Clinical trial NCT00288275: Correlation of the Chemoresponse Assay With PFS in Patients With Recurrent Epithelial Ovarian, Peritoneal, or Fallopian Tube Cancer
Official title: A Non-Interventional Prospective Study of the Correlation of the Precision Therapeutics, Inc. Chemoresponse Assay With Progression-Free Survival in Patients With Recurrent Epithelial Ovarian, Peritoneal, or Fallopian Tube Cancer.
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Ovarian Cancer
Fallopian Tube Cancer
Peritoneal Neoplasms
Keywords: Ovarian Cancer
Fallopian Tube Cancer
Peritoneal Cancer
Assay
Chemotherapy
Recurrent
Refractory
Persistent
Chemoresponse
Sensitivity
Precision Therapeutics
Lead sponsor: Precision Therapeutics
Sponsor class: INDUSTRY
First posted: 2006-02-07
Enrollment: 256
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Approximately 500 patients will be enrolled at 20-30 US sites. Patients have been diagnosed with persistent, refractory, or recurrent epithelial ovarian, peritoneal, or fallopian tube cancer.

Brief summary: Chemoresponse assays (lab test) measure the effect that chemotherapy treatment has on a patient's cancer cells in the lab. This test has shown success in a retrospective study in predicting how an individual patient's tumor will respond to a given chemotherapy and how treatment utilizing an agent that the test said that a patient's cells would be sensitive too corresponds to a longer progression free interval. This study will determine the ability of two tests used to predict the success of chemotherapy in recurrent, persistent, or refractory cancer of the ovaries, fallopian tube(s) or peritoneum by measuring how long patients live without progression.

Detailed description: The traditional treatment course for new cases of ovarian, fallopian tube, or peritoneal cancer is cytoreductive surgery followed by chemotherapy with paclitaxel in combination with carboplatin. Unfortunately, despite high initial response rates, the majority of patients recur and subsequent therapy is much less likely to be effective. The use of ineffective chemotherapy can result in unnecessary toxicity and costs, delay of more effective treatment, and the potential for the development of cross-resistance to additional drugs. The ability to individualize therapy by providing the treating physician with ex vivo response information on a panel of drugs should aid in the selection of effective therapy for individual patients, thus resulting in improved outcomes.

Resistance to chemotherapy cannot be predicted by either clinical or histological examination. Historically, the ex vivo sensitivity and resistance of tumor cells has been evaluated as a tool for predicting the clinical response of the patient to therapy. In this study, chemotherapy drugs will be tested using both the Precision Therapeutics' ChemoFx Assay and the Yale Apoptosis Assay. The assay results will be compared to clinical outcomes that will be reported at regular intervals. Blood, tumor pathology slides, and excess tumor cells (if available) will be used to characterize common polymorphisms in drug metabolizing enzymes as well as other molecular markers potentially associated with tumor response.

This is a one-arm validation trial with a goal of approximately 256 evaluable patients recruited from multiple sites. Patients will be drawn from the Yale -New Haven Medical Center and multiple additional sites as needed to meet accrual goals. The patients will be treated with FDA approved drugs and/or drug combinations based on the medical judgment of the treating physician. The study is not randomized and the results of the assay will not be used in the decision process for which agent to select for treatment, but are made available to the treating physician upon further progression.

Eligibility criteria: Inclusion Criteria:

* Patient has been diagnosed with persistent, refractory, or recurrent epithelial ovarian, peritoneal, or fallopian tube carcinoma.
* Patient must have documented disease defined by physical exam, clinically significant increases in CA-125 (as defined by protocol), CT, MRI scan, PET, x-ray or ultrasound for whom cytoreduction, excisional biopsy, incisional biopsy, or paracentesis is medically indicated, or in the alternative, have agreed to a core biopsy of the primary site, a secondary metastatic site, or a paracentesis or thoracentesis for fluid collection.
* Patient has disease of one of the following histologic epithelial cell types: serous adenocarcinoma, endometrioid adenocarcinoma, mucinous adenocarcinoma, undifferentiated carcinoma, transitional cell carcinoma, clear cell carcinoma, or adenocarcinoma, not otherwise specified (N.O.S.). Cytologic confirmation of diagnosis is acceptable for patients treated with neoadjuvant therapy who have not had a surgical procedure for a histologic confirmation.
* Patient has only received one or two prior chemotherapy regimens for their ovarian, peritoneal, or fallopian tube carcinoma. Multiple previous regimens of Taxol/Carboplatin will be counted as 1 prior chemotherapy regimen (e.g., A patient who receives first line Taxol/Carboplatin, then recurs, then receives Taxol/Carboplatin will be considered to have had only 1 prior regimen.)
* Patient must have completed prior chemotherapy regimens at least 3 weeks prior to tissue extraction.
* Patient must have an estimated life expectancy of greater than six months, as determined by the investigator.
* Patient requires chemotherapy and the investigator plans to administer one of the regimens of interest as deemed by her physician.
* Patient must be a female and at least 18 years of age. Ovarian cancer is a disease that occurs only in women and is exceedingly rare in females under the age of 18.
* Patient must have an ECOG Performance Status of 0, 1, or 2.
* Tumor tissue or ascitic fluid must be available for the assays. Ascites or Pleural alone may be collected and submitted as the sample tissue, but the patient must also have measurable disease as demonstrated by a CA-125 level 2X ULN or measurable lesions on imaging to be eligible.
* Patient must have signed an approved consent form.

Exclusion Criteria:

* Patient has ovarian stromal, mixed mullerian, or germ cell tumors
* Patient has borderline carcinoma (uncertain malignant potential)
* Pregnant or lactating patients
* Patients of childbearing potential not employing adequate contraception.
* Patients who are at risk of failure of compliance to the visit schedules and procedures.
* The investigator plans to use an assay to select the chemotherapy drug regimen. The investigator may submit the patient's tissue for testing with other assays, but may not use the results of those assays to select the chemotherapy regimen for the patient for this trial.
* Patients with synchronous primary endometrial cancer or a past history of primary endometrial cancer are excluded unless all of the following conditions are met: Stage not greater than I-B, Less than 3mm invasion without vascular or lymphatic invasion, NO poorly differentiated subtype, including papillary serous, clear cell, or othe FIGO Grade 3 lesion.

Primary outcomes:
measure: Progression Free Survival
timeFrame: 1. Every Treatment Cycle 2. Every 3 months for the first 2 years post treatment 3. Every 6 months for the next 3 years post treatment 4. Annually thereafter.
Secondary outcomes:
measure: Tumor Response
timeFrame: 1. Every treatment cycle 2. Every 3 months for the first 2 years post treatment 3. Every 6 months for the next 3 years post treatment 4. Annually thereafter.
Other outcomes:
Locations:
city: Irvine
country: United States
facility: University of California
state: California
city: Los Angeles
country: United States
facility: Kaiser Permanente
state: California
city: New Haven
country: United States
facility: Yale University Medical Center
state: Connecticut
city: Fort Myers
country: United States
facility: Florida Gynecologic Oncology
state: Florida
city: Jacksonville
country: United States
facility: St. Vincents Medical Center
state: Florida
city: Orlando
country: United States
facility: The Florida Hospital
state: Florida
city: St. Petersburg
country: United States
facility: Women's Cancer Associates
state: Florida
city: Atlanta
country: United States
facility: Atlanta Medical Center
state: Georgia
city: Riverdale
country: United States
facility: Southeastern Gynecologic Oncology Riverdale
state: Georgia
city: Chicago
country: United States
facility: Northwestern University/Prentice Women's Hospital
state: Illinois
city: Chicago
country: United States
facility: Rush University
state: Illinois
city: Indianapolis
country: United States
facility: St. Vincent Indianapolis Hospital
state: Indiana
city: Edgewood
country: United States
facility: St. Elizabeth Medical Center
state: Kentucky
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: St. Louis
country: United States
facility: Washington University
state: Missouri
city: St. Louis
country: United States
facility: Saint Louis University
state: Missouri
city: Camden
country: United States
facility: The Cooper Health System
state: New Jersey
city: West Orange
country: United States
facility: Saint Barnabas Medical Center
state: New Jersey
city: Brightwaters
country: United States
facility: Schwartz Gynecologic Oncology, PLLC
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center Barrett Cancer Center
state: Ohio
city: Cleveland
country: United States
facility: University Hospital Case Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Toledo
country: United States
facility: University of Toledo Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Portland
country: United States
facility: Legacy Health System
state: Oregon
city: Abington
country: United States
facility: Abington Memorial Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Cancer Center at Magee Womens Hospital
state: Pennsylvania
city: Wynnwood
country: United States
facility: Lankenau Hospital, Mainline Health System
state: Pennsylvania
city: Providence
country: United States
facility: Women & Infants Hospital
state: Rhode Island
city: Greenville
country: United States
facility: Cancer Centers of the Carolinas
state: South Carolina
city: Memphis
country: United States
facility: ACORN - The West Clinic
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: The Methodist Hospital
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Madison
country: United States
facility: University of Wisconsin, Madison
state: Wisconsin
Study officials:
affiliation: Yale University
name: Thomas J Rutherford, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Precision Therapeutics, Inc.
name: Hong Ma, MD
role: STUDY_DIRECTOR
References:
citation: Jemal A, Tiwari RC, Murray T, Ghafoor A, Samuels A, Ward E, Feuer EJ, Thun MJ; American Cancer Society. Cancer statistics, 2004. CA Cancer J Clin. 2004 Jan-Feb;54(1):8-29. doi: 10.3322/canjclin.54.1.8.
citation: Ness RB, Wisniewski SR, Eng H, Christopherson W. Cell viability assay for drug testing in ovarian cancer: in vitro kill versus clinical response. Anticancer Res. 2002 Mar-Apr;22(2B):1145-9.
citation: O'Meara AT, Sevin BU. Predictive value of the ATP chemosensitivity assay in epithelial ovarian cancer. Gynecol Oncol. 2001 Nov;83(2):334-42. doi: 10.1006/gyno.2001.6395.
citation: McLeod HL, King CR, Marsh S. Application of pharmacogenomics in the individualization of chemotherapy for gastrointestinal malignancies. Clin Colorectal Cancer. 2004 Jun;4 Suppl 1:S43-7. doi: 10.3816/ccc.2004.s.007.
citation: Kaplan EL, Meier P. Nonparametric estimation of incomplete observations. JASA 1958;43:457-481.
citation: Journal of Clinical Oncology, 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol 22, No 14S (July 15 Supplement), 2004: 5074.