Clincosm LogoSign in Get a demo

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

Sponsor
Celgene (Industry)
Overall Status
Completed
CT.gov ID
NCT01666444
Collaborator
Gynecologic Oncology Group (Other)
297
Enrollment
136
Locations
2
Arms
45
Actual Duration (Months)
2.2
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease Intervention/Treatment Phase
  • Drug: pegylated liposomal doxorubicin (PLD)
  • Drug: VTX-2337
  • Drug: Placebo
 Phase 2

Detailed 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

Study Design

Study Type:
Interventional
Actual Enrollment :
297 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Oct 31, 2012
Actual Primary Completion Date :
Jul 31, 2016
Actual Study Completion Date :
Jul 31, 2016

Arms and Interventions

Arm Intervention/Treatment
Experimental: 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.

Drug: pegylated liposomal doxorubicin (PLD)
Other Names:
  • Doxil
  • Lipodox

    • Drug: VTX-2337
    TLR8 Agonist
    Active Comparator: 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.

    Drug: pegylated liposomal doxorubicin (PLD)
    Other Names:
  • Doxil
  • Lipodox

    • Drug: Placebo

    Outcome Measures

    Primary Outcome Measures

    1. Overall Survival [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.]

      Comparison of duration of survival between the 2 treatment groups

    Secondary Outcome Measures

    1. Progression-free Survival (PFS) [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.]

      Comparison of PFS between the 2 treatment groups

    2. Frequency and Severity of Adverse Events (AEs) [Assessed during each cycle of therapy and within 30 days after the last cycle of therapy]

      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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    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.

    1. 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.

    2. 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.

    1. 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.

    1. Patients must have a GOG performance status of 0 or 1.

    2. 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.

    3. Patients must meet the entry requirements and undergo the baseline procedures.

    4. 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 St. Joseph's Hospital and Medical Center Phoenix Arizona United States 85013
    2 Winthrop P. Rockefeller Cancer Institute - University of Arkansas Little Rock Arkansas United States 72205
    3 Providence Saint Joseph Medical Center Burbank California United States 91505
    4 Kaiser Permanente Medical Center Hayward California United States 94545
    5 Long Beach Memorial Medical Center Long Beach California United States 90806
    6 Kaiser Permanente Medical Center Oakland California United States 94611
    7 Kaiser Permanente Medical Center Roseville California United States 95661
    8 Sutter Cancer Center Sacramento California United States 95816
    9 Kaiser Permanente Medical Center Sacramento California United States 95825
    10 Kaiser Permanente Medical Center San Francisco California United States 94115
    11 Kaiser Permanente Medical Center San Jose California United States 95119
    12 Kaiser Permanente Medical Center Santa Clara California United States 95051
    13 Kaiser Permanente Medical Center South San Francisco California United States 94080
    14 Stanford University School of Medicine Stanford California United States 94305
    15 Kaiser Permanente Medical Center Vallejo California United States 94586
    16 Kaiser Permanente Medical Center Walnut Creek California United States 94596
    17 University of Colorado Cancer Center Aurora Colorado United States 80045
    18 Hartford Hospital Hartford Connecticut United States 06102
    19 St. Francis Hospital and Medical Center Hartford Connecticut United States 06105
    20 The Hospital of Central Connecticut New Britain Connecticut United States 06050
    21 Yale - New Haven Hospital New Haven Connecticut United States 06520
    22 MD Anderson Cancer Center - Orlando Orlando Florida United States 32806
    23 Women's Cancer Associates Saint Petersburg Florida United States 33701
    24 Northside Hospital Atlanta Georgia United States 30342
    25 Georgia Regents University Augusta Georgia United States 30912
    26 Northeast Georgia Medical Center Gainesville Georgia United States 30501
    27 Central Georgia Gynecologic Oncology Macon Georgia United States 31201
    28 Memorial Health University Medical Center Savannah Georgia United States 31404
    29 St. Joseph's - Candler Gynecologic Oncology Savannah Georgia United States 31405
    30 Kapiolani Medical Center for Women and Children Honolulu Hawaii United States 96826
    31 Northwestern University - Robert H. Lurie Comprehensive Cancer Center Chicago Illinois United States 60611
    32 Rush University Medical Center Chicago Illinois United States 60612
    33 Sudarshan K. Sharma, MD, LTD Hinsdale Illinois United States 60521
    34 Carle Cancer Center Urbana Illinois United States 61801
    35 Indiana University Medical Center Indianapolis Indiana United States 46202
    36 St. Vincent Gynecologic Oncology Indianapolis Indiana United States 46260
    37 McFarland Clinic Ames Iowa United States 50010
    38 University of Iowa Hospitals and Clinics Iowa City Iowa United States 52242
    39 University of Kansas Medical Center Westwood Kansas United States 66205
    40 Maine Medical Partners Women's Health Scarborough Maine United States 04074
    41 University of Maryland Medical Center Baltimore Maryland United States 21201
    42 Greater Baltimore Medical Center Baltimore Maryland United States 21204
    43 Sinai Hospital of Baltimore Baltimore Maryland United States 21215
    44 Johns Hopkins Medical Institution Baltimore Maryland United States 21287
    45 Lahey Hospital & Medical Center Burlington Massachusetts United States 01805
    46 University of Massachusetts Memorial Healthcare Worcester Massachusetts United States 01605
    47 St. Joseph Mercy Hospital Ann Arbor Michigan United States 48106
    48 Bronson Battle Creek Battle Creek Michigan United States 49017
    49 Karmanos Cancer Institute - Wayne State University Detroit Michigan United States 48201
    50 Henry Ford Health System Detroit Michigan United States 48202
    51 Grand Rapids Clinical Oncology Grand Rapids Michigan United States 49503
    52 Saint Mary's Health Care Grand Rapids Michigan United States 49503
    53 Spectrum Health at Butterworth Campus Grand Rapids Michigan United States 49503
    54 Gynecologic Oncology of West Michigan Grand Rapids Michigan United States 49546
    55 West Michigan Cancer Center Kalamazoo Michigan United States 49007
    56 Mercy Health Partners - Mercy Campus Muskegon Michigan United States 49444
    57 Reed City Hospital - Spectrum Health Reed City Michigan United States 49677
    58 Munson Medical Center Traverse City Michigan United States 49684
    59 Minnesota Oncology Coon Rapids Clinic Coon Rapids Minnesota United States 55433
    60 Fairview Southdale Hospital Edina Minnesota United States 55435
    61 Abbott Northwestern Hospital Minneapolis Minnesota United States 55404
    62 Metro Minnesota Clinical Oncology Program Saint Louis Park Minnesota United States 55416
    63 Park Nicollet Frauenshuh Cancer Center Saint Louis Park Minnesota United States 55426
    64 Minnesota Oncology Hematology - St. Paul Cancer Center Saint Paul Minnesota United States 55102
    65 Woodbury Clinic - CornerStone Medical Specialty Centre Woodbury Minnesota United States 55125
    66 St. Dominic-Jackson Memorial Hospital Jackson Mississippi United States 32916
    67 University of Mississippi Medical Center Jackson Mississippi United States 39216
    68 Ellis Fischel Cancer Center - University of Missouri Columbia Missouri United States 65211
    69 Women's Cancer Care Center of Nevada Las Vegas Nevada United States 89169
    70 Dartmouth-Hitchcock Medical Center Lebanon New Hampshire United States 03756
    71 Cooper University Hospital Camden New Jersey United States 08103
    72 Hackensack University Medical Center Hackensack New Jersey United States 07601
    73 Southwest Gynecologic Oncology Associates Albuquerque New Mexico United States 87016
    74 University of New Mexico Cancer Center Albuquerque New Mexico United States 87106
    75 Memorial Medical Center Las Cruces New Mexico United States 88011
    76 Women's Cancer Care Associates Albany New York United States 12208
    77 SUNY Downstate Medical Center Brooklyn New York United States 11203
    78 Roswell Park Cancer Institute Buffalo New York United States 14263
    79 Monter Cancer Center Lake Success New York United States 11042
    80 North Shore University Hospital Manhasset New York United States 11030
    81 Long Island Jewish Medical Center New Hyde Park New York United States 11040
    82 NYU Langone Medical Center - Cancer Institute New York New York United States 10016
    83 Columbia University Medical Center New York New York United States 10032
    84 Memorial Sloan Kettering Cancer Center New York New York United States 10065
    85 Gynecologic Oncology of Central New York - SUNY Upstate Syracuse New York United States 13057
    86 Hope Women's Cancer Center Asheville North Carolina United States 28806
    87 Alamance Regional Cancer Center Burlington North Carolina United States 27215
    88 Carolinas Medical Center / Levine Cancer Institute Charlotte North Carolina United States 28204
    89 Carolinas Medical Center - Northeast Concord North Carolina United States 28025
    90 Wake Forest University Health Science Winston-Salem North Carolina United States 27157
    91 Summa Health System Akron Ohio United States 44304
    92 University of Cincinnati Cincinnati Ohio United States 45267
    93 University Hospitals of Cleveland Cleveland Ohio United States 44106
    94 Fairview Hospital Moll Pavilion Cancer Center Cleveland Ohio United States 44111
    95 Cleveland Clinic Foundation Cleveland Ohio United States 44195
    96 Ohio State University Medical Center Columbus Ohio United States 43210
    97 Women's Cancer Center at Kettering Medical Center Kettering Ohio United States 45429
    98 Hillcrest Hospital - Cleveland Clinic Mayfield Heights Ohio United States 44124
    99 Lake University Seidman Cancer Center Mentor Ohio United States 44060
    100 Peggy and Charles Stephenson Cancer Center Oklahoma City Oklahoma United States 73104
    101 Tulsa Cancer Institute Tulsa Oklahoma United States 74146
    102 Abington Memorial Hospital; Hanjani Institute for Gynecologic Oncology Abington Pennsylvania United States 19001
    103 Geisinger Medical Center Danville Pennsylvania United States 17822
    104 University of Pennsylvania Medical Center Philadelphia Pennsylvania United States 19104
    105 Fox Chase Cancer Center Philadelphia Pennsylvania United States 19111
    106 Hillman Cancer Center - University of Pittsburgh Pittsburgh Pennsylvania United States 15213
    107 Western Pennsylvania Hospital Pittsburgh Pennsylvania United States 15224
    108 Reading Hospital (McGlinn Family Regional Cancer Center) West Reading Pennsylvania United States 19611
    109 Women and Infants Hospital of Rhode Island Providence Rhode Island United States 02905
    110 Medical University of South Carolina Charleston South Carolina United States 29425
    111 Bon Secours St. Francis Hospital Greenville South Carolina United States 29601
    112 Gibbs Cancer Center Spartanburg South Carolina United States 29303
    113 Avera Cancer Institute Sioux Falls South Dakota United States 57105
    114 UT Southwestern Medical Center Dallas Texas United States 75390
    115 University of Texas Medical Branch Galveston Texas United States 77555
    116 MD Anderson Cancer Center Houston Texas United States 77030
    117 The Methodist Hospital Houston Texas United States 77030
    118 Huntsman Cancer Institute, University of Utah Salt Lake City Utah United States 84112
    119 Mid Atlantic Pelvic Surgery Associates Annandale Virginia United States 22003
    120 Virginia Gynecology Oncology Richmond Virginia United States 23229
    121 Carilion Clinic Gynecological Oncology Roanoke Virginia United States 24016
    122 Pacific Gynecology Specialists Seattle Washington United States 98104
    123 Seattle Cancer Care Alliance Seattle Washington United States 98109
    124 Northwest Hospital - UW Medicine Seattle Washington United States 98133
    125 Women's Cancer Care of Seattle Seattle Washington United States 98133
    126 University of Washington Medical Center Seattle Washington United States 98195
    127 Green Bay Oncology at St. Vincent's Hospital Green Bay Wisconsin United States 54301
    128 St Vincent Hospital Green Bay Wisconsin United States 54301
    129 Green Bay Oncology at St. Mary's Hospital Green Bay Wisconsin United States 54303
    130 University of Wisconsin-Madison Madison Wisconsin United States 53792
    131 Holy Family Memorial Medical Center Manitowoc Wisconsin United States 54221
    132 Bay Area Medical Center Marinette Wisconsin United States 54143
    133 Marshfield Clinic Marshfield Wisconsin United States 54449
    134 Aurora St. Luke's Medical Center Gynecologic Oncology Milwaukee Wisconsin United States 53215
    135 Medical College of Wisconsin Milwaukee Wisconsin United States 53226
    136 Aspirus Regional Cancer Center Wausau Wisconsin United States 54401

    Sponsors and Collaborators

    • Celgene
    • Gynecologic Oncology Group

    Investigators

    • Study Chair: Bradley J. Monk, MD, St. Joseph's Hospital and Medical Center, Phoenix AZ
    • Study Director: Amar Patel, MD, Celgene

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Celgene
    ClinicalTrials.gov Identifier:
    NCT01666444
    Other Study ID Numbers:
    • GOG-3003
    First Posted:
    Aug 16, 2012
    Last Update Posted:
    Sep 26, 2019
    Last Verified:
    Sep 1, 2019
    Keywords provided by Celgene
    recurrent epithelial ovarian cancer
    recurrent fallopian tube cancer
    recurrent primary peritoneal cavity cancer
    ovarian serous cystadenocarcinoma
    ovarian endometrioid adenocarcinoma
    ovarian mucinous cystadenocarcinoma
    ovarian undifferentiated adenocarcinoma
    ovarian clear cell cystadenocarcinoma
    ovarian mixed epithelial carcinoma
    Brenner tumor
    Additional relevant MeSH terms:
    Ovarian Neoplasms
    Carcinoma, Ovarian Epithelial
    Fallopian Tube Neoplasms
    Peritoneal Neoplasms
    Doxorubicin
    Liposomal doxorubicin

    Study Results

    Participant Flow

    Recruitment Details Enrollment was initiated on 2012-Aug-13 and terminated on 2014-Apr-11. During this time, 297 patients were enrolled.
    Pre-assignment Detail Prior to enrollment and treatment assignment, a completed eligibility checklist was electronically checked for completeness and compliance with eligibility criteria. Prior to treatment assignment, patients were stratified by prior platinum free interval (<6 months or >6-12 months) and performance status (0 or 1). Treatments were double-blinded.
    Arm/Group Title Pegylated Liposomal Doxorubicin (PLD) + Placebo Pegylated Liposomal Doxorubicin (PLD)+VTX-2337 (VTX)
    Arm/Group Description Pegylated Liposomal Doxorubicin (PLD) 40 mg/m2 plus placebo Pegylated Liposomal Doxorubicin (PLD) 40 mg/m2 plus VTX-2337 3.0 mg/m2
    Period Title: Overall Study
    STARTED 149 148
    COMPLETED 147 147
    NOT COMPLETED 2 1

    Baseline Characteristics

    Arm/Group Title Pegylated Liposomal Doxorubicin (PLD) + Placebo Pegylated Liposomal Doxorubicin (PLD)+VTX-2337 (VTX) Total
    Arm/Group Description Pegylated Liposomal Doxorubicin (PLD) 40 mg/m2 plus placebo Pegylated Liposomal Doxorubicin (PLD) 40 mg/m2 plus VTX-2337 3.0 mg/m2 Total of all reporting groups
    Overall Participants 149 148 297
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    61.6
    63.5
    62.7
    Age, Customized (Count of Participants)
    <40 years
    4
    2.7%
    1
    0.7%
    5
    1.7%
    40-49 years
    22
    14.8%
    11
    7.4%
    33
    11.1%
    50-59 years
    39
    26.2%
    42
    28.4%
    81
    27.3%
    60-69 years
    50
    33.6%
    51
    34.5%
    101
    34%
    70-79 years
    31
    20.8%
    38
    25.7%
    69
    23.2%
    > 79 years
    3
    2%
    5
    3.4%
    8
    2.7%
    Sex: Female, Male (Count of Participants)
    Female
    149
    100%
    148
    100%
    297
    100%
    Male
    0
    0%
    0
    0%
    0
    0%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    4
    2.7%
    3
    2%
    7
    2.4%
    Not Hispanic or Latino
    143
    96%
    145
    98%
    288
    97%
    Unknown or Not Reported
    2
    1.3%
    0
    0%
    2
    0.7%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    1
    0.7%
    1
    0.7%
    2
    0.7%
    Asian
    3
    2%
    3
    2%
    6
    2%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    4
    2.7%
    6
    4.1%
    10
    3.4%
    White
    141
    94.6%
    137
    92.6%
    278
    93.6%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    1
    0.7%
    1
    0.3%
    Eastern Cooperative Oncology Group (ECOG) Performance Status (Count of Participants)
    0 = Fully active, no restrictions
    104
    69.8%
    105
    70.9%
    209
    70.4%
    1=Restricted activity;ambulatory;can do light work
    45
    30.2%
    43
    29.1%
    88
    29.6%
    Prior Platinum-Free Interval as per Case Report Forms (Count of Participants)
    <= 6 months
    79
    53%
    72
    48.6%
    151
    50.8%
    > 6 months
    70
    47%
    76
    51.4%
    146
    49.2%
    Prior Chemotherapy Regimens (Count of Participants)
    1
    81
    54.4%
    69
    46.6%
    150
    50.5%
    2
    64
    43%
    74
    50%
    138
    46.5%
    3
    4
    2.7%
    5
    3.4%
    9
    3%

    Outcome Measures

    1. Primary Outcome
    Title Overall Survival
    Description Comparison of duration of survival between the 2 treatment groups
    Time Frame 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.

    Outcome Measure Data

    Analysis Population Description
    All enrolled patients
    Arm/Group Title Pegylated Liposomal Doxorubicin (PLD) + Placebo Pegylated Liposomal Doxorubicin (PLD)+VTX-2337 (VTX)
    Arm/Group Description Pegylated Liposomal Doxorubicin (PLD) 40 mg/m2 plus placebo Pegylated Liposomal Doxorubicin (PLD) 40 mg/m2 plus VTX-2337 3.0 mg/m2
    Measure Participants 149 148
    Median (Inter-Quartile Range) [days]
    574
    552
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pegylated Liposomal Doxorubicin (PLD) + Placebo, Pegylated Liposomal Doxorubicin (PLD)+VTX-2337 (VTX)
    Comments The null hypothesis is that the hazards of death are equal for both treatment groups. The primary assessment of this hypothesis was done with a stratified logrank test and the study was to be considered sufficiently mature to assess this hypothesis when at least 211 deaths had occurred among all individuals enrolled. Type I error was to be set to 0.08 for a one-sided test and the power for detecting a 30% reduction in the hazard (hazard ratio=0.70) due to VTX-2337 was 88.2%.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.923
    Comments P-value is for a one-sided hypothesis test.
    Method Log Rank
    Comments The logrank test is stratified for platinum-free interval (<= 6 months vs > 6 months), and performance status (0 vs 1).
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.22
    Confidence Interval (1-Sided) 92%
    to 1.48
    Parameter Dispersion Type:
    Value:
    Estimation Comments Treatment Hazard ratio for overall survival (PLD+VTX relative to PLD+placebo). Survival is measured from date of enrollment and randomization on the study until death from any cause, or date of last contact.
    2. Secondary Outcome
    Title Progression-free Survival (PFS)
    Description Comparison of PFS between the 2 treatment groups
    Time Frame 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.

    Outcome Measure Data

    Analysis Population Description
    All enrolled patients.
    Arm/Group Title Pegylated Liposomal Doxorubicin (PLD) + Placebo Pegylated Liposomal Doxorubicin (PLD)+VTX-2337 (VTX)
    Arm/Group Description Pegylated Liposomal Doxorubicin (PLD) 40 mg/m2 plus placebo Pegylated Liposomal Doxorubicin (PLD) 40 mg/m2 plus VTX-2337 3.0 mg/m2
    Measure Participants 149 148
    Median (Inter-Quartile Range) [days]
    159
    147
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pegylated Liposomal Doxorubicin (PLD) + Placebo, Pegylated Liposomal Doxorubicin (PLD)+VTX-2337 (VTX)
    Comments The null hypothesis is that the hazards of first progression or death are equal for both treatment groups. The primary assessment was to use a stratified logrank test and the study was to be considered sufficiently mature when survival is mature for analysis. Type I error was to be set to 0.02 for a one-sided test and the power for detecting a 31% reduction in the hazard (hazard ratio=0.69) due to VTX-2337 was expected to be approximately 83%.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.943
    Comments P-value is for a one-sided hypothesis test.
    Method Log Rank
    Comments The logrank test is stratified for platinum-free interval (<= 6 months vs > 6 months), and performance status (0 vs 1).
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.21
    Confidence Interval (1-Sided) 98%
    to 1.56
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    Title Frequency and Severity of Adverse Events (AEs)
    Description 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
    Time Frame Assessed during each cycle of therapy and within 30 days after the last cycle of therapy

    Outcome Measure Data

    Analysis Population Description
    All patients who initiated study treatment. There were 147 patients who initiated treatment on each arm.
    Arm/Group Title Pegylated Liposomal Doxorubicin (PLD) + Placebo Pegylated Liposomal Doxorubicin (PLD)+VTX-2337 (VTX)
    Arm/Group Description Pegylated Liposomal Doxorubicin (PLD) 40 mg/m2 plus placebo Pegylated Liposomal Doxorubicin (PLD) 40 mg/m2 plus VTX-2337 3.0 mg/m2
    Measure Participants 147 147
    Grade 1
    8
    5.4%
    3
    2%
    Grade 2
    40
    26.8%
    44
    29.7%
    Grade 3
    83
    55.7%
    90
    60.8%
    Grade 4
    10
    6.7%
    3
    2%
    Grade 5
    6
    4%
    7
    4.7%

    Adverse Events

    Time Frame Adverse Event assessments began with initiation of any study treatment up until 30 days following the last cycle of treatment.
    Adverse Event Reporting Description
    Arm/Group Title Pegylated Liposomal Doxorubicin (PLD) + Placebo Pegylated Liposomal Doxorubicin (PLD)+VTX-2337 (VTX)
    Arm/Group Description Pegylated Liposomal Doxorubicin (PLD) 40 mg/m2 plus placebo Pegylated Liposomal Doxorubicin (PLD) 40 mg/m2 plus VTX-2337 3.0 mg/m2
    All Cause Mortality
    Pegylated Liposomal Doxorubicin (PLD) + Placebo Pegylated Liposomal Doxorubicin (PLD)+VTX-2337 (VTX)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Pegylated Liposomal Doxorubicin (PLD) + Placebo Pegylated Liposomal Doxorubicin (PLD)+VTX-2337 (VTX)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 30/147 (20.4%) 36/147 (24.5%)
    Blood and lymphatic system disorders
    Anemia 3/147 (2%) 2/147 (1.4%)
    Cardiac disorders
    Atrial Fibrillation 1/147 (0.7%) 1/147 (0.7%)
    Gastrointestinal disorders
    Constipation 0/147 (0%) 2/147 (1.4%)
    Diarrhea 1/147 (0.7%) 4/147 (2.7%)
    Vomiting 5/147 (3.4%) 7/147 (4.8%)
    Upper Gastrointestinal Hemorrhage 0/147 (0%) 1/147 (0.7%)
    Bloating 0/147 (0%) 1/147 (0.7%)
    Small Intestinal Obstruction 3/147 (2%) 0/147 (0%)
    Abdominal Pain 3/147 (2%) 6/147 (4.1%)
    Mucositis Oral 1/147 (0.7%) 0/147 (0%)
    Gastrointestinal Disorders - Other 1/147 (0.7%) 1/147 (0.7%)
    Ileus 0/147 (0%) 1/147 (0.7%)
    Abdominal Distension 1/147 (0.7%) 2/147 (1.4%)
    Nausea 8/147 (5.4%) 9/147 (6.1%)
    Esophageal Ulcer 0/147 (0%) 1/147 (0.7%)
    Esophagitis 1/147 (0.7%) 0/147 (0%)
    Ascites 2/147 (1.4%) 1/147 (0.7%)
    General disorders
    Pain 0/147 (0%) 2/147 (1.4%)
    Malaise 1/147 (0.7%) 1/147 (0.7%)
    Injection Site Reaction 0/147 (0%) 1/147 (0.7%)
    Non-Cardiac Chest Pain 1/147 (0.7%) 0/147 (0%)
    Edema Limbs 0/147 (0%) 1/147 (0.7%)
    Fatigue 2/147 (1.4%) 4/147 (2.7%)
    Death Nos 0/147 (0%) 1/147 (0.7%)
    Fever 1/147 (0.7%) 3/147 (2%)
    Chills 0/147 (0%) 1/147 (0.7%)
    Infections and infestations
    Sinusitis 1/147 (0.7%) 0/147 (0%)
    Sepsis 5/147 (3.4%) 1/147 (0.7%)
    Lung Infection 0/147 (0%) 1/147 (0.7%)
    Cecal Infection 0/147 (0%) 1/147 (0.7%)
    Urinary Tract Infection 2/147 (1.4%) 2/147 (1.4%)
    Enterocolitis Infectious 1/147 (0.7%) 0/147 (0%)
    Biliary Tract Infection 1/147 (0.7%) 0/147 (0%)
    Injury, poisoning and procedural complications
    Spinal Fracture 1/147 (0.7%) 0/147 (0%)
    Investigations
    Lymphocyte Count Decreased 1/147 (0.7%) 0/147 (0%)
    Inr Increased 0/147 (0%) 1/147 (0.7%)
    Creatinine Increased 4/147 (2.7%) 0/147 (0%)
    Neutrophil Count Decreased 1/147 (0.7%) 2/147 (1.4%)
    Blood Bilirubin Increased 0/147 (0%) 1/147 (0.7%)
    White Blood Cell Decreased 0/147 (0%) 1/147 (0.7%)
    Aspartate Aminotransferase Increased 0/147 (0%) 1/147 (0.7%)
    Alkaline Phosphatase Increased 0/147 (0%) 1/147 (0.7%)
    Alanine Aminotransferase Increased 0/147 (0%) 1/147 (0.7%)
    Metabolism and nutrition disorders
    Hyponatremia 1/147 (0.7%) 1/147 (0.7%)
    Hypomagnesemia 1/147 (0.7%) 0/147 (0%)
    Hypokalemia 1/147 (0.7%) 0/147 (0%)
    Hypocalcemia 0/147 (0%) 1/147 (0.7%)
    Hypoalbuminemia 0/147 (0%) 1/147 (0.7%)
    Hyperglycemia 1/147 (0.7%) 0/147 (0%)
    Dehydration 1/147 (0.7%) 2/147 (1.4%)
    Anorexia 0/147 (0%) 3/147 (2%)
    Musculoskeletal and connective tissue disorders
    Pain In Extremity 1/147 (0.7%) 1/147 (0.7%)
    Generalized Muscle Weakness 0/147 (0%) 2/147 (1.4%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasms Benign, Malignant And Unspecified (Incl 0/147 (0%) 1/147 (0.7%)
    Nervous system disorders
    Stroke 0/147 (0%) 1/147 (0.7%)
    Dysarthria 0/147 (0%) 1/147 (0.7%)
    Cognitive Disturbance 0/147 (0%) 1/147 (0.7%)
    Psychiatric disorders
    Confusion 0/147 (0%) 1/147 (0.7%)
    Renal and urinary disorders
    Urinary Tract Obstruction 1/147 (0.7%) 1/147 (0.7%)
    Acute Kidney Injury 0/147 (0%) 2/147 (1.4%)
    Respiratory, thoracic and mediastinal disorders
    Respiratory, Thoracic And Mediastinal Disorders - 1/147 (0.7%) 0/147 (0%)
    Respiratory Failure 1/147 (0.7%) 1/147 (0.7%)
    Pleural Effusion 3/147 (2%) 3/147 (2%)
    Hypoxia 1/147 (0.7%) 0/147 (0%)
    Dyspnea 0/147 (0%) 3/147 (2%)
    Aspiration 0/147 (0%) 1/147 (0.7%)
    Vascular disorders
    Thromboembolic Event 1/147 (0.7%) 0/147 (0%)
    Hypotension 0/147 (0%) 1/147 (0.7%)
    Hypertension 1/147 (0.7%) 0/147 (0%)
    Other (Not Including Serious) Adverse Events
    Pegylated Liposomal Doxorubicin (PLD) + Placebo Pegylated Liposomal Doxorubicin (PLD)+VTX-2337 (VTX)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 147/147 (100%) 147/147 (100%)
    Blood and lymphatic system disorders
    Anemia 103/147 (70.1%) 105/147 (71.4%)
    Febrile Neutropenia 0/147 (0%) 1/147 (0.7%)
    Cardiac disorders
    Atrial Fibrillation 1/147 (0.7%) 2/147 (1.4%)
    Ventricular Tachycardia 1/147 (0.7%) 0/147 (0%)
    Sinus Bradycardia 1/147 (0.7%) 2/147 (1.4%)
    Palpitations 8/147 (5.4%) 6/147 (4.1%)
    Heart Failure 0/147 (0%) 1/147 (0.7%)
    Atrial Flutter 0/147 (0%) 1/147 (0.7%)
    Cardiac Disorders - Other 1/147 (0.7%) 1/147 (0.7%)
    Pericardial Effusion 0/147 (0%) 1/147 (0.7%)
    Sinus Tachycardia 11/147 (7.5%) 6/147 (4.1%)
    Chest Pain - Cardiac 1/147 (0.7%) 1/147 (0.7%)
    Ear and labyrinth disorders
    Middle Ear Inflammation 1/147 (0.7%) 0/147 (0%)
    Ear And Labyrinth Disorders - Other 0/147 (0%) 1/147 (0.7%)
    Vertigo 1/147 (0.7%) 1/147 (0.7%)
    Tinnitus 4/147 (2.7%) 5/147 (3.4%)
    Hearing Impaired 0/147 (0%) 4/147 (2.7%)
    Ear Pain 3/147 (2%) 1/147 (0.7%)
    External Ear Inflammation 1/147 (0.7%) 0/147 (0%)
    Endocrine disorders
    Hyperthyroidism 0/147 (0%) 1/147 (0.7%)
    Eye disorders
    Eye Disorders - Other 3/147 (2%) 1/147 (0.7%)
    Watering Eyes 2/147 (1.4%) 2/147 (1.4%)
    Flashing Lights 1/147 (0.7%) 2/147 (1.4%)
    Eye Pain 0/147 (0%) 3/147 (2%)
    Cataract 4/147 (2.7%) 0/147 (0%)
    Conjunctivitis 2/147 (1.4%) 1/147 (0.7%)
    Blurred Vision 6/147 (4.1%) 5/147 (3.4%)
    Dry Eye 3/147 (2%) 2/147 (1.4%)
    Floaters 1/147 (0.7%) 2/147 (1.4%)
    Gastrointestinal disorders
    Enterocolitis 1/147 (0.7%) 0/147 (0%)
    Dysphagia 17/147 (11.6%) 12/147 (8.2%)
    Dyspepsia 13/147 (8.8%) 22/147 (15%)
    Duodenal Obstruction 2/147 (1.4%) 0/147 (0%)
    Dry Mouth 10/147 (6.8%) 7/147 (4.8%)
    Colonic Obstruction 4/147 (2.7%) 2/147 (1.4%)
    Colitis 1/147 (0.7%) 0/147 (0%)
    Constipation 75/147 (51%) 79/147 (53.7%)
    Diarrhea 52/147 (35.4%) 45/147 (30.6%)
    Cheilitis 1/147 (0.7%) 0/147 (0%)
    Vomiting 48/147 (32.7%) 70/147 (47.6%)
    Upper Gastrointestinal Hemorrhage 1/147 (0.7%) 0/147 (0%)
    Bloating 26/147 (17.7%) 24/147 (16.3%)
    Small Intestinal Perforation 1/147 (0.7%) 0/147 (0%)
    Stomach Pain 7/147 (4.8%) 2/147 (1.4%)
    Small Intestinal Obstruction 13/147 (8.8%) 12/147 (8.2%)
    Anal Hemorrhage 1/147 (0.7%) 1/147 (0.7%)
    Anal Mucositis 0/147 (0%) 1/147 (0.7%)
    Abdominal Pain 54/147 (36.7%) 61/147 (41.5%)
    Periodontal Disease 1/147 (0.7%) 0/147 (0%)
    Rectal Hemorrhage 1/147 (0.7%) 3/147 (2%)
    Obstruction Gastric 1/147 (0.7%) 0/147 (0%)
    Small Intestinal Mucositis 0/147 (0%) 2/147 (1.4%)
    Mucositis Oral 57/147 (38.8%) 56/147 (38.1%)
    Lower Gastrointestinal Hemorrhage 1/147 (0.7%) 0/147 (0%)
    Gastrointestinal Disorders - Other 3/147 (2%) 5/147 (3.4%)
    Anal Pain 0/147 (0%) 1/147 (0.7%)
    Oral Hemorrhage 1/147 (0.7%) 1/147 (0.7%)
    Ileus 3/147 (2%) 5/147 (3.4%)
    Ileal Obstruction 1/147 (0.7%) 1/147 (0.7%)
    Gastrointestinal Pain 2/147 (1.4%) 1/147 (0.7%)
    Gastric Hemorrhage 1/147 (0.7%) 0/147 (0%)
    Oral Pain 10/147 (6.8%) 10/147 (6.8%)
    Abdominal Distension 15/147 (10.2%) 15/147 (10.2%)
    Nausea 93/147 (63.3%) 97/147 (66%)
    Gastroparesis 2/147 (1.4%) 1/147 (0.7%)
    Gastric Ulcer 1/147 (0.7%) 0/147 (0%)
    Gastroesophageal Reflux Disease 12/147 (8.2%) 15/147 (10.2%)
    Rectal Pain 1/147 (0.7%) 1/147 (0.7%)
    Lip Pain 0/147 (0%) 1/147 (0.7%)
    Esophageal Ulcer 0/147 (0%) 1/147 (0.7%)
    Esophagitis 7/147 (4.8%) 2/147 (1.4%)
    Fecal Incontinence 0/147 (0%) 1/147 (0.7%)
    Hemorrhoidal Hemorrhage 0/147 (0%) 1/147 (0.7%)
    Hemorrhoids 0/147 (0%) 3/147 (2%)
    Ascites 15/147 (10.2%) 8/147 (5.4%)
    Toothache 3/147 (2%) 3/147 (2%)
    Esophageal Pain 1/147 (0.7%) 5/147 (3.4%)
    Dental Caries 3/147 (2%) 0/147 (0%)
    Flatulence 6/147 (4.1%) 6/147 (4.1%)
    Gastritis 2/147 (1.4%) 2/147 (1.4%)
    General disorders
    General Disorders And Administration Site Conditio 3/147 (2%) 7/147 (4.8%)
    Pain 23/147 (15.6%) 26/147 (17.7%)
    Malaise 7/147 (4.8%) 6/147 (4.1%)
    Localized Edema 2/147 (1.4%) 1/147 (0.7%)
    Irritability 0/147 (0%) 1/147 (0.7%)
    Injection Site Reaction 13/147 (8.8%) 107/147 (72.8%)
    Infusion Site Extravasation 2/147 (1.4%) 0/147 (0%)
    Flu Like Symptoms 8/147 (5.4%) 45/147 (30.6%)
    Edema Trunk 2/147 (1.4%) 1/147 (0.7%)
    Non-Cardiac Chest Pain 6/147 (4.1%) 3/147 (2%)
    Edema Limbs 19/147 (12.9%) 37/147 (25.2%)
    Facial Pain 2/147 (1.4%) 1/147 (0.7%)
    Edema Face 0/147 (0%) 1/147 (0.7%)
    Fatigue 109/147 (74.1%) 127/147 (86.4%)
    Fever 19/147 (12.9%) 70/147 (47.6%)
    Gait Disturbance 2/147 (1.4%) 2/147 (1.4%)
    Chills 25/147 (17%) 92/147 (62.6%)
    Infusion Related Reaction 1/147 (0.7%) 5/147 (3.4%)
    Hepatobiliary disorders
    Hepatobiliary Disorders - Other 0/147 (0%) 1/147 (0.7%)
    Cholecystitis 1/147 (0.7%) 1/147 (0.7%)
    Immune system disorders
    Anaphylaxis 1/147 (0.7%) 0/147 (0%)
    Allergic Reaction 4/147 (2.7%) 4/147 (2.7%)
    Cytokine Release Syndrome 2/147 (1.4%) 24/147 (16.3%)
    Immune System Disorders - Other 1/147 (0.7%) 1/147 (0.7%)
    Infections and infestations
    Infections And Infestations - Other 4/147 (2.7%) 2/147 (1.4%)
    Wound Infection 1/147 (0.7%) 0/147 (0%)
    Upper Respiratory Infection 3/147 (2%) 4/147 (2.7%)
    Tooth Infection 1/147 (0.7%) 1/147 (0.7%)
    Stoma Site Infection 1/147 (0.7%) 0/147 (0%)
    Vulval Infection 2/147 (1.4%) 0/147 (0%)
    Soft Tissue Infection 1/147 (0.7%) 1/147 (0.7%)
    Skin Infection 6/147 (4.1%) 16/147 (10.9%)
    Sinusitis 6/147 (4.1%) 4/147 (2.7%)
    Sepsis 1/147 (0.7%) 0/147 (0%)
    Salivary Gland Infection 0/147 (0%) 1/147 (0.7%)
    Rash Pustular 1/147 (0.7%) 1/147 (0.7%)
    Peripheral Nerve Infection 1/147 (0.7%) 0/147 (0%)
    Papulopustular Rash 3/147 (2%) 2/147 (1.4%)
    Nail Infection 1/147 (0.7%) 2/147 (1.4%)
    Mucosal Infection 3/147 (2%) 2/147 (1.4%)
    Lymph Gland Infection 0/147 (0%) 1/147 (0.7%)
    Lung Infection 2/147 (1.4%) 3/147 (2%)
    Eye Infection 1/147 (0.7%) 0/147 (0%)
    Device Related Infection 1/147 (0.7%) 1/147 (0.7%)
    Gum Infection 0/147 (0%) 2/147 (1.4%)
    Vaginal Infection 4/147 (2.7%) 2/147 (1.4%)
    Urinary Tract Infection 12/147 (8.2%) 12/147 (8.2%)
    Catheter Related Infection 1/147 (0.7%) 0/147 (0%)
    Joint Infection 1/147 (0.7%) 0/147 (0%)
    Bronchial Infection 3/147 (2%) 0/147 (0%)
    Bone Infection 1/147 (0.7%) 0/147 (0%)
    Bladder Infection 3/147 (2%) 1/147 (0.7%)
    Lip Infection 0/147 (0%) 3/147 (2%)
    Injury, poisoning and procedural complications
    Wound Dehiscence 1/147 (0.7%) 0/147 (0%)
    Vascular Access Complication 2/147 (1.4%) 0/147 (0%)
    Vaginal Anastomotic Leak 0/147 (0%) 1/147 (0.7%)
    Urostomy Obstruction 1/147 (0.7%) 0/147 (0%)
    Spinal Fracture 2/147 (1.4%) 0/147 (0%)
    Radiation Recall Reaction (Dermatologic) 0/147 (0%) 1/147 (0.7%)
    Fracture 3/147 (2%) 0/147 (0%)
    Fall 6/147 (4.1%) 7/147 (4.8%)
    Wound Complication 0/147 (0%) 1/147 (0.7%)
    Burn 1/147 (0.7%) 1/147 (0.7%)
    Bruising 6/147 (4.1%) 8/147 (5.4%)
    Ankle Fracture 2/147 (1.4%) 0/147 (0%)
    Investigations
    Investigations - Other 2/147 (1.4%) 4/147 (2.7%)
    Weight Loss 19/147 (12.9%) 25/147 (17%)
    Weight Gain 5/147 (3.4%) 4/147 (2.7%)
    Platelet Count Decreased 30/147 (20.4%) 18/147 (12.2%)
    Lymphocyte Count Decreased 10/147 (6.8%) 15/147 (10.2%)
    Inr Increased 5/147 (3.4%) 3/147 (2%)
    Hemoglobin Increased 1/147 (0.7%) 0/147 (0%)
    Ggt Increased 2/147 (1.4%) 2/147 (1.4%)
    Electrocardiogram Qt Corrected Interval Prolonged 1/147 (0.7%) 0/147 (0%)
    Ejection Fraction Decreased 1/147 (0.7%) 3/147 (2%)
    Creatinine Increased 9/147 (6.1%) 11/147 (7.5%)
    Cholesterol High 1/147 (0.7%) 1/147 (0.7%)
    Neutrophil Count Decreased 60/147 (40.8%) 54/147 (36.7%)
    Urine Output Decreased 1/147 (0.7%) 0/147 (0%)
    Cd4 Lymphocytes Decreased 1/147 (0.7%) 2/147 (1.4%)
    Blood Bilirubin Increased 1/147 (0.7%) 0/147 (0%)
    White Blood Cell Decreased 83/147 (56.5%) 74/147 (50.3%)
    Aspartate Aminotransferase Increased 14/147 (9.5%) 17/147 (11.6%)
    Alkaline Phosphatase Increased 18/147 (12.2%) 18/147 (12.2%)
    Alanine Aminotransferase Increased 12/147 (8.2%) 9/147 (6.1%)
    Activated Partial Thromboplastin Time Prolonged 1/147 (0.7%) 1/147 (0.7%)
    Metabolism and nutrition disorders
    Metabolism And Nutrition Disorders - Other 3/147 (2%) 2/147 (1.4%)
    Hypophosphatemia 10/147 (6.8%) 6/147 (4.1%)
    Hyponatremia 18/147 (12.2%) 21/147 (14.3%)
    Hypomagnesemia 28/147 (19%) 24/147 (16.3%)
    Hypokalemia 28/147 (19%) 12/147 (8.2%)
    Hypoglycemia 7/147 (4.8%) 2/147 (1.4%)
    Hypocalcemia 14/147 (9.5%) 15/147 (10.2%)
    Hypoalbuminemia 27/147 (18.4%) 23/147 (15.6%)
    Hypertriglyceridemia 1/147 (0.7%) 2/147 (1.4%)
    Hypernatremia 5/147 (3.4%) 2/147 (1.4%)
    Hypermagnesemia 1/147 (0.7%) 2/147 (1.4%)
    Hyperkalemia 8/147 (5.4%) 4/147 (2.7%)
    Hyperglycemia 28/147 (19%) 19/147 (12.9%)
    Hypercalcemia 3/147 (2%) 3/147 (2%)
    Glucose Intolerance 1/147 (0.7%) 0/147 (0%)
    Dehydration 9/147 (6.1%) 11/147 (7.5%)
    Anorexia 46/147 (31.3%) 48/147 (32.7%)
    Alkalosis 0/147 (0%) 1/147 (0.7%)
    Musculoskeletal and connective tissue disorders
    Pain In Extremity 15/147 (10.2%) 23/147 (15.6%)
    Osteoporosis 2/147 (1.4%) 0/147 (0%)
    Neck Pain 0/147 (0%) 5/147 (3.4%)
    Myalgia 24/147 (16.3%) 20/147 (13.6%)
    Muscle Weakness Upper Limb 1/147 (0.7%) 1/147 (0.7%)
    Muscle Weakness Lower Limb 2/147 (1.4%) 3/147 (2%)
    Muscle Weakness Left-Sided 0/147 (0%) 1/147 (0.7%)
    Joint Range Of Motion Decreased 1/147 (0.7%) 0/147 (0%)
    Joint Effusion 0/147 (0%) 1/147 (0.7%)
    Generalized Muscle Weakness 12/147 (8.2%) 16/147 (10.9%)
    Flank Pain 3/147 (2%) 3/147 (2%)
    Chest Wall Pain 1/147 (0.7%) 2/147 (1.4%)
    Buttock Pain 1/147 (0.7%) 2/147 (1.4%)
    Bone Pain 8/147 (5.4%) 6/147 (4.1%)
    Back Pain 26/147 (17.7%) 30/147 (20.4%)
    Avascular Necrosis 0/147 (0%) 1/147 (0.7%)
    Arthritis 3/147 (2%) 4/147 (2.7%)
    Arthralgia 23/147 (15.6%) 17/147 (11.6%)
    Abdominal Soft Tissue Necrosis 0/147 (0%) 1/147 (0.7%)
    Musculoskeletal And Connective Tissue Disorder - 4/147 (2.7%) 2/147 (1.4%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasms Benign, Malignant And Unspecified (Incl 4/147 (2.7%) 0/147 (0%)
    Tumor Pain 0/147 (0%) 1/147 (0.7%)
    Nervous system disorders
    Nervous System Disorders - Other 2/147 (1.4%) 0/147 (0%)
    Tremor 3/147 (2%) 3/147 (2%)
    Transient Ischemic Attacks 0/147 (0%) 1/147 (0.7%)
    Somnolence 1/147 (0.7%) 0/147 (0%)
    Seizure 0/147 (0%) 1/147 (0.7%)
    Presyncope 0/147 (0%) 2/147 (1.4%)
    Peripheral Sensory Neuropathy 47/147 (32%) 45/147 (30.6%)
    Peripheral Motor Neuropathy 6/147 (4.1%) 5/147 (3.4%)
    Paresthesia 5/147 (3.4%) 7/147 (4.8%)
    Neuralgia 2/147 (1.4%) 0/147 (0%)
    Memory Impairment 3/147 (2%) 2/147 (1.4%)
    Lethargy 0/147 (0%) 1/147 (0.7%)
    Hypersomnia 0/147 (0%) 1/147 (0.7%)
    Headache 34/147 (23.1%) 27/147 (18.4%)
    Facial Nerve Disorder 0/147 (0%) 1/147 (0.7%)
    Dysphasia 0/147 (0%) 1/147 (0.7%)
    Dysgeusia 13/147 (8.8%) 7/147 (4.8%)
    Dysarthria 0/147 (0%) 1/147 (0.7%)
    Syncope 1/147 (0.7%) 1/147 (0.7%)
    Dizziness 14/147 (9.5%) 24/147 (16.3%)
    Depressed Level Of Consciousness 0/147 (0%) 1/147 (0.7%)
    Concentration Impairment 0/147 (0%) 1/147 (0.7%)
    Cognitive Disturbance 1/147 (0.7%) 3/147 (2%)
    Ataxia 1/147 (0.7%) 1/147 (0.7%)
    Akathisia 0/147 (0%) 1/147 (0.7%)
    Psychiatric disorders
    Psychiatric Disorders - Other 0/147 (0%) 1/147 (0.7%)
    Suicidal Ideation 0/147 (0%) 2/147 (1.4%)
    Psychosis 0/147 (0%) 1/147 (0.7%)
    Insomnia 16/147 (10.9%) 27/147 (18.4%)
    Hallucinations 0/147 (0%) 1/147 (0.7%)
    Depression 24/147 (16.3%) 24/147 (16.3%)
    Confusion 4/147 (2.7%) 6/147 (4.1%)
    Anxiety 24/147 (16.3%) 32/147 (21.8%)
    Agitation 1/147 (0.7%) 6/147 (4.1%)
    Renal and urinary disorders
    Renal And Urinary Disorders - Other 2/147 (1.4%) 6/147 (4.1%)
    Urine Discoloration 1/147 (0.7%) 0/147 (0%)
    Urinary Urgency 2/147 (1.4%) 5/147 (3.4%)
    Urinary Tract Obstruction 5/147 (3.4%) 0/147 (0%)
    Urinary Retention 1/147 (0.7%) 0/147 (0%)
    Urinary Incontinence 5/147 (3.4%) 11/147 (7.5%)
    Urinary Tract Pain 4/147 (2.7%) 1/147 (0.7%)
    Urinary Frequency 7/147 (4.8%) 13/147 (8.8%)
    Proteinuria 3/147 (2%) 1/147 (0.7%)
    Hemoglobinuria 2/147 (1.4%) 0/147 (0%)
    Hematuria 5/147 (3.4%) 1/147 (0.7%)
    Chronic Kidney Disease 3/147 (2%) 3/147 (2%)
    Acute Kidney Injury 1/147 (0.7%) 2/147 (1.4%)
    Reproductive system and breast disorders
    Reproductive System And Breast Disorders - Other 0/147 (0%) 1/147 (0.7%)
    Vaginal Pain 1/147 (0.7%) 0/147 (0%)
    Vaginal Hemorrhage 6/147 (4.1%) 5/147 (3.4%)
    Vaginal Dryness 3/147 (2%) 1/147 (0.7%)
    Pelvic Pain 4/147 (2.7%) 5/147 (3.4%)
    Vaginal Discharge 8/147 (5.4%) 5/147 (3.4%)
    Vaginal Inflammation 1/147 (0.7%) 1/147 (0.7%)
    Breast Pain 1/147 (0.7%) 0/147 (0%)
    Respiratory, thoracic and mediastinal disorders
    Respiratory, Thoracic And Mediastinal Disorders - 0/147 (0%) 1/147 (0.7%)
    Sore Throat 6/147 (4.1%) 6/147 (4.1%)
    Sneezing 1/147 (0.7%) 1/147 (0.7%)
    Sinus Disorder 0/147 (0%) 2/147 (1.4%)
    Postnasal Drip 5/147 (3.4%) 4/147 (2.7%)
    Pneumothorax 0/147 (0%) 1/147 (0.7%)
    Pneumonitis 1/147 (0.7%) 1/147 (0.7%)
    Pleural Effusion 7/147 (4.8%) 9/147 (6.1%)
    Pharyngolaryngeal Pain 1/147 (0.7%) 0/147 (0%)
    Pharyngeal Mucositis 1/147 (0.7%) 0/147 (0%)
    Nasal Congestion 10/147 (6.8%) 12/147 (8.2%)
    Pleuritic Pain 0/147 (0%) 2/147 (1.4%)
    Productive Cough 3/147 (2%) 1/147 (0.7%)
    Hypoxia 3/147 (2%) 2/147 (1.4%)
    Hoarseness 0/147 (0%) 2/147 (1.4%)
    Sleep Apnea 1/147 (0.7%) 0/147 (0%)
    Hiccups 1/147 (0.7%) 2/147 (1.4%)
    Epistaxis 5/147 (3.4%) 4/147 (2.7%)
    Dyspnea 40/147 (27.2%) 39/147 (26.5%)
    Cough 29/147 (19.7%) 36/147 (24.5%)
    Wheezing 3/147 (2%) 1/147 (0.7%)
    Atelectasis 3/147 (2%) 0/147 (0%)
    Aspiration 0/147 (0%) 1/147 (0.7%)
    Allergic Rhinitis 3/147 (2%) 5/147 (3.4%)
    Skin and subcutaneous tissue disorders
    Skin And Subcutaneous Tissue Disorders - Other 8/147 (5.4%) 15/147 (10.2%)
    Urticaria 2/147 (1.4%) 3/147 (2%)
    Stevens-Johnson Syndrome 1/147 (0.7%) 0/147 (0%)
    Skin Ulceration 4/147 (2.7%) 5/147 (3.4%)
    Skin Induration 1/147 (0.7%) 7/147 (4.8%)
    Skin Hyperpigmentation 20/147 (13.6%) 21/147 (14.3%)
    Scalp Pain 0/147 (0%) 1/147 (0.7%)
    Rash Acneiform 7/147 (4.8%) 9/147 (6.1%)
    Purpura 2/147 (1.4%) 0/147 (0%)
    Pruritus 24/147 (16.3%) 20/147 (13.6%)
    Photosensitivity 2/147 (1.4%) 1/147 (0.7%)
    Palmar-Plantar Erythrodysesthesia Syndrome 55/147 (37.4%) 54/147 (36.7%)
    Pain Of Skin 6/147 (4.1%) 4/147 (2.7%)
    Rash Maculo-Papular 58/147 (39.5%) 53/147 (36.1%)
    Nail Ridging 1/147 (0.7%) 2/147 (1.4%)
    Nail Loss 2/147 (1.4%) 2/147 (1.4%)
    Nail Discoloration 8/147 (5.4%) 2/147 (1.4%)
    Hyperhidrosis 4/147 (2.7%) 3/147 (2%)
    Erythema Multiforme 5/147 (3.4%) 8/147 (5.4%)
    Dry Skin 21/147 (14.3%) 24/147 (16.3%)
    Bullous Dermatitis 6/147 (4.1%) 2/147 (1.4%)
    Alopecia 14/147 (9.5%) 20/147 (13.6%)
    Surgical and medical procedures
    Surgical And Medical Procedures - Other 1/147 (0.7%) 3/147 (2%)
    Vascular disorders
    Vascular Disorders - Other 1/147 (0.7%) 0/147 (0%)
    Thromboembolic Event 7/147 (4.8%) 5/147 (3.4%)
    Superficial Thrombophlebitis 1/147 (0.7%) 0/147 (0%)
    Lymphedema 5/147 (3.4%) 4/147 (2.7%)
    Hypotension 6/147 (4.1%) 11/147 (7.5%)
    Hypertension 13/147 (8.8%) 18/147 (12.2%)
    Hot Flashes 13/147 (8.8%) 7/147 (4.8%)
    Hematoma 3/147 (2%) 4/147 (2.7%)
    Flushing 1/147 (0.7%) 1/147 (0.7%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Kristi Manjarrez
    Organization Vice President, Clinical Affairs
    Phone 206-689-2256
    Email kmanjarrez@ventirx.com
    Responsible Party:
    Celgene
    ClinicalTrials.gov Identifier:
    NCT01666444
    Other Study ID Numbers:
    • GOG-3003
    First Posted:
    Aug 16, 2012
    Last Update Posted:
    Sep 26, 2019
    Last Verified:
    Sep 1, 2019