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

NCT ID: NCT00231868

Last Updated: 2020-08-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 81 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-12-31
• Study Completion Date: 2011-07-31

Brief Summary

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.

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.

Conditions

Uterine Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

A

Drug:Carboplatin and Paclitaxel and Radiation: Pelvic Radiation Therapy

Group Type: EXPERIMENTAL

Carboplatin and Paclitaxel and Pelvic Radiation Therapy

Intervention Type: DRUG

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

Carboplatin and Paclitaxel and Pelvic Radiation Therapy

Intervention Type: PROCEDURE

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

Carboplatin and Paclitaxel and Radiation Therapy

Intervention Type: DRUG

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

Interventions

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

Intervention Type: 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

Intervention Type: PROCEDURE

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

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Montefiore Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Dennis Yi-Shin Kuo

Attending

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mark H Einstein, M.D., M.S.

Role: PRINCIPAL_INVESTIGATOR

Montefiore Medical Center and Albert Einstein College of Medicine

Locations

Montefiore Medical Center

The Bronx, New York, United States

Countries

United States

References

Einstein MH, Frimer M, Kuo DY, Reimers LL, Mehta K, Mutyala S, Huang GS, Hou JY, Goldberg GL. Phase II trial of adjuvant pelvic radiation "sandwiched" between combination paclitaxel and carboplatin in women with uterine papillary serous carcinoma. Gynecol Oncol. 2012 Jan;124(1):21-5. doi: 10.1016/j.ygyno.2011.10.007. Epub 2011 Oct 27.

Reference Type: RESULT

PMID: 22035806 (View on PubMed)

Other Identifiers

01-09-227

Identifier Type: -

Identifier Source: org_study_id