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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01666444
Other study ID # GOG-3003
Secondary ID
Status Completed
Phase Phase 2
First received
Last updated
Start date October 31, 2012
Est. completion date July 31, 2016

Study information

Verified date September 2019
Source Celgene
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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.


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


Recruitment information / eligibility

Status Completed
Enrollment 297
Est. completion date July 31, 2016
Est. primary completion date July 31, 2016
Accepts healthy volunteers No
Gender Female
Age group 18 Years and older
Eligibility Inclusion Criteria:

1. Patients must have recurrent or persistent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma.

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:

1. Patients who have had treatment with VTX-2337, doxorubicin, PLD, or any other anthracycline.

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.

Study Design


Intervention

Drug:
pegylated liposomal doxorubicin (PLD)

VTX-2337
TLR8 Agonist
Placebo


Locations

Country Name City State
United States Abington Memorial Hospital; Hanjani Institute for Gynecologic Oncology Abington Pennsylvania
United States Summa Health System Akron Ohio
United States Women's Cancer Care Associates Albany New York
United States Southwest Gynecologic Oncology Associates Albuquerque New Mexico
United States University of New Mexico Cancer Center Albuquerque New Mexico
United States McFarland Clinic Ames Iowa
United States St. Joseph Mercy Hospital Ann Arbor Michigan
United States Mid Atlantic Pelvic Surgery Associates Annandale Virginia
United States Hope Women's Cancer Center Asheville North Carolina
United States Northside Hospital Atlanta Georgia
United States Georgia Regents University Augusta Georgia
United States University of Colorado Cancer Center Aurora Colorado
United States Greater Baltimore Medical Center Baltimore Maryland
United States Johns Hopkins Medical Institution Baltimore Maryland
United States Sinai Hospital of Baltimore Baltimore Maryland
United States University of Maryland Medical Center Baltimore Maryland
United States Bronson Battle Creek Battle Creek Michigan
United States SUNY Downstate Medical Center Brooklyn New York
United States Roswell Park Cancer Institute Buffalo New York
United States Providence Saint Joseph Medical Center Burbank California
United States Alamance Regional Cancer Center Burlington North Carolina
United States Lahey Hospital & Medical Center Burlington Massachusetts
United States Cooper University Hospital Camden New Jersey
United States Medical University of South Carolina Charleston South Carolina
United States Carolinas Medical Center / Levine Cancer Institute Charlotte North Carolina
United States Northwestern University - Robert H. Lurie Comprehensive Cancer Center Chicago Illinois
United States Rush University Medical Center Chicago Illinois
United States University of Cincinnati Cincinnati Ohio
United States Cleveland Clinic Foundation Cleveland Ohio
United States Fairview Hospital Moll Pavilion Cancer Center Cleveland Ohio
United States University Hospitals of Cleveland Cleveland Ohio
United States Ellis Fischel Cancer Center - University of Missouri Columbia Missouri
United States Ohio State University Medical Center Columbus Ohio
United States Carolinas Medical Center - Northeast Concord North Carolina
United States Minnesota Oncology Coon Rapids Clinic Coon Rapids Minnesota
United States UT Southwestern Medical Center Dallas Texas
United States Geisinger Medical Center Danville Pennsylvania
United States Henry Ford Health System Detroit Michigan
United States Karmanos Cancer Institute - Wayne State University Detroit Michigan
United States Fairview Southdale Hospital Edina Minnesota
United States Northeast Georgia Medical Center Gainesville Georgia
United States University of Texas Medical Branch Galveston Texas
United States Grand Rapids Clinical Oncology Grand Rapids Michigan
United States Gynecologic Oncology of West Michigan 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 Green Bay Oncology at St. Mary's Hospital Green Bay Wisconsin
United States Green Bay Oncology at St. Vincent's Hospital Green Bay Wisconsin
United States St Vincent Hospital Green Bay Wisconsin
United States Bon Secours St. Francis Hospital Greenville South Carolina
United States Hackensack University Medical Center Hackensack New Jersey
United States Hartford Hospital Hartford Connecticut
United States St. Francis Hospital and Medical Center Hartford Connecticut
United States Kaiser Permanente Medical Center Hayward California
United States Sudarshan K. Sharma, MD, LTD Hinsdale Illinois
United States Kapiolani Medical Center for Women and Children Honolulu Hawaii
United States MD Anderson Cancer Center Houston Texas
United States The Methodist Hospital Houston Texas
United States Indiana University Medical Center Indianapolis Indiana
United States St. Vincent Gynecologic Oncology Indianapolis Indiana
United States University of Iowa Hospitals and Clinics Iowa City Iowa
United States St. Dominic-Jackson Memorial Hospital Jackson Mississippi
United States University of Mississippi Medical Center Jackson Mississippi
United States West Michigan Cancer Center Kalamazoo Michigan
United States Women's Cancer Center at Kettering Medical Center Kettering Ohio
United States Monter Cancer Center Lake Success New York
United States Memorial Medical Center Las Cruces New Mexico
United States Women's Cancer Care Center of Nevada Las Vegas Nevada
United States Dartmouth-Hitchcock Medical Center Lebanon New Hampshire
United States Winthrop P. Rockefeller Cancer Institute - University of Arkansas Little Rock Arkansas
United States Long Beach Memorial Medical Center Long Beach California
United States Central Georgia Gynecologic Oncology Macon Georgia
United States University of Wisconsin-Madison Madison Wisconsin
United States North Shore University Hospital Manhasset New York
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 Hillcrest Hospital - Cleveland Clinic Mayfield Heights Ohio
United States Lake University Seidman Cancer Center Mentor Ohio
United States Aurora St. Luke's Medical Center Gynecologic Oncology Milwaukee Wisconsin
United States Medical College of Wisconsin Milwaukee Wisconsin
United States Abbott Northwestern Hospital Minneapolis Minnesota
United States Mercy Health Partners - Mercy Campus Muskegon Michigan
United States The Hospital of Central Connecticut New Britain Connecticut
United States Yale - New Haven Hospital New Haven Connecticut
United States Long Island Jewish Medical Center New Hyde Park 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 NYU Langone Medical Center - Cancer Institute New York New York
United States Kaiser Permanente Medical Center Oakland California
United States Peggy and Charles Stephenson Cancer Center Oklahoma City Oklahoma
United States MD Anderson Cancer Center - Orlando Orlando Florida
United States Fox Chase Cancer Center Philadelphia Pennsylvania
United States University of Pennsylvania Medical Center Philadelphia Pennsylvania
United States St. Joseph's Hospital and Medical Center Phoenix Arizona
United States Hillman Cancer Center - University of Pittsburgh Pittsburgh Pennsylvania
United States Western Pennsylvania Hospital Pittsburgh Pennsylvania
United States Women and Infants Hospital of Rhode Island Providence Rhode Island
United States Reed City Hospital - Spectrum Health Reed City Michigan
United States Virginia Gynecology Oncology Richmond Virginia
United States Carilion Clinic Gynecological Oncology Roanoke Virginia
United States Kaiser Permanente Medical Center Roseville California
United States Kaiser Permanente Medical Center Sacramento California
United States Sutter Cancer Center Sacramento California
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 Women's Cancer Associates Saint Petersburg Florida
United States Huntsman Cancer Institute, University of Utah Salt Lake City Utah
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 Memorial Health University Medical Center Savannah Georgia
United States St. Joseph's - Candler Gynecologic Oncology Savannah Georgia
United States Maine Medical Partners Women's Health Scarborough Maine
United States Northwest Hospital - UW Medicine Seattle Washington
United States Pacific Gynecology Specialists Seattle Washington
United States Seattle Cancer Care Alliance Seattle Washington
United States University of Washington Medical Center Seattle Washington
United States Women's Cancer Care of Seattle Seattle Washington
United States Avera Cancer Institute Sioux Falls South Dakota
United States Kaiser Permanente Medical Center South San Francisco California
United States Gibbs Cancer Center Spartanburg South Carolina
United States Stanford University School of Medicine Stanford California
United States Gynecologic Oncology of Central New York - SUNY Upstate Syracuse New York
United States Munson Medical Center Traverse City Michigan
United States Tulsa Cancer Institute Tulsa Oklahoma
United States Carle Cancer Center Urbana Illinois
United States Kaiser Permanente Medical Center Vallejo California
United States Kaiser Permanente Medical Center Walnut Creek California
United States Aspirus Regional Cancer Center Wausau Wisconsin
United States Reading Hospital (McGlinn Family Regional Cancer Center) West Reading Pennsylvania
United States University of Kansas Medical Center Westwood Kansas
United States Wake Forest University Health Science Winston-Salem North Carolina
United States Woodbury Clinic - CornerStone Medical Specialty Centre Woodbury Minnesota
United States University of Massachusetts Memorial Healthcare Worcester Massachusetts

Sponsors (2)

Lead Sponsor Collaborator
Celgene Gynecologic Oncology Group

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Overall Survival Comparison of duration of survival between the 2 treatment groups Survival is measured from date of enrollment and randomization on the study until death from any cause, or if alive at last contact, date of last contact.
Secondary Progression-free Survival (PFS) Comparison of PFS between the 2 treatment groups Progression-free survival is measured from enrollment and randomization on the study until first indication of progression based on irRECIST criteria or death from any cause, or if progression-free at last contact, the date of last disease assessment.
Secondary Frequency and Severity of Adverse Events (AEs) An AE is any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. An AE can be unfavorable and unintended sign, symptom, or disease which is temporally associated with the use of investigational product (IP), whether or not considered related to the IP. A serious AE = an AE occurring at any dose that: • Results in death • Is life- threatening • Requires or prolongs existing inpatient hospitalization • Results in persistent or significant disability/incapacity • Is a congenital anomaly/birth defect; • Constitutes an important medical event. The Investigator assessed the relationship of each AE to IP and graded the severity according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0: Grade (GR) 1 = Mild; asymptomatic or mild symptoms; GR 2 = Moderate (minimal, local or noninvasive intervention indicated); GR 3 = Severe or medically significant; GR 4 = Life-threatening; GR 5 = Death Assessed during each cycle of therapy and within 30 days after the last cycle of therapy
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