Clinical trial NCT00004221: Combination Chemotherapy and Peripheral Stem Cell Transplantation in Treating Patients With Stage III Ovarian Cancer
Official title: A Phase II Trial Using Multiple Cycles of High Dose Sequential Carboplatin, Paclitaxel and Topotecan With Peripheral Blood Stem Cell (PBSC) Support as Initial Chemotherapy in Patients With Optimally Debulked Stage III Ovarian and Primary Peritoneal Carcinoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Malignant Ovarian Mixed Epithelial Tumor
Ovarian Clear Cell Cystadenocarcinoma
Ovarian Endometrioid Adenocarcinoma
Ovarian Mucinous Cystadenocarcinoma
Ovarian Serous Cystadenocarcinoma
Primary Peritoneal Carcinoma
Stage III Ovarian Cancer
Undifferentiated Ovarian Carcinoma
Lead sponsor: GOG Foundation
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-08-25
Enrollment: 12
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Phase II trial to study the effectiveness of combination chemotherapy and peripheral stem cell transplantation in treating patients who have undergone surgery for stage III ovarian cancer. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells.

Detailed description: OBJECTIVES:

I. Determine the safety and feasibility of multiple courses of high dose carboplatin, paclitaxel, and topotecan as initial chemotherapy combined with autologous peripheral blood stem cell transplantation in patients with optimally debulked stage III ovarian or primary peritoneal carcinoma.

II. Determine the pathological complete response rate, disease free survival, and overall survival in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Mobilization and harvest: Within 8 weeks of surgical debulking, patients receive cyclophosphamide IV over 1 hour, followed 4 hours later by paclitaxel IV over 24 hours. Patients receive filgrastim (G-CSF) subcutaneously (SQ) daily beginning 24 hours after completion of paclitaxel infusion and continuing until blood counts recover and autologous peripheral blood stem cells (PBSC) are harvested and selected for CD34+ cells.

High dose chemotherapy and transplantation (3 weeks after PBSC harvest): Patients receive paclitaxel IV over 24 hours beginning on day 1, immediately followed by carboplatin IV over 2 hours, immediately followed by topotecan IV over 24 hours. Patients receive G-CSF sub-cutaneously (SQ) daily beginning 24 hours after completion of topotecan infusion and continuing until blood counts have recovered for 2 days. One quarter of the PBSC are reinfused beginning 2 days after completion of topotecan infusion. Treatment repeats every 4 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Patients with radiographic and biochemical complete response undergo laparoscopy as second look surgery within 8 weeks of the last course of chemotherapy. If no evidence of disease is found during laparoscopy, then exploratory laparotomy must also be performed.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter or at time of recurrence until death.

Eligibility criteria: Inclusion Criteria:

* Histologically proven optimally debulked stage III ovarian or primary peritoneal carcinoma

  * Any of the following subtypes:

    * Serous adenocarcinoma
    * Mucinous adenocarcinoma
    * Clear cell carcinoma
    * Transitional cell carcinoma
    * Endometrioid adenocarcinoma
    * Undifferentiated adenocarcinoma
    * Mixed epithelial adenocarcinoma
    * Adenocarcinoma, not otherwise specified
* No ovarian carcinoma of low malignant potential (borderline)
* Concurrent superficial endometrial or cervical carcinoma allowed if ovarian carcinoma more life threatening or limiting
* Must have undergone appropriate primary surgical staging and debulking for ovarian carcinoma and have less than 1 cm of residual disease

  * No more than 8 weeks since prior surgical debulking
* Must have Hickman catheter in place or be eligible for placement
* No CNS involvement
* Performance status - GOG 0 or 1
* Absolute neutrophil count at least 1,500/mm\^3
* Platelet count at least 100,000/mm\^3
* Bilirubin no greater than 1.5 mg/dL
* SGOT or SGPT no greater than 2 times upper limit of normal
* No active hepatitis
* Creatinine no greater than 1.5 mg/dL
* Creatinine clearance at least 60 mL/min
* No renal failure
* Curatively treated ureteral obstruction allowed if above creatinine measurements met
* No congestive heart failure
* No myocardial infarction within the past 6 months
* No significant arrhythmias requiring medication
* No poorly controlled systolic or diastolic hypertension (diastolic blood pressure consistently greater than 100 mm Hg)
* No significant nonneoplastic pulmonary disease
* No other malignancy within the past 5 years except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
* HIV negative
* No other severe medical or psychiatric illness including, but not limited to the following:

  * Acute infection
  * Active peptic ulcer disease
  * Uncontrolled diabetes mellitus
  * Prior hospitalization for psychiatric illness, including severe depression or psychosis
  * Concurrent alcohol or drug abuse
* No prior chemotherapy for this malignancy
* No radiotherapy to greater than 25% of bone marrow
* See Disease Characteristics

Primary outcomes:
measure: Complete response defined as complete disappearance of all measurable and evaluable tumor documented at second-look surgery
timeFrame: Up to 11 years
measure: Indication of excessive toxicity defined as hospitalization > 14 days per course, delay of day 1 therapy > 14 days, or grade 3 (irreversible) or grade 4 vital organ toxicity (non-hematologic)
timeFrame: Up to 11 years
Secondary outcomes:
measure: Overall survival
timeFrame: Up to 11 years
measure: PFS
timeFrame: Up to 11 years
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Gynecologic Oncology Group
state: Pennsylvania
Study officials:
affiliation: Gynecologic Oncology Group
name: Russell Schilder
role: PRINCIPAL_INVESTIGATOR
References: