Clinical trial NCT00331422: Carboplatin, Paclitaxel, and Surgery in Treating Patients With Advanced Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cavity Cancer
Official title: A Phase II Study of Carboplatin and Paclitaxel as Neoadjuvant Chemotherapy Followed by Interval Cytoreduction in Women With Advanced Staged Epithelial Ovarian, Fallopian Tube and Primary Peritoneal Carcinoma for High-Risk Surgical Candidates or Patients Unlikely to be Optimally Surgically Cytoreduced
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Fallopian Tube Cancer
Ovarian Cancer
Peritoneal Cavity Cancer
Keywords: ovarian clear cell cystadenocarcinoma
ovarian endometrioid adenocarcinoma
ovarian mixed epithelial carcinoma
ovarian mucinous cystadenocarcinoma
ovarian serous cystadenocarcinoma
ovarian undifferentiated adenocarcinoma
stage III ovarian epithelial cancer
stage IV ovarian epithelial cancer
peritoneal cavity cancer
fallopian tube cancer
Brenner tumor
Lead sponsor: Masonic Cancer Center, University of Minnesota
Sponsor class: OTHER
First posted: 2006-05-31
Enrollment: 7
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or stopping them from dividing. Giving chemotherapy drugs before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

PURPOSE: This phase II trial is studying how well giving paclitaxel together with carboplatin before surgery works in treating patients with advanced ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cavity cancer.

Detailed description: OBJECTIVES:

Primary

* Determine whether at least 50% of patients with advanced ovarian epithelial, fallopian tube, or primary peritoneal cavity cancer are able to achieve optimal cytoreduction (to \< 1 centimeter of remaining disease) after neoadjuvant chemotherapy comprising paclitaxel and carboplatin.

Secondary

* Determine the frequency and severity of toxicity associated with this regimen in patients who are high-risk surgical candidates or in patients unlikely to achieve optimal surgical cytoreduction.
* Determine if extreme drug resistance assay profiles change after neoadjuvant chemotherapy.
* Determine how thrombospondin-1 (TSP-1), tumor protein 53 (p53), and tumor vessel density change after administration of neoadjuvant chemotherapy.
* Assess the quality of life of patients receiving neoadjuvant chemotherapy.
* Obtain estimates of tumor response after administration of neoadjuvant chemotherapy.
* Determine whether serum cancer antigen 125 (CA-125) at the time of cytoreduction is associated with the ability to optimally reduce the patients.

OUTLINE: This is an open-label study.

Patients receive paclitaxel intravenously (IV) over 3 hours and carboplatin IV over 30 minutes on day 1. Treatment repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. Within 4-6 weeks after the fourth course of chemotherapy, patients undergo interval cytoreductive surgery.

Patients who are unable to undergo surgery receive 2 additional courses of chemotherapy and are re-evaluated for surgery after the sixth course of chemotherapy.

Within 4 weeks after surgery, patients receive 2 additional courses of chemotherapy.

Quality of life is assessed periodically.

Tumor samples are obtained via laparoscopic or percutaneous biopsy prior to beginning chemotherapy and during interval cytoreduction. Tissue is examined by immunohistochemistry staining for p53, TSP-1, microvessel density (CD31), angiogenesis, membrane protein BCL-2, and multidrug resistant gene 1 (MDR-1). Gene array analysis and extreme drug resistant assays are also performed.

After completion of study treatment, patients are followed every 3 months for 2 years.

Eligibility criteria: Inclusion Criteria:

* Patients with histological diagnosis of epithelial ovarian, primary peritoneal, or fallopian tube carcinoma for which no previous treatment has been given.

Patients with the following histological epithelial cell types are eligible:

* Serous adenocarcinoma
* Mucinous adenocarcinoma
* Clear cell adenocarcinoma
* Transitional cell
* Adenocarcinoma not otherwise specified
* Endometrioid adenocarcinoma
* Undifferentiated carcinoma
* Mixed epithelial carcinoma
* Malignant Brenner's tumor

  * Measurable or non-measurable disease as defined by Solid Tumor Response Criteria (RECIST) within 4 weeks of study entry
  * High-risk surgical candidate
  * Gynecologic Oncology Group (GOG) performance status 0-3
  * Absolute neutrophil count ≥ 1,500/mm\^3
  * Platelet count ≥ 100,000/mm\^3
  * Creatinine ≤ 1.5 mg/dL
  * Alkaline phosphatase ≤ 3 times upper limit of normal (ULN)
  * Bilirubin ≤ 1.5 times ULN
  * Serum glutamic oxaloacetic transaminase (SGOT) ≤ 3 times ULN
  * Life expectancy ≥ 12 weeks

Exclusion Criteria:

* Pregnant or nursing
* Positive pregnancy test -(Fertile patients must use effective nonhormonal contraception during and for 3 months after completion of study treatment.)
* History of another neoplasm except for non-metastatic, non-melanoma skin cancers, carcinoma in situ of the cervix, or cancer cured by surgery \> 5 years prior to registration.
* Septicemia, severe infection, acute hepatitis, or severe gastrointestinal bleeding, defined as requiring blood transfusion or hospitalization at registration
* Unstable angina will not be eligible. Patients with evidence of abnormal cardiac conduction (e.g. bundle branch block, heart block) are eligible if their disease has been stable for the past six months.
* History of severe hypersensitivity or allergic reaction to study drugs, drugs formulated in Cremophor EL\^®, other platinol compounds, or mannitol

Primary outcomes:
measure: Number of Patients Who Underwent Optimal Cytoreduction After Chemotherapy
timeFrame: Week 18 (After 4 cycles of chemotherapy)
Secondary outcomes:
measure: Patients' Overall Tumor Response as Measured by Response Evaluation Criteria in Solid Tumors (RECIST)
timeFrame: Week 16 (4 weeks after 4th course)
measure: Clinical Response Based on Serum Cancer Antigen 125 (CA-125) Concentration
timeFrame: From Baseline to up to 12 weeks (4 courses of therapy)
measure: Change in Drug Resistance After Neoadjuvant Chemotherapy
timeFrame: Day 1 to Time to Surgery (Approximately Week 18)
measure: Change in Thrombospondin-1 (TSP-1), p53, and Tumor Vessel Density
timeFrame: Week 18 (At surgery)
measure: Quality of Life Score of Patients Receiving Neoadjuvant Chemotherapy
timeFrame: Day 1, Week 12 (after 4th course) , Week 16 (4 weeks after last treatment)
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: University of Minnesota Cancer Center
state: Minnesota
Study officials:
affiliation: Masonic Cancer Center, University of Minnesota
name: Melissa A. Geller, MD
role: STUDY_CHAIR
References: