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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Gynecologic Oncology Group
Information provided by (Responsible Party):
VentiRx Pharmaceuticals Inc.
ClinicalTrials.gov Identifier:
NCT01666444
First received: August 10, 2012
Last updated: September 25, 2014
Last verified: September 2014
  Purpose

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 Intervention Phase
Epithelial Ovarian Cancer
Fallopian Tube Cancer
Primary Peritoneal Cancer
Drug: pegylated liposomal doxorubicin (PLD)
Drug: VTX-2337
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by VentiRx Pharmaceuticals Inc.:

Primary Outcome Measures:
  • Overall survival (OS) of patients treated with VTX-2337 + PLD versus those treated with PLD alone [ Time Frame: Approximately 15 months after the last patient is randomized. ] [ Designated as safety issue: No ]
    Overall Survival analysis will occur when 146 deaths have occurred.


Secondary Outcome Measures:
  • Progression-free survival (PFS) of patients treated with VTX-2337 + PLD versus those treated with PLD alone using Immune-Related Response Evaluation Criteria In Solid Tumors (irRECIST). [ Time Frame: Approximately 15 months after the last patient is randomized. ] [ Designated as safety issue: No ]
    Progression is assessed at Week 12 and at 8-week intervals thereafter.

  • Frequency and severity of drug-related adverse events (AEs) of patients treated with VTX-2337 + PLD versus those treated with PLD alone. [ Time Frame: Up to 6 months after the last patient is randomized. ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 290
Study Start Date: October 2012
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

Detailed Description:

OBJECTIVES

Primary Objective:

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.

Secondary Objectives:

  • To compare the progression-free survival (PFS) between the two treatment groups using Immune-Related Response Evaluation Criteria In Solid Tumors (irRECIST).
  • 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.
  • To compare the disease control rate (DCR) between the two treatment groups using irRECIST.
  • 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 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 in primary tumor tissue (e.g. immune score), on 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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01666444

  Show 136 Study Locations
Sponsors and Collaborators
VentiRx Pharmaceuticals Inc.
Gynecologic Oncology Group
Investigators
Study Chair: Bradley J. Monk, MD St. Joseph's Hospital and Medical Center, Phoenix AZ
  More Information

No publications provided

Responsible Party: VentiRx Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT01666444     History of Changes
Other Study ID Numbers: GOG-3003
Study First Received: August 10, 2012
Last Updated: September 25, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by VentiRx Pharmaceuticals Inc.:
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:
Fallopian Tube Neoplasms
Neoplasms, Glandular and Epithelial
Ovarian Neoplasms
Peritoneal Neoplasms
Abdominal Neoplasms
Adnexal Diseases
Digestive System Diseases
Digestive System Neoplasms
Endocrine Gland Neoplasms
Endocrine System Diseases
Fallopian Tube Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Gonadal Disorders
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Ovarian Diseases
Peritoneal Diseases
Urogenital Neoplasms
Doxorubicin
Liposomal doxorubicin
Antibiotics, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on November 20, 2014