Intraperitoneal Paclitaxel, Doxorubicin Hydrochloride, and Cisplatin in Treating Patients With Stage III-IV Endometrial Cancer

Sponsor

Gynecologic Oncology Group (Other)

Overall Status

Completed

CT.gov ID

NCT00575952

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Arm

101.9

Actual Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This phase I trial studies the side effects and best dose of intraperitoneal paclitaxel when given together with doxorubicin hydrochloride and cisplatin in treating patients with stage III-IV endometrial cancer. Drugs used in chemotherapy, such as paclitaxel, doxorubicin hydrochloride, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) and giving them in different ways may kill more tumor cells.

Condition or Disease	Intervention/Treatment	Phase
Endometrial Adenosquamous Carcinoma Endometrial Clear Cell Adenocarcinoma Endometrial Mixed Adenocarcinoma Endometrial Serous Adenocarcinoma Endometrial Squamous Cell Carcinoma Endometrial Undifferentiated Carcinoma Recurrent Uterine Corpus Carcinoma Stage IIIA Uterine Corpus Cancer Stage IIIC Uterine Corpus Cancer Stage IVA Uterine Corpus Cancer Stage IVB Uterine Corpus Cancer	Drug: Cisplatin Drug: Doxorubicin Hydrochloride Biological: Filgrastim Drug: Paclitaxel Biological: Pegfilgrastim	Phase 1

Detailed Description

PRIMARY OBJECTIVES:

To determine the maximum tolerated dose of intraperitoneal (IP) paclitaxel when given concurrently with fixed dose intravenous (IV) doxorubicin (doxorubicin hydrochloride) and IV cisplatin.
To determine the maximum tolerated dose of IP paclitaxel when given concurrently with fixed dose IV doxorubicin hydrochloride and IP cisplatin.
To determine the feasibility of an IV/IP based doxorubicin hydrochloride, paclitaxel, and cisplatin chemotherapy regimen in patients with advanced endometrial cancer.

OUTLINE: This is a dose-escalation study of paclitaxel.

Patients receive doxorubicin hydrochloride IV over 30 minutes followed by cisplatin IV over 1 hour on day 1, paclitaxel IV over 3 hours on day 2, and filgrastim subcutaneously (SC) on days 3-12 or pegfilgrastim SC on day 3. Treatment repeats every 21 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.

Patients then receive doxorubicin hydrochloride IV and cisplatin IV or IP on day 1, and paclitaxel IP on days 1 or 8. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 1 year.

Study Design

Study Type:

Interventional

Actual Enrollment :

27 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I Study of IV Doxorubicin Plus Intraperitoneal (IP) Paclitaxel and IV or IP Cisplatin in Endometrial Cancer Patients at High Risk for Peritoneal Failure

Actual Study Start Date :

Jan 17, 2008

Actual Primary Completion Date :

Jul 16, 2016

Actual Study Completion Date :

Jul 16, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (doxorubicin hydrochloride, cisplatin, paclitaxel) Patients receive doxorubicin hydrochloride IV over 30 minutes followed by cisplatin IV over 1 hour on day 1, paclitaxel IV over 3 hours on day 2, and filgrastim SC on days 3-12 or pegfilgrastim SC on day 3. Treatment repeats every 21 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients then receive doxorubicin hydrochloride IV and cisplatin IV or IP on day 1, and paclitaxel IP on days 1 or 8. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.	Drug: Cisplatin Given IV or IP Drug: Doxorubicin Hydrochloride Given IV Biological: Filgrastim Given SC Drug: Paclitaxel Given IV or IP Biological: Pegfilgrastim Given SC

Arm

Intervention/Treatment

Experimental: Treatment (doxorubicin hydrochloride, cisplatin, paclitaxel)

Patients receive doxorubicin hydrochloride IV over 30 minutes followed by cisplatin IV over 1 hour on day 1, paclitaxel IV over 3 hours on day 2, and filgrastim SC on days 3-12 or pegfilgrastim SC on day 3. Treatment repeats every 21 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients then receive doxorubicin hydrochloride IV and cisplatin IV or IP on day 1, and paclitaxel IP on days 1 or 8. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

Drug: Cisplatin

Given IV or IP

Drug: Doxorubicin Hydrochloride

Given IV

Biological: Filgrastim

Given SC

Drug: Paclitaxel

Given IV or IP

Biological: Pegfilgrastim

Given SC

Outcome Measures

Primary Outcome Measures

Incidence of observed DLTs, defined as grade 3-4 hematologic or non-hematologic toxicity graded using CTCAE v3.0 [18 weeks]
Maximum tolerated dose (MTD) of IP paclitaxel with fixed dose IV doxorubicin hydrochloride and IV cisplatin, determined according to dose-limiting toxicities (DLTs) graded using CTCAE v3.0 [12 weeks]
MTD of IP paclitaxel with fixed dose IV doxorubicin hydrochloride and IP cisplatin, determined according to DLTs graded using CTCAE v3.0 [12 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients with stage IIIA, or stage IIIC with positive cytologic washings/ascites, adnexal spread, or serosal involvement, or stage IV (by virtue of intraperitoneal disease spread) histologically confirmed endometrial cancer (endometrioid, serous, clear cell, squamous/adenosquamous, undifferentiated, or mixed histologies)
Patients must be optimally cytoreduced with less than or equal to 2 cm residual disease
Absolute neutrophil count (ANC) greater than or equal to 1,500/mm^3, equivalent to Common Toxicity Criteria (Common Terminology Criteria for Adverse Events [CTCAE] version 3.0 [v3.0]) grade 1
Platelets greater than or equal to 100,000/mm^3 (CTCAE v3.0 grade 0-1)
Hemoglobin greater than or equal to 10 g/dl (CTCAE v3.0 grade 1)
Creatinine less than or equal to 2 mg/% or 24 hour creatinine clearance > 50 ml/min
Bilirubin less than or equal to 1.5 x upper limit of normal (ULN) (CTCAE v3.0 grade 1)
Serum glutamic oxaloacetic transaminase (SGOT) less than or equal to 2.5 x ULN (CTCAE v3.0 grade 1)
Neuropathy (sensory and motor) less than or equal to CTCAE v3.0 grade 1
Patients must have normal ejection fraction
Patients must be enrolled within 8 weeks of surgery
Patients who have met the pre-entry requirements
Patients must have signed an approved informed consent and authorization permitting release of personal health information
Patients must have a Gynecologic Oncology Group (GOG) performance status of 0, 1, or 2

Exclusion Criteria:

Metastatic disease involving lung or liver parenchyma, bone or inguinal or scalene lymph nodes
Patients with GOG performance grade of 3 or 4
Patients with concomitant medical illness such as serious uncontrolled infection, uncontrolled angina, or serious peripheral neuropathy, which in the opinion of the treating physician, makes the protocol prescribed treatments hazardous to the patient
Patients with 3rd degree or complete heart block are not eligible unless a pacemaker is in place; patients who are on medications which alter cardiac conduction (digitalis, beta blockers, calcium channel blockers) or who have other cardiac conduction abnormalities may be placed on study at the discretion of the investigator
Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer, are excluded if there is any evidence of other malignancy being present within the last five years; patients are also excluded if their previous cancer treatment contraindicates this protocol therapy
Patients who have received prior radiation or chemotherapy for the cancer being treated in this study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hartford Hospital	Hartford	Connecticut	United States	06102
2	The Hospital of Central Connecticut	New Britain	Connecticut	United States	06050
3	University of Chicago Comprehensive Cancer Center	Chicago	Illinois	United States	60637
4	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa	United States	52242
5	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
6	Cooper Hospital University Medical Center	Camden	New Jersey	United States	08103
7	Case Western Reserve University	Cleveland	Ohio	United States	44106
8	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
9	Women and Infants Hospital	Providence	Rhode Island	United States	02905