VTX-2337 and Pegylated Liposomal Doxorubicin (PLD) in Patients With Recurrent or Persistent Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer

Fallopian Tube Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01666444
• Other study ID #: GOG-3003
• Status: Completed
• Phase: Phase 2
• 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
• 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.

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Epithelial Ovarian Cancer
• Fallopian Tube Cancer
• Fallopian Tube Neoplasms
• Ovarian Neoplasms
• Peritoneal Neoplasms
• Primary Peritoneal Cancer

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