrent settings. Based on these findings and the similarities and clinical success of paclitaxel/platinum therapy in patients with ovarian serous carcinoma, this combination warrants further investigation in a prospective manner in patients with UPSC.

Combination chemo/radiotherapy trials in advanced/recurrent endometrial cancer are ongoing. The optimal radiation modality, chemotherapeutic agents, and sequence of these regimens for the treatment of UPSC are yet to be established. A retrospective review of 16 patients treated at our institution with the sequential use of radiation "sandwiched" between paclitaxel/platinum chemotherapy found only one patient to have recurred at 16 months with a median follow-up of 15 months (range 6-33 months). The regimen was well tolerated. Eight of the sixteen patients (50%) developed grade 3 neutropenia following cycle 4 of chemotherapy, two of which required a 1 week treatment delay. There were no cases of grade 3 or 4 thrombocytopenia noted. There was no febrile neutropenia and no hospital admissions for toxicity. There were no observed grade 3 or 4 non-hematologic toxicities. With the median follow up of 15 months, we have not observed late toxicities.

Given these favorable preliminary findings, supported by recently published data documenting efficacy of the "sandwich" multimodality technique in other difficult uterine malignancies (malignant mixed mullerian tumors), we propose to study this combination of chemotherapy and radiation prospectively. Our aim is to better evaluate patterns of recurrence and possible benefits in progression-free and overall survival.

Surrogate endpoint biomarkers such as ER/PR, HER2/Neu and p53 will be correlated with prognosis. In addition, fresh frozen tissue will be banked for future cDNA microarray analyses of UPSC tumors.

  Eligibility

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

Inclusion Criteria:

  1. Histologically documented uterine papillary serous carcinoma (UPSC) with no visible residual disease.
  2. Surgical staging to include total abdominal hysterectomy, bilateral salpingo-oophorectomy, peritoneal washings, and lymph node samplings.
  3. Age > 18 years.
  4. ECOG performance status of < 2.
  5. Written voluntary informed consent.

Exclusion Criteria:

  1. Patient has impairment of hepatic, renal or hematologic function as defined by the following baseline laboratory values:

    1. Serum SGOT and /or SGPT > 2.5 times the institutional upper limit of normal
    2. Total serum bilirubin > 1.5 mg/dl
    3. History of chronic or active hepatitis
    4. Serum creatinine > 2.0 mg/dl
    5. Platelets < 100,000/mm3
    6. Absolute neutrophil count (ANC) < 1500/mm3
    7. Hemoglobin < 8.0 g/dl (the patient may be transfused prior to study entry)
  2. Patient has severe or uncontrolled concurrent medical disease (eg. uncontrolled diabetes, unstable angina, myocardial infarction within 6 months, congestive heart failure, etc.)
  3. Patient has been treated with myelosuppressive chemotherapy within three weeks prior to study entry.
  4. Patient with any prior chemotherapy or radiotherapy for pelvic malignancy.
  5. 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
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: NCT00231868

Locations
United States, New York
Montefiore Medical Center
Bronx, New York, United States, 10461
Sponsors and Collaborators
Montefiore Medical Center
Investigators
Principal Investigator: Mark H Einstein, M.D., M.S. Montefiore Medical Center and Albert Einstein College of Medicine
  More Information

Publications:
Responsible Party: Mark H. Einstein, Director, Clinical Research for Women's Health, Montefiore Medical Center
ClinicalTrials.gov Identifier: NCT00231868     History of Changes
Other Study ID Numbers: MMC-01-09-227
Study First Received: October 3, 2005
Last Updated: April 22, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Montefiore Medical Center:
Uterine Papillary Serous Carcinoma
UPSC
Radiation Therapy
Chemotherapy

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

ClinicalTrials.gov processed this record on November 20, 2014