S0009 Combination Chemo and Surgery in Stage III or Stage IV Ovarian Cancer

Ovarian Cancer Clinical Trial

— S0009  

Official title:

Phase II Evaluation Of Neoadjuvant Chemotherapy, Interval Debulking Followed By Intraperitoneal Chemotherapy In Women With Stage III And IV Epithelial Ovarian Cancer, Fallopian Tube Cancer Or Primary Peritoneal Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00008138
• Other study ID #: CDR0000068380
• Secondary ID: U10CA032102S0009
• Status: Completed
• Phase: Phase 2
• First received: January 6, 2001
• Last updated: December 8, 2015
• Start date: March 2001
• Est. completion date: November 2009

Study information

• Verified date: December 2015
• Source: Southwest Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug or combining chemotherapy with surgery may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy and surgery in treating patients who have stage III or stage IV ovarian epithelial cancer, primary peritoneal cancer, or fallopian tube cancer.

Description:

OBJECTIVES:

• Evaluate the overall survival and progression-free survival in patients with stage III or IV ovarian epithelial cancer, primary peritoneal cancer, or fallopian tube cancer treated with neoadjuvant paclitaxel and carboplatin followed by surgery and adjuvant paclitaxel and carboplatin.

• Estimate the percentage of these patients whose disease is successfully cytoreduced to less than 1 cm in diameter following neoadjuvant chemotherapy.

• Evaluate the toxicity of this regimen in these patients.

• Explore the relationship between tumor p53 expression, proliferation rate as measured by proliferating cell nuclear antigen and apoptotic rate, and human tumor cloning assay results at time of debulking surgery with progression-free survival and overall survival in these patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive neoadjuvant therapy comprising paclitaxel IV over 3 hours followed by carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Within 35 days of receiving the third course of chemotherapy, patients with at least a 50% reduction in CA 125 undergo debulking surgery. Within 35 days of undergoing surgery, patients with a tumor reduction to below 1 cm receive adjuvant therapy comprising paclitaxel IV over 3 hours followed by carboplatin intraperitoneally (IP) on day 1 and paclitaxel IP on day 8. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually for up to 5 years.

PROJECTED ACCRUAL: A total of 55 patients will be accrued for this study within 3 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 62
• Est. completion date: November 2009
• Est. primary completion date: September 2009
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 120 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed stage III or IV ovarian epithelial cancer, primary peritoneal cancer, or fallopian tube cancer

• Adenocarcinoma

• Large pelvic mass and/or bulky abdominal disease and/or malignant pleural effusion

• Pleural effusion only for stage IV (parenchymal, liver, lung, or other distant metastases not allowed)

• No borderline or low-malignant potential tumors

• Optimal cytoreduction clinically deemed unlikely

• CA 125 at least 70 units/mL

PATIENT CHARACTERISTICS:

Age:

• Not specified

Performance status:

• Zubrod 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Granulocyte count at least 1,500/mm^3

• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 2 times upper limit of normal (ULN)

• SGOT no greater than 2 times ULN

Renal:

• Creatinine clearance at least 50 mL/min

Cardiovascular:

• No congestive heart failure or cardiac arrhythmia

• No myocardial infarction or angina within past 6 months

Other:

• Not pregnant or nursing

• Fertile patients must use effective contraception

• No severe gastrointestinal symptoms (i.e., partial obstruction) and/or gastrointestinal bleeding

• No grade 2 or greater sensory neuropathy

• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or other adequately treated stage I or II cancer in complete remission

• No active or uncontrolled infection

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior immunotherapy for this cancer

Chemotherapy:

• No prior chemotherapy for this cancer

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior pelvic radiation for this cancer

Surgery:

• See Disease Characteristics

• Prior exploratory laparotomy allowed provided an aggressive tumor debulking procedure was not performed (e.g., bilateral salpingo-oophorectomy/total abdominal hysterectomy with omentectomy)

• Prior salpingo-oophorectomy and/or partial omentectomy allowed

Other:

• No other concurrent anti-cancer therapy

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Fallopian Tube Cancer
• Fallopian Tube Neoplasms
• Ovarian Cancer
• Ovarian Neoplasms
• Peritoneal Cavity Cancer
• Peritoneal Neoplasms

Intervention

Drug:
• carboplatin
pre-surgery - target AUC=6, Day 1 IV, q 21 days X 3 cycles post-surgery - target AUC=5, Day 1 IP, q 28 days X 6 cycles
• paclitaxel
pre-surgery - 175 mg/m2 IV Day 1, q 21 days X 3 cycles post-surgery - 175 mg/m2 IV Day 1, q 28 days X 6 cycles AND 60 mg/m2 IP Day 8, q 28 days X 6 cycles

Procedure:
• debulking surgery
exploratory laparotomy, interval cytoreduction (to < 1 cm residual)

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Southwest Oncology Group	National Cancer Institute (NCI)

References & Publications (1)

Tiersten AD, Liu PY, Smith HO, Wilczynski SP, Robinson WR 3rd, Markman M, Alberts DS. Phase II evaluation of neoadjuvant chemotherapy and debulking followed by intraperitoneal chemotherapy in women with stage III and IV epithelial ovarian, fallopian tube — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival	Overall survival was defined as the time from the date of registration until the date of death due to any cause. Patients last known to be alive were censored at the date of last contact. Patients were followed every 3 months for the first year, every 6 months for years 2 and 3, and then annually for years 4 and 5.	assessed every 3 months for 1st year, then every 6 months for 2 years, then annually for years 4 and 5	No
Primary	Progression-Free Survival	Progression was defined as a CA-125 value that is both twice the nadir since registration and greater than 70 units/ml, and is confirmed by a second determination at least 7 days apart, or appearance of any new lesion/site. Symptomatic deterioration was defined as a global deterioration of health status requiring removal from protocol treatment. Progression-Free Survival was defined as the time from the date of registration to the date of progression, symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression-free were censored at last contact date.	Monthly during protocol treatment, then every 3 months up to the end of Year 1, then every 6 months for the next two years, then annually up to Year 5.	No