Combination Chemotherapy and Peripheral Stem Cell Transplantation in Treating Patients With Stage III Ovarian Cancer

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

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.

Study Overview

• Status: Terminated
• Conditions: Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Serous Cystadenocarcinoma; Primary Peritoneal Carcinoma; Malignant Ovarian Mixed Epithelial Tumor; Ovarian Mucinous Cystadenocarcinoma; Undifferentiated Ovarian Carcinoma; Stage III Ovarian Cancer
• Intervention / Treatment: Drug: Carboplatin; Drug: Paclitaxel; Drug: Cyclophosphamide; Drug: Topotecan Hydrochloride; Biological: Filgrastim; Procedure: Peripheral Blood Stem Cell Transplantation

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.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19103
      • Gynecologic Oncology Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (Combination chemotherapy, PBSC); See detailed description.

Drug: Carboplatin; Given IV; Other Names: Blastocarb; Carboplat; Carboplatin Hexal; Carboplatino; Carbosin; Carbosol; Carbotec; CBDCA; Displata; Ercar; JM-8; Nealorin; Novoplatinum; Paraplatin; Paraplatin AQ; Paraplatine; Platinwas; Ribocarbo; Paraplat; Drug: Paclitaxel; Given IV; Other Names: Taxol; Anzatax; Asotax; Bristaxol; Praxel; Taxol Konzentrat; Drug: Cyclophosphamide; Given IV; Other Names: Cytoxan; CTX; (-)-Cyclophosphamide; 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate; Carloxan; Ciclofosfamida; Ciclofosfamide; Cicloxal; Clafen; Claphene; CP monohydrate; CYCLO-cell; Cycloblastin; Cycloblastine; Cyclophospham; Cyclophosphamid monohydrate; Cyclophosphamidum; Cyclophosphan; Cyclophosphane; Cyclophosphanum; Cyclostin; Cyclostine; Cytophosphan; Cytophosphane; Fosfaseron; Genoxal; Genuxal; Ledoxina; Mitoxan; Neosar; Revimmune; Syklofosfamid; WR- 138719; Drug: Topotecan Hydrochloride; Given IV; Other Names: Hycamtin; Hycamptamine; SKF S-104864-A; Topotecan HCl; topotecan hydrochloride (oral); Biological: Filgrastim; Given SQ; Other Names: G-CSF; r-metHuG-CSF; Neupogen; Recombinant Methionyl Human Granulocyte Colony Stimulating Factor; rG-CSF; Tevagrastim; Filgrastim XM02; Tbo-filgrastim; Procedure: Peripheral Blood Stem Cell Transplantation; Undergo autologous peripheral blood stem cell transplantation; Other Names: PBPC transplantation; Peripheral Blood Progenitor Cell Transplantation; Peripheral Stem Cell Support; Peripheral Stem Cell Transplantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Complete response defined as complete disappearance of all measurable and evaluable tumor documented at second-look surgery	Up to 11 years
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)	Up to 11 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival	Up to 11 years
PFS	Up to 11 years

Collaborators and Investigators

• Sponsor: Gynecologic Oncology Group
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: November 1, 1999
• Primary Completion (Actual): February 6, 2002

Study Registration Dates

• First Submitted: January 28, 2000
• First Submitted That Met QC Criteria: August 22, 2003
• First Posted (Estimate): August 25, 2003

Study Record Updates

• Last Update Posted (Actual): August 9, 2017
• Last Update Submitted That Met QC Criteria: August 8, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Uterine Neoplasms; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Neoplasms, Cystic, Mucinous, and Serous; Endometrial Neoplasms; Carcinoma; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Cystadenocarcinoma, Serous; Carcinoma, Endometrioid; Cystadenocarcinoma; Cystadenocarcinoma, Mucinous; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase Inhibitors; Adjuvants, Immunologic; Topoisomerase I Inhibitors; Cyclophosphamide; Carboplatin; Paclitaxel; Lenograstim; Albumin-Bound Paclitaxel; Topotecan
• Other Study ID Numbers: GOG-9903 (Other Identifier: CTEP); U10CA027469 (U.S. NIH Grant/Contract); NCI-2012-02312 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); CDR0000067462