VTX-2337 and Pegylated Liposomal Doxorubicin (PLD) in Patients With Recurrent or Persistent Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer
Condition: Epithelial Ovarian Cancer; Fallopian Tube Cancer; Primary Peritoneal Cancer
MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Fallopian Tube Neoplasms; Peritoneal Neoplasms
Intervention: pegylated liposomal doxorubicin (PLD); VTX-2337; Placebo
Intervention description: TLR8 Agonist
Intervention MeSH terms: Doxorubicin; Liposomal doxorubicin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 297.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: 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

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.
    

Eligibility 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.