VTX-2337 and Pegylated Liposomal Doxorubicin (PLD) in Patients With Recurrent or Persistent Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer
This trial is active, not recruiting.
|Conditions||epithelial ovarian cancer, fallopian tube cancer, primary peritoneal cancer|
|Treatments||pegylated liposomal doxorubicin (pld), vtx-2337, placebo|
|Sponsor||VentiRx Pharmaceuticals Inc.|
|Collaborator||Gynecologic Oncology Group|
|Start date||October 2012|
|End date||October 2016|
|Trial size||290 participants|
|Trial identifier||NCT01666444, GOG-3003|
The purpose of this study is to compare the overall survival of patients treated with VTX-2337 + pegylated liposomal doxorubicin (PLD) versus those treated with PLD alone in women with recurrent or persistent, epithelial ovarian, fallopian tube or primary peritoneal cancer.
VTX-2337, a small molecule agonist of Toll-like Receptor 8 (TLR8), activates multiple components of the innate immune system and is being developed as a novel therapeutic agent for use in oncology. Experimental data obtained in an animal model of ovarian cancer supports the combination of VTX-2337 with PLD. In this model, the combination of VTX-2337 and PLD resulted in a significant reduction in tumor growth compared to either agent alone and an increase in the number of T lymphocytes infiltrating the tumor. The combination of PLD and VTX-2337 has been tested in a small number of women with ovarian cancer in a Phase 1b study and appears to be generally well-tolerated.
|United States||No locations recruiting|
|Other countries||No locations recruiting|
|Phoenix, AZ||St. Joseph's Hospital and Medical Center||no longer recruiting|
|Little Rock, AR||Winthrop P. Rockefeller Cancer Institute - University of Arkansas||no longer recruiting|
|Burbank, CA||Providence Saint Joseph Medical Center||no longer recruiting|
|Hayward, CA||Kaiser Permanente Medical Center||no longer recruiting|
|Long Beach, CA||Long Beach Memorial Medical Center||no longer recruiting|
|Oakland, CA||Kaiser Permanente Medical Center||no longer recruiting|
|Roseville, CA||Kaiser Permanente Medical Center||no longer recruiting|
|Sacramento, CA||Sutter Cancer Center||no longer recruiting|
|Sacramento, CA||Kaiser Permanente Medical Center||no longer recruiting|
|San Francisco, CA||Kaiser Permanente Medical Center||no longer recruiting|
|San Jose, CA||Kaiser Permanente Medical Center||no longer recruiting|
|Santa Clara, CA||Kaiser Permanente Medical Center||no longer recruiting|
|South San Francisco, CA||Kaiser Permanente Medical Center||no longer recruiting|
|Stanford, CA||Stanford University School of Medicine||no longer recruiting|
|Vallejo, CA||Kaiser Permanente Medical Center||no longer recruiting|
|Walnut Creek, CA||Kaiser Permanente Medical Center||no longer recruiting|
|Aurora, CO||University of Colorado Cancer Center||no longer recruiting|
|Hartford, CT||Hartford Hospital||no longer recruiting|
|Hartford, CT||St. Francis Hospital and Medical Center||no longer recruiting|
|New Britain, CT||The Hospital of Central Connecticut||no longer recruiting|
|New Haven, CT||Yale - New Haven Hospital||no longer recruiting|
|Orlando, FL||MD Anderson Cancer Center - Orlando||no longer recruiting|
|St. Petersburg, FL||Women's Cancer Associates||no longer recruiting|
|Atlanta, GA||Northside Hospital||no longer recruiting|
|Augusta, GA||Georgia Regents University||no longer recruiting|
|Gainesville, GA||Northeast Georgia Medical Center||no longer recruiting|
|Macon, GA||Central Georgia Gynecologic Oncology||no longer recruiting|
|Savannah, GA||Memorial Health University Medical Center||no longer recruiting|
|Savannah, GA||St. Joseph's - Candler Gynecologic Oncology||no longer recruiting|
|Honolulu, HI||Kapiolani Medical Center for Women and Children||no longer recruiting|
|Chicago, IL||Northwestern University - Robert H. Lurie Comprehensive Cancer Center||no longer recruiting|
|Chicago, IL||Rush University Medical Center||no longer recruiting|
|Hinsdale, IL||Sudarshan K. Sharma, MD, LTD||no longer recruiting|
|Urbana, IL||Carle Cancer Center||no longer recruiting|
|Indianapolis, IN||Indiana University Medical Center||no longer recruiting|
|Indianapolis, IN||St. Vincent Gynecologic Oncology||no longer recruiting|
|Ames, IA||McFarland Clinic||no longer recruiting|
|Iowa City, IA||University of Iowa Hospitals and Clinics||no longer recruiting|
|Westwood, KS||University of Kansas Medical Center||no longer recruiting|
|Scarborough, ME||Maine Medical Partners Women's Health||no longer recruiting|
|Baltimore, MD||University of Maryland Medical Center||no longer recruiting|
|Baltimore, MD||Greater Baltimore Medical Center||no longer recruiting|
|Baltimore, MD||Sinai Hospital of Baltimore||no longer recruiting|
|Baltimore, MD||Johns Hopkins Medical Institution||no longer recruiting|
|Burlington, MA||Lahey Hospital & Medical Center||no longer recruiting|
|Worcester, MA||University of Massachusetts Memorial Healthcare||no longer recruiting|
|Ann Arbor, MI||St. Joseph Mercy Hospital||no longer recruiting|
|Battle Creek, MI||Bronson Battle Creek||no longer recruiting|
|Detroit, MI||Karmanos Cancer Institute - Wayne State University||no longer recruiting|
|Detroit, MI||Henry Ford Health System||no longer recruiting|
|Grand Rapids, MI||Grand Rapids Clinical Oncology||no longer recruiting|
|Grand Rapids, MI||Saint Mary's Health Care||no longer recruiting|
|Grand Rapids, MI||Spectrum Health at Butterworth Campus||no longer recruiting|
|Grand Rapids, MI||Gynecologic Oncology of West Michigan||no longer recruiting|
|Kalamazoo, MI||West Michigan Cancer Center||no longer recruiting|
|Muskegon, MI||Mercy Health Partners - Mercy Campus||no longer recruiting|
|Reed City, MI||Reed City Hospital - Spectrum Health||no longer recruiting|
|Traverse City, MI||Munson Medical Center||no longer recruiting|
|Coon Rapids, MN||Minnesota Oncology Coon Rapids Clinic||no longer recruiting|
|Edina, MN||Fairview Southdale Hospital||no longer recruiting|
|Minneapolis, MN||Abbott Northwestern Hospital||no longer recruiting|
|St. Louis Park, MN||Metro Minnesota Clinical Oncology Program||no longer recruiting|
|St. Louis Park, MN||Park Nicollet Frauenshuh Cancer Center||no longer recruiting|
|St. Paul, MN||Minnesota Oncology Hematology - St. Paul Cancer Center||no longer recruiting|
|Woodbury, MN||Woodbury Clinic - CornerStone Medical Specialty Centre||no longer recruiting|
|Jackson, MS||St. Dominic-Jackson Memorial Hospital||no longer recruiting|
|Jackson, MS||University of Mississippi Medical Center||no longer recruiting|
|Columbia, MO||Ellis Fischel Cancer Center - University of Missouri||no longer recruiting|
|Las Vegas, NV||Women's Cancer Care Center of Nevada||no longer recruiting|
|Lebanon, NH||Dartmouth-Hitchcock Medical Center||no longer recruiting|
|Camden, NJ||Cooper University Hospital||no longer recruiting|
|Hackensack, NJ||Hackensack University Medical Center||no longer recruiting|
|Albuquerque, NM||Southwest Gynecologic Oncology Associates||no longer recruiting|
|Albuquerque, NM||University of New Mexico Cancer Center||no longer recruiting|
|Las Cruces, NM||Memorial Medical Center||no longer recruiting|
|Albany, NY||Women's Cancer Care Associates||no longer recruiting|
|Brooklyn, NY||SUNY Downstate Medical Center||no longer recruiting|
|Buffalo, NY||Roswell Park Cancer Institute||no longer recruiting|
|Lake Success, NY||Monter Cancer Center||no longer recruiting|
|Manhasset, NY||North Shore University Hospital||no longer recruiting|
|New Hyde Park, NY||Long Island Jewish Medical Center||no longer recruiting|
|New York, NY||NYU Langone Medical Center - Cancer Institute||no longer recruiting|
|New York, NY||Columbia University Medical Center||no longer recruiting|
|New York, NY||Memorial Sloan Kettering Cancer Center||no longer recruiting|
|Syracuse, NY||Gynecologic Oncology of Central New York - SUNY Upstate||no longer recruiting|
|Asheville, NC||Hope Women's Cancer Center||no longer recruiting|
|Burlington, NC||Alamance Regional Cancer Center||no longer recruiting|
|Charlotte, NC||Carolinas Medical Center / Levine Cancer Institute||no longer recruiting|
|Concord, NC||Carolinas Medical Center - Northeast||no longer recruiting|
|Winston-Salem, NC||Wake Forest University Health Science||no longer recruiting|
|Akron, OH||Summa Health System||no longer recruiting|
|Cincinnati, OH||University of Cincinnati||no longer recruiting|
|Cleveland, OH||University Hospitals of Cleveland||no longer recruiting|
|Cleveland, OH||Fairview Hospital Moll Pavilion Cancer Center||no longer recruiting|
|Cleveland, OH||Cleveland Clinic Foundation||no longer recruiting|
|Columbus, OH||Ohio State University Medical Center||no longer recruiting|
|Kettering, OH||Women's Cancer Center at Kettering Medical Center||no longer recruiting|
|Mayfield Heights, OH||Hillcrest Hospital - Cleveland Clinic||no longer recruiting|
|Mentor, OH||Lake University Seidman Cancer Center||no longer recruiting|
|Oklahoma City, OK||Peggy and Charles Stephenson Cancer Center||no longer recruiting|
|Tulsa, OK||Tulsa Cancer Institute||no longer recruiting|
|Abington, PA||Abington Memorial Hospital; Hanjani Institute for Gynecologic Oncology||no longer recruiting|
|Danville, PA||Geisinger Medical Center||no longer recruiting|
|Philadelphia, PA||University of Pennsylvania Medical Center||no longer recruiting|
|Philadelphia, PA||Fox Chase Cancer Center||no longer recruiting|
|Pittsburgh, PA||Hillman Cancer Center - University of Pittsburgh||no longer recruiting|
|Pittsburgh, PA||Western Pennsylvania Hospital||no longer recruiting|
|West Reading, PA||Reading Hospital (McGlinn Family Regional Cancer Center)||no longer recruiting|
|Providence, RI||Women and Infants Hospital of Rhode Island||no longer recruiting|
|Charleston, SC||Medical University of South Carolina||no longer recruiting|
|Greenville, SC||Bon Secours St. Francis Hospital||no longer recruiting|
|Spartanburg, SC||Gibbs Cancer Center||no longer recruiting|
|Sioux Falls, SD||Avera Cancer Institute||no longer recruiting|
|Dallas, TX||UT Southwestern Medical Center||no longer recruiting|
|Galveston, TX||University of Texas Medical Branch||no longer recruiting|
|Houston, TX||MD Anderson Cancer Center||no longer recruiting|
|Houston, TX||The Methodist Hospital||no longer recruiting|
|Salt Lake City, UT||Huntsman Cancer Institute, University of Utah||no longer recruiting|
|Annandale, VA||Mid Atlantic Pelvic Surgery Associates||no longer recruiting|
|Richmond, VA||Virginia Gynecology Oncology||no longer recruiting|
|Roanoke, VA||Carilion Clinic Gynecological Oncology||no longer recruiting|
|Seattle, WA||Pacific Gynecology Specialists||no longer recruiting|
|Seattle, WA||Seattle Cancer Care Alliance||no longer recruiting|
|Seattle, WA||Northwest Hospital - UW Medicine||no longer recruiting|
|Seattle, WA||Women's Cancer Care of Seattle||no longer recruiting|
|Seattle, WA||University of Washington Medical Center||no longer recruiting|
|Green Bay, WI||Green Bay Oncology at St. Vincent's Hospital||no longer recruiting|
|Green Bay, WI||St Vincent Hospital||no longer recruiting|
|Green Bay, WI||Green Bay Oncology at St. Mary's Hospital||no longer recruiting|
|Madison, WI||University of Wisconsin-Madison||no longer recruiting|
|Manitowoc, WI||Holy Family Memorial Medical Center||no longer recruiting|
|Marinette, WI||Bay Area Medical Center||no longer recruiting|
|Marshfield, WI||Marshfield Clinic||no longer recruiting|
|Milwaukee, WI||Aurora St. Luke's Medical Center Gynecologic Oncology||no longer recruiting|
|Milwaukee, WI||Medical College of Wisconsin||no longer recruiting|
|Wausau, WI||Aspirus Regional Cancer Center||no longer recruiting|
|Endpoint classification||safety/efficacy study|
|Intervention model||parallel assignment|
|Masking||double blind (subject, caregiver, investigator, outcomes assessor)|
Overall survival (OS) of patients treated with VTX-2337 + PLD versus those treated with PLD alone
time frame: Approximately 15 months after the last patient is randomized.
Progression-free survival (PFS) of patients treated with VTX-2337 + PLD versus those treated with PLD alone using Immune-Related Response Evaluation Criteria In Solid Tumors (irRECIST).
time frame: Approximately 15 months after the last patient is randomized.
Frequency and severity of drug-related adverse events (AEs) of patients treated with VTX-2337 + PLD versus those treated with PLD alone.
time frame: Up to 6 months after the last patient is randomized.
Female participants at least 18 years old.
- Patients must have recurrent or persistent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma.
- Patients with the following histologic cell types are eligible: serous adenocarcinoma, endometrioid adenocarcinoma, mucinous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial adenocarcinoma, transitional cell carcinoma, malignant Brenner's tumor or adenocarcinoma not otherwise specified.
- Patient must have measurable disease as defined by RECIST 1.1.
- Patients must have received treatment with a platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin or another organoplatinum compound. This initial treatment may have included intraperitoneal therapy, consolidation, non-cytotoxic agents or extended therapy administered after surgical or non-surgical assessment. Patients are allowed to receive, but are not required to receive, one additional cytotoxic regimen for management of recurrent or persistent disease. Patients are allowed to have received, but are not required to have received, biologic/targeted therapy (e.g., bevacizumab and/or PARP inhibitor) as part of their primary treatment regimen or for management of recurrent or persistent disease.
- Patients must have platinum-resistant disease, defined as having a platinum-free interval (PFI) of < 12 months after first- or second-line platinum-based chemotherapy, or having disease progression while receiving second-line platinum-based chemotherapy.
- Patients must have adequate bone marrow, renal, hepatic, and neurologic functions as defined by the following:
- Bone marrow function: absolute neutrophil count (ANC) ≥ 1,500/mm3. This ANC cannot have been induced or supported by granulocyte colony stimulating factors. Platelets ≥ 100,000/mm3. Hemoglobin ≥ 9 g/dL.
- Renal function: creatinine ≤ 1.5 x institutional upper limit normal (ULN).
- Hepatic function: bilirubin < 1.2 mg/dL, SGOT (AST) and SGPT (ALT) ≤ 3.0 x ULN and alkaline phosphatase ≤ 2.5 x ULN.
- Patients must have recovered from effects of recent surgery, radiotherapy or chemotherapy:
- Patients should be free of active infection requiring parenteral antibiotics.
- Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration. Continuation of hormone replacement therapy is permitted.
- Any other prior therapy directed at the malignant tumor, including chemotherapy, biologic/targeted agents and immunologic agents, must be discontinued at least three weeks prior to registration.
- Any prior radiation therapy must be completed at least four weeks prior to registration.
- Patients must have a GOG performance status of 0 or 1.
- Patients of childbearing potential must have a negative pregnancy test prior to the study entry and be practicing an effective form of contraception. If applicable, patients must discontinue breastfeeding prior to study entry.
- Patients must meet the entry requirements and undergo the baseline procedures.
- Patients must have signed an IRB-approved informed consent form and authorization permitting release of personal health information.
- Patients who have had treatment with VTX-2337, doxorubicin, PLD, or any other anthracycline.
- Patients who have received an investigational agent < 30 days prior to registration.
- Patients who have received oral or parenteral corticosteroids < 2 weeks prior to registration or who require ongoing systemic immunosuppressive therapy for any reason.
- Patients with active autoimmune disease. "Active" refers to any condition currently requiring therapy. Examples of autoimmune disease include systemic lupus erythematosus, multiple sclerosis, inflammatory bowel disease and rheumatoid arthritis.
- Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer, are excluded if there is any evidence of the other malignancy being present within the last three years.
- Patients who have received prior radiotherapy OTHER THAN for the treatment of ovarian, fallopian tube or primary peritoneal cancer within the last three years are excluded.
- Patients who have received prior chemotherapy OTHER THAN for the treatment of ovarian, fallopian tube or primary peritoneal cancer within the last three years are excluded.
- Patients with history or evidence upon physical examination of CNS disease, including primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases, or history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months of the first date of treatment on this study.
- Patients with clinically significant cardiovascular disease.
- Patients who are pregnant or nursing.
- Patients under the age of 18.
- Patients with clinical symptoms or signs of gastrointestinal obstruction and/or who require parenteral hydration or nutrition.
|Official title||A Randomized, Double-Blind, Placebo-Controlled Phase II Study of VTX-2337 in Combination With Pegylated Liposomal Doxorubicin (PLD) in Patients With Recurrent or Persistent Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer|
|Description||OBJECTIVES Primary Objectives: - To compare the overall survival (OS) of patients treated with VTX-2337 + PLD versus those treated with PLD alone in women with recurrent or persistent, epithelial ovarian, fallopian tube or primary peritoneal cancer. - To compare the progression-free survival (PFS) between the two treatment groups using Immune-Related Response Evaluation Criteria in Solid Tumors (irRECIST). Secondary Objectives: - To compare the progression-free survival (PFS) between the two treatment groups using Response Evaluation Criteria In Solid Tumors (RECIST 1.1). - To compare the nature, frequency and severity of drug-related adverse events (AEs) between the two treatment groups. Exploratory Objectives: - To compare the best overall response rate (ORR) and duration of response (based on the probability of being in response function [PBRF]) between the two treatment groups using irRECIST and RECIST 1.1. - To compare the disease control rate (DCR) between the two treatment groups using irRECIST and RECIST 1.1. - To assess the impact of immune status and response on the clinical effects (OS, PFS, DCR, ORR, PBRF, AEs) of study treatment. - To assess the effect of TLR8 polymorphisms and BRCA1/BRCA2 mutations on the clinical effects (OS, PFS, DCR, ORR, PBRF, AEs) of study treatment. - To assess the effect of immune cell subsets, as measured by immunohistochemistry and micro RNA in primary tumor tissue (e.g. immune score), on the clinical effects (OS, PFS, DCR, ORR, PBRF, AEs) of study treatment. - To assess whether the presence of autoantibodies to tumor-derived proteins are predictive of the clinical effects (OS, PFS, DCR, ORR, PBRF, AEs) of study treatment. OUTLINE: This is Phase 2 multicenter clinical study to evaluate the efficacy and safety of the combination of VTX-2337 + PLD compared to PLD + Placebo. The dosing schedule will be the same for both treatment arms, and will be based on a 28-day cycle. The starting dose schedule is PLD on Day 1 plus VTX-2337 or placebo on Day 3, Day 10, and Day 17 for the first 4 cycles. Starting with cycle 5, the dose regimen will be PLD on Day 1 plus VTX-2337 or placebo on Day 3. Blood samples are collected periodically during cycle 1 for pharmacodynamics, pharmacogenomics, and other research studies. Patients will receive therapy until disease progression based on Immune-Related RECIST or until adverse effects prohibit further therapy. Following treatment completion, all patients will be followed with physical exams and histories every three months for the first two years, and then every six months for the next three years, and then|
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