VTX-2337 and Pegylated Liposomal Doxorubicin (PLD) in Patients With Recurrent or Persistent Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer
NCT ID: NCT01666444
Last Updated: 2019-09-26
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE2
297 participants
INTERVENTIONAL
2012-10-31
2016-07-31
Brief Summary
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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.
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Detailed Description
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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
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Study Groups
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PLD 40 mg/m2 plus VTX-2337
The dosing schedule will be be based on a 28-day cycle. The starting dose schedule is PLD on Day 1 plus VTX-2337 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 on Day 3 only, without additional doses of VTX-2337 on Days 10 and Day 17.
pegylated liposomal doxorubicin (PLD)
VTX-2337
TLR8 Agonist
PLD 40 mg/m2 plus placebo
The dosing schedule will be based on a 28-day cycle. The starting dose schedule is PLD on Day 1 plus 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 placebo on Day 3 only.
pegylated liposomal doxorubicin (PLD)
Placebo
Interventions
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pegylated liposomal doxorubicin (PLD)
VTX-2337
TLR8 Agonist
Placebo
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. 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.
3. Patient must have measurable disease as defined by RECIST 1.1.
4. 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.
5. 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.
6. 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.
7. 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.
8. Patients must have a GOG performance status of 0 or 1.
9. 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.
10. Patients must meet the entry requirements and undergo the baseline procedures.
11. Patients must have signed an IRB-approved informed consent form and authorization permitting release of personal health information.
Exclusion Criteria
2. Patients who have received an investigational agent \< 30 days prior to registration.
3. Patients who have received oral or parenteral corticosteroids \< 2 weeks prior to registration or who require ongoing systemic immunosuppressive therapy for any reason.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.
9. Patients with clinically significant cardiovascular disease.
10. Patients who are pregnant or nursing.
11. Patients under the age of 18.
12. Patients with clinical symptoms or signs of gastrointestinal obstruction and/or who require parenteral hydration or nutrition.
18 Years
FEMALE
No
Sponsors
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Gynecologic Oncology Group
NETWORK
Celgene
INDUSTRY
Responsible Party
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Principal Investigators
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Bradley J. Monk, MD
Role: STUDY_CHAIR
St. Joseph's Hospital and Medical Center, Phoenix AZ
Amar Patel, MD
Role: STUDY_DIRECTOR
Celgene
Locations
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St. Joseph's Hospital and Medical Center
Phoenix, Arizona, United States
Winthrop P. Rockefeller Cancer Institute - University of Arkansas
Little Rock, Arkansas, United States
Providence Saint Joseph Medical Center
Burbank, California, United States
Kaiser Permanente Medical Center
Hayward, California, United States
Long Beach Memorial Medical Center
Long Beach, California, United States
Kaiser Permanente Medical Center
Oakland, California, United States
Kaiser Permanente Medical Center
Roseville, California, United States
Sutter Cancer Center
Sacramento, California, United States
Kaiser Permanente Medical Center
Sacramento, California, United States
Kaiser Permanente Medical Center
San Francisco, California, United States
Kaiser Permanente Medical Center
San Jose, California, United States
Kaiser Permanente Medical Center
Santa Clara, California, United States
Kaiser Permanente Medical Center
South San Francisco, California, United States
Stanford University School of Medicine
Stanford, California, United States
Kaiser Permanente Medical Center
Vallejo, California, United States
Kaiser Permanente Medical Center
Walnut Creek, California, United States
University of Colorado Cancer Center
Aurora, Colorado, United States
Hartford Hospital
Hartford, Connecticut, United States
St. Francis Hospital and Medical Center
Hartford, Connecticut, United States
The Hospital of Central Connecticut
New Britain, Connecticut, United States
Yale - New Haven Hospital
New Haven, Connecticut, United States
MD Anderson Cancer Center - Orlando
Orlando, Florida, United States
Women's Cancer Associates
St. Petersburg, Florida, United States
Northside Hospital
Atlanta, Georgia, United States
Georgia Regents University
Augusta, Georgia, United States
Northeast Georgia Medical Center
Gainesville, Georgia, United States
Central Georgia Gynecologic Oncology
Macon, Georgia, United States
Memorial Health University Medical Center
Savannah, Georgia, United States
St. Joseph's - Candler Gynecologic Oncology
Savannah, Georgia, United States
Kapiolani Medical Center for Women and Children
Honolulu, Hawaii, United States
Northwestern University - Robert H. Lurie Comprehensive Cancer Center
Chicago, Illinois, United States
Rush University Medical Center
Chicago, Illinois, United States
Sudarshan K. Sharma, MD, LTD
Hinsdale, Illinois, United States
Carle Cancer Center
Urbana, Illinois, United States
Indiana University Medical Center
Indianapolis, Indiana, United States
St. Vincent Gynecologic Oncology
Indianapolis, Indiana, United States
McFarland Clinic
Ames, Iowa, United States
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States
University of Kansas Medical Center
Westwood, Kansas, United States
Maine Medical Partners Women's Health
Scarborough, Maine, United States
University of Maryland Medical Center
Baltimore, Maryland, United States
Greater Baltimore Medical Center
Baltimore, Maryland, United States
Sinai Hospital of Baltimore
Baltimore, Maryland, United States
Johns Hopkins Medical Institution
Baltimore, Maryland, United States
Lahey Hospital & Medical Center
Burlington, Massachusetts, United States
University of Massachusetts Memorial Healthcare
Worcester, Massachusetts, United States
St. Joseph Mercy Hospital
Ann Arbor, Michigan, United States
Bronson Battle Creek
Battle Creek, Michigan, United States
Karmanos Cancer Institute - Wayne State University
Detroit, Michigan, United States
Henry Ford Health System
Detroit, Michigan, United States
Grand Rapids Clinical Oncology
Grand Rapids, Michigan, United States
Saint Mary's Health Care
Grand Rapids, Michigan, United States
Spectrum Health at Butterworth Campus
Grand Rapids, Michigan, United States
Gynecologic Oncology of West Michigan
Grand Rapids, Michigan, United States
West Michigan Cancer Center
Kalamazoo, Michigan, United States
Mercy Health Partners - Mercy Campus
Muskegon, Michigan, United States
Reed City Hospital - Spectrum Health
Reed City, Michigan, United States
Munson Medical Center
Traverse City, Michigan, United States
Minnesota Oncology Coon Rapids Clinic
Coon Rapids, Minnesota, United States
Fairview Southdale Hospital
Edina, Minnesota, United States
Abbott Northwestern Hospital
Minneapolis, Minnesota, United States
Metro Minnesota Clinical Oncology Program
Saint Louis Park, Minnesota, United States
Park Nicollet Frauenshuh Cancer Center
Saint Louis Park, Minnesota, United States
Minnesota Oncology Hematology - St. Paul Cancer Center
Saint Paul, Minnesota, United States
Woodbury Clinic - CornerStone Medical Specialty Centre
Woodbury, Minnesota, United States
St. Dominic-Jackson Memorial Hospital
Jackson, Mississippi, United States
University of Mississippi Medical Center
Jackson, Mississippi, United States
Ellis Fischel Cancer Center - University of Missouri
Columbia, Missouri, United States
Women's Cancer Care Center of Nevada
Las Vegas, Nevada, United States
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States
Cooper University Hospital
Camden, New Jersey, United States
Hackensack University Medical Center
Hackensack, New Jersey, United States
Southwest Gynecologic Oncology Associates
Albuquerque, New Mexico, United States
University of New Mexico Cancer Center
Albuquerque, New Mexico, United States
Memorial Medical Center
Las Cruces, New Mexico, United States
Women's Cancer Care Associates
Albany, New York, United States
SUNY Downstate Medical Center
Brooklyn, New York, United States
Roswell Park Cancer Institute
Buffalo, New York, United States
Monter Cancer Center
Lake Success, New York, United States
North Shore University Hospital
Manhasset, New York, United States
Long Island Jewish Medical Center
New Hyde Park, New York, United States
NYU Langone Medical Center - Cancer Institute
New York, New York, United States
Columbia University Medical Center
New York, New York, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Gynecologic Oncology of Central New York - SUNY Upstate
Syracuse, New York, United States
Hope Women's Cancer Center
Asheville, North Carolina, United States
Alamance Regional Cancer Center
Burlington, North Carolina, United States
Carolinas Medical Center / Levine Cancer Institute
Charlotte, North Carolina, United States
Carolinas Medical Center - Northeast
Concord, North Carolina, United States
Wake Forest University Health Science
Winston-Salem, North Carolina, United States
Summa Health System
Akron, Ohio, United States
University of Cincinnati
Cincinnati, Ohio, United States
University Hospitals of Cleveland
Cleveland, Ohio, United States
Fairview Hospital Moll Pavilion Cancer Center
Cleveland, Ohio, United States
Cleveland Clinic Foundation
Cleveland, Ohio, United States
Ohio State University Medical Center
Columbus, Ohio, United States
Women's Cancer Center at Kettering Medical Center
Kettering, Ohio, United States
Hillcrest Hospital - Cleveland Clinic
Mayfield Heights, Ohio, United States
Lake University Seidman Cancer Center
Mentor, Ohio, United States
Peggy and Charles Stephenson Cancer Center
Oklahoma City, Oklahoma, United States
Tulsa Cancer Institute
Tulsa, Oklahoma, United States
Abington Memorial Hospital; Hanjani Institute for Gynecologic Oncology
Abington, Pennsylvania, United States
Geisinger Medical Center
Danville, Pennsylvania, United States
University of Pennsylvania Medical Center
Philadelphia, Pennsylvania, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States
Hillman Cancer Center - University of Pittsburgh
Pittsburgh, Pennsylvania, United States
Western Pennsylvania Hospital
Pittsburgh, Pennsylvania, United States
Reading Hospital (McGlinn Family Regional Cancer Center)
West Reading, Pennsylvania, United States
Women and Infants Hospital of Rhode Island
Providence, Rhode Island, United States
Medical University of South Carolina
Charleston, South Carolina, United States
Bon Secours St. Francis Hospital
Greenville, South Carolina, United States
Gibbs Cancer Center
Spartanburg, South Carolina, United States
Avera Cancer Institute
Sioux Falls, South Dakota, United States
UT Southwestern Medical Center
Dallas, Texas, United States
University of Texas Medical Branch
Galveston, Texas, United States
MD Anderson Cancer Center
Houston, Texas, United States
The Methodist Hospital
Houston, Texas, United States
Huntsman Cancer Institute, University of Utah
Salt Lake City, Utah, United States
Mid Atlantic Pelvic Surgery Associates
Annandale, Virginia, United States
Virginia Gynecology Oncology
Richmond, Virginia, United States
Carilion Clinic Gynecological Oncology
Roanoke, Virginia, United States
Pacific Gynecology Specialists
Seattle, Washington, United States
Seattle Cancer Care Alliance
Seattle, Washington, United States
Northwest Hospital - UW Medicine
Seattle, Washington, United States
Women's Cancer Care of Seattle
Seattle, Washington, United States
University of Washington Medical Center
Seattle, Washington, United States
Green Bay Oncology at St. Vincent's Hospital
Green Bay, Wisconsin, United States
St Vincent Hospital
Green Bay, Wisconsin, United States
Green Bay Oncology at St. Mary's Hospital
Green Bay, Wisconsin, United States
University of Wisconsin-Madison
Madison, Wisconsin, United States
Holy Family Memorial Medical Center
Manitowoc, Wisconsin, United States
Bay Area Medical Center
Marinette, Wisconsin, United States
Marshfield Clinic
Marshfield, Wisconsin, United States
Aurora St. Luke's Medical Center Gynecologic Oncology
Milwaukee, Wisconsin, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, United States
Aspirus Regional Cancer Center
Wausau, Wisconsin, United States
Countries
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References
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Newhouse R, Nelissen E, El-Shakankery KH, Rogozinska E, Bain E, Veiga S, Morrison J. Pegylated liposomal doxorubicin for relapsed epithelial ovarian cancer. Cochrane Database Syst Rev. 2023 Jul 5;7(7):CD006910. doi: 10.1002/14651858.CD006910.pub3.
Monk BJ, Brady MF, Aghajanian C, Lankes HA, Rizack T, Leach J, Fowler JM, Higgins R, Hanjani P, Morgan M, Edwards R, Bradley W, Kolevska T, Foukas P, Swisher EM, Anderson KS, Gottardo R, Bryan JK, Newkirk M, Manjarrez KL, Mannel RS, Hershberg RM, Coukos G. A phase 2, randomized, double-blind, placebo- controlled study of chemo-immunotherapy combination using motolimod with pegylated liposomal doxorubicin in recurrent or persistent ovarian cancer: a Gynecologic Oncology Group partners study. Ann Oncol. 2017 May 1;28(5):996-1004. doi: 10.1093/annonc/mdx049.
Other Identifiers
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GOG-3003
Identifier Type: -
Identifier Source: org_study_id
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