Fallopian Tube Cancer, Ovarian Cancer, Peritoneal Cavity Cancer
Conditions
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
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.
Interventions
DRUGcarboplatin
Carboplatin dose (milligrams (mg)) - Target Area Under the Curve (AUC) 6 x (Glomerular Filtration Rate+25) - Calvert Formula, given intravenously (IV) for 30 minutes.
DRUGpaclitaxel
Paclitaxel dose = 175 milligrams per meter squared (mg/m2) over 3 hours.
PROCEDUREcytoreductive surgery
Surgery - tumor specimen collected for extreme drug resistant assay (EDR) and A1 assays for analysis
Sponsors
Masonic Cancer Center, University of Minnesota
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Who Underwent Optimal Cytoreduction After Chemotherapy | Week 18 (After 4 cycles of chemotherapy) | These patients had their tumor(s) removed by surgery after receiving 4 cycles of chemotherapy to determine their response. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patients' Overall Tumor Response as Measured by Response Evaluation Criteria in Solid Tumors (RECIST) | Week 16 (4 weeks after 4th course) | Best response recorded from start of treatment until after 4th cycle of treatment. Defined by the sum of Complete Responses (CR), Partial Responses (PR), and Stable Disease (SD) in patients neoadjuvant chemotherapy. CR=disappearance of all lesions, PR=\>or=30% decrease in sumof all target lesins, Progressive Disease (PD) =\>or =20% increase in sum of all target or any new lesions, SD=not CR, PR or PD. |
| Clinical Response Based on Serum Cancer Antigen 125 (CA-125) Concentration | From Baseline to up to 12 weeks (4 courses of therapy) | Ca-125 serum results compared from baseline to after patient's last treatment. This is a tumor biomarker. A decrease in results indicates a clinical response. |
| Change in Drug Resistance After Neoadjuvant Chemotherapy | Day 1 to Time to Surgery (Approximately Week 18) | As measured by extreme drug resistance assay - Unable to report due to tissue samples being incomplete or unsatisfactory to do laboratory testing. |
| Change in Thrombospondin-1 (TSP-1), p53, and Tumor Vessel Density | Week 18 (At surgery) | Unable to report due to incomplete (nonviable) or unsatisfactory tissue samples. |
| Quality of Life Score of Patients Receiving Neoadjuvant Chemotherapy | Day 1, Week 12 (after 4th course) , Week 16 (4 weeks after last treatment) | Functional Assessment of Cancer Therapy-Ovarian (FACT-O) Questionnaire was used to assess the impact of treatment- and disease-related factors on the quality of life of patients with ovarian cancers undergoing chemotherapy. It is a 5 point scale (from worse to best: 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much responses). Physical well-being, social/family well-being, functional well-being, emotional well-being and additional concerns questions are asked. Unable to evaluate; patients did not consistently complete the questionnaires. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Patients Who Received Treatment Includes all patients enrolled and treated with at least one dose of chemotherapy (carboplatin - dose calculated per Calvert formula - given intravenously for 30 minutes and/or paclitaxel 175 milligrams per meter squared over 3 hours). | 7 |
| Total | 7 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Did not receive entire study regimen | 5 |
Baseline characteristics
| Characteristic | Patients Who Received Treatment |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 4 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants |
| Age, Continuous | 67 Years |
| Region of Enrollment United States | 7 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 7 / 7 |
| serious Total, serious adverse events | 6 / 7 |
Outcome results
Primary
Number of Patients Who Underwent Optimal Cytoreduction After Chemotherapy
These patients had their tumor(s) removed by surgery after receiving 4 cycles of chemotherapy to determine their response.
Time frame: Week 18 (After 4 cycles of chemotherapy)
Population: Includes those patients that received 4 cycles of therapy before removal of cancerous tissue. Evaluation of overall response is not possible due to low number of patients and therefore could not obtain statistical significance.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Evaluable Patients (Received 4 Cycles of Therapy and Surgery) | Number of Patients Who Underwent Optimal Cytoreduction After Chemotherapy | 2 Participants |
Secondary
Change in Drug Resistance After Neoadjuvant Chemotherapy
As measured by extreme drug resistance assay - Unable to report due to tissue samples being incomplete or unsatisfactory to do laboratory testing.
Time frame: Day 1 to Time to Surgery (Approximately Week 18)
Secondary
Change in Thrombospondin-1 (TSP-1), p53, and Tumor Vessel Density
Unable to report due to incomplete (nonviable) or unsatisfactory tissue samples.
Time frame: Week 18 (At surgery)
Secondary
Clinical Response Based on Serum Cancer Antigen 125 (CA-125) Concentration
Ca-125 serum results compared from baseline to after patient's last treatment. This is a tumor biomarker. A decrease in results indicates a clinical response.
Time frame: From Baseline to up to 12 weeks (4 courses of therapy)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Evaluable Patients (Received 4 Cycles of Therapy and Surgery) | Clinical Response Based on Serum Cancer Antigen 125 (CA-125) Concentration | Increased Concentration | 1 Participants |
| Evaluable Patients (Received 4 Cycles of Therapy and Surgery) | Clinical Response Based on Serum Cancer Antigen 125 (CA-125) Concentration | Decreased Concentration | 6 Participants |
Secondary
Patients' Overall Tumor Response as Measured by Response Evaluation Criteria in Solid Tumors (RECIST)
Best response recorded from start of treatment until after 4th cycle of treatment. Defined by the sum of Complete Responses (CR), Partial Responses (PR), and Stable Disease (SD) in patients neoadjuvant chemotherapy. CR=disappearance of all lesions, PR=\>or=30% decrease in sumof all target lesins, Progressive Disease (PD) =\>or =20% increase in sum of all target or any new lesions, SD=not CR, PR or PD.
Time frame: Week 16 (4 weeks after 4th course)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Evaluable Patients (Received 4 Cycles of Therapy and Surgery) | Patients' Overall Tumor Response as Measured by Response Evaluation Criteria in Solid Tumors (RECIST) | Partial Response | 2 Participants |
| Evaluable Patients (Received 4 Cycles of Therapy and Surgery) | Patients' Overall Tumor Response as Measured by Response Evaluation Criteria in Solid Tumors (RECIST) | Progressive Disease | 3 Participants |
| Evaluable Patients (Received 4 Cycles of Therapy and Surgery) | Patients' Overall Tumor Response as Measured by Response Evaluation Criteria in Solid Tumors (RECIST) | Stable Disease | 2 Participants |
Secondary
Quality of Life Score of Patients Receiving Neoadjuvant Chemotherapy
Functional Assessment of Cancer Therapy-Ovarian (FACT-O) Questionnaire was used to assess the impact of treatment- and disease-related factors on the quality of life of patients with ovarian cancers undergoing chemotherapy. It is a 5 point scale (from worse to best: 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much responses). Physical well-being, social/family well-being, functional well-being, emotional well-being and additional concerns questions are asked. Unable to evaluate; patients did not consistently complete the questionnaires.
Time frame: Day 1, Week 12 (after 4th course) , Week 16 (4 weeks after last treatment)