Cvac as Maintenance Treatment in Patients With Epithelial Ovarian Cancer in Complete Remission Following First-line Chemotherapy or Second-line Treatment
Condition: Epithelial Ovarian Cancer
MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial
Intervention: Cvac; Placebo
Intervention description: Injections were done at 4 anatomical sites, 1 injection in each of the upper portions of both arms and both thighs.; Injections were done at 4 anatomical sites, 1 injection in each of the upper portions of both arms and both thighs.
Placebo consisted of the Cvac formulation buffer (5% HSA, 10% DMSO) with 0.9% simethicone provided in 1 mL vials that had been cryopreserved and stored at the manufacturing facility.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 91.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: EOC

Summary:

      As < 10% of the necessary patients required by the protocol were recruited and the data were
      not intended to support a labeling claim, it was determined that the abbreviated clinical
      study report (CSR) was the appropriate reporting format. No efficacy analyses were performed
      as the trial was terminated early with incomplete enrollment of < 10%.

      The purpose of this study is to determine if an investigational cell therapy called Cvac can
      help epithelial ovarian cancer (EOC) from returning when administered to patients who are in
      complete remission after surgical removal of their tumor followed by standard first-line
      (Part A) or second-line (Part B) chemotherapy. Following remission, patients will undergo
      leukapheresis for the manufacture of the study agent. After completion of chemotherapy and
      confirmation of remission, patients will enter the treatment phase of the study.
    

Eligibility criteria:

        Part A: First Remission

        Inclusion Criteria (Part A):

          1. Females ≥ 18 years of age at screening with a confirmed diagnosis of Stage III or IV
             epithelial ovarian, primary peritoneal, or fallopian tube cancer.

          2. Undergone optimal debulking surgery, defined as ≤ 1 cm of residual tumor.

          3. Undergone standard platinum and taxane first-line chemotherapy.

          4. Signed an informed consent form (ICF).

          5. Completed study procedures within the study timelines.

          6. Mucin 1-positive tumor as determined by central immunohistopathology.

          7. Adequate renal function in the opinion of the investigator based on serum creatinine
             and/or glomerular filtration rate.

          8. Adequate liver function, defined as serum glutamic oxaloacetic transaminase/aspartate
             aminotransferase (SGOT/AST) and serum glutamic pyruvic transaminase/alanine
             aminotransferase (SGPT/ALT) ≤ 2× ULN and serum bilirubin ≤ 1.5 × ULN, unless Gilbert's
             syndrome had been previously confirmed for the patient.

          9. Adequate bone marrow function, defined as white blood cells (WBCs) ≥ 3.0 K/µL,
             absolute neutrophil count (ANC) ≥ 1.5 × 109/L, hemoglobin ≥ 9 g/dL, and platelets ≥
             100 × 109/L.

         10. Life expectancy of at least 12 months at the time of screening as judged by the
             investigator.

         11. Not pregnant, and if of childbearing potential, agreed to use a highly effective
             method of birth control (implanted, injectable, or oral combination hormonal method
             alone or in possible combinations, intrauterine device, vasectomized partner, or
             abstinence) prior to study entry, for the duration of the study, and for 3 months
             after the last dose of study agent. Male partners of a study patient must use a condom
             in addition to the acceptable method of contraception for the female partner, as
             specified above.

        Exclusion Criteria (Part A):

          1. Non-epithelial ovarian cancer, including ovarian germ cell, sarcoma, mixed Müllerian
             tumors, or mucinous carcinoma of the peritoneum.

          2. Malignancy other than epithelial ovarian cancer, except those that had been in
             complete response for a minimum of 3 years, and except carcinoma in-situ of the cervix
             or basal cell and squamous cell carcinomas of the skin that had been adequately
             treated.

          3. Treatment with any investigational product (for any condition) within 4 weeks of
             screening.

          4. Concurrent systemic treatment with steroids or other immunosuppressant agents at a
             dose considered by the investigator to be higher than a standard physiological dose.

          5. Evidence of severe or uncontrolled cardiac disease, including myocardial infarction or
             unstable angina within 6 months of screening, congestive heart failure, or ventricular
             arrhythmias requiring medication.

          6. Clinically significant abnormalities as measured by electrocardiogram (ECG).

          7. Active uncontrolled infection.

          8. Uncontrolled hypertension.

          9. Diagnosed immunodeficiency or autoimmune disorder.

         10. Infection with human immunodeficiency virus (HIV) or hepatitis C virus (HCV), or
             active and infectious hepatitis B virus (HBV) infection.

         11. Pregnant or lactating.

         12. Evidence or history of central nervous system metastasis.

         13. Known hypersensitivity to any of the components of the study agent.

         14. Active or latent infection with Mycobacterium tuberculosis in any body tissue
             (especially renal and/or lung).

         15. Any other health condition that would preclude participation in the study in the
             judgment of the principal investigator.

        Part B: Second Remission

        Inclusion Criteria (Part B):

          1. Females ≥ 18 years of age at screening with a confirmed diagnosis of epithelial
             ovarian, fallopian tube, or peritoneal cancer.

          2. Underwent standard cytoreductive surgery and first-line chemotherapy containing
             platinum before first relapse and were in complete remission for at least 6 months
             prior to relapse.

          3. Relapsed once and then underwent standard platinum-based second-line chemotherapy (at
             least 3 cycles is required) with or without a second bulk-reducing surgery.

          4. Second remission defined as:

               1. No definitive evidence of disease (NED) on computed tomography (CT) or magnetic
                  resonance imaging (MRI) of the abdomen and pelvis;

               2. CA-125 ≤ upper limit of normal (ULN) or 90% reduction in CA-125 since start of
                  second-line chemotherapy;

               3. Negative physical exam (ie, no clinical signs).

          5. Life expectancy ≥ 3 months in the opinion of the investigator.

          6. Signed an informed consent form (ICF).

          7. Willing and able to complete study procedures within the expected study timelines.

          8. Mucin 1-positive tumor as determined by central immunohistopathology.

          9. Histologically documented EOC, fallopian tube, or peritoneal cancer (patients with
             pseudomyxoma, mesothelioma, unknown primary tumor, sarcoma, or neuroendocrine
             histology, with borderline ovarian cancer, ie, patients with low malignant potential
             tumors, and with clear cell or mucinous histology are excluded).

         10. Adequate end-organ and hematological function as defined by:

               1. Adequate bone marrow function: white blood cells (WBCs) ≥ 3.0 K/µL, absolute
                  neutrophil count (ANC) ≥ 1.5 × 109/L, hemoglobin ≥ 9 g/dL, and platelets ≥ 100 ×
                  109/L.

               2. Adequate renal function, defined as serum creatinine ≤ 1.5 × ULN.

               3. Adequate liver function, defined as serum glutamic oxaloacetic
                  transaminase/aspartate aminotransferase (SGOT/AST) and serum glutamic pyruvic
                  transaminase/alanine aminotransferase (SGPT/ALT) ≤ 2 × ULN and serum bilirubin ≤
                  1.5 × ULN.

         11. Generally well-controlled blood pressure with systolic blood pressure ≤ 140 mmHg and
             diastolic blood pressure ≤ 90 mmHg prior to randomization (antihypertensive
             medications are permitted). Low-dose chronic hormonal or steroidal treatments are also
             permitted.

         12. Not pregnant, and if of childbearing potential, agrees to use a highly effective
             method of birth control (implanted, injectable, or oral combination hormonal method
             alone or in possible combinations, intrauterine device, vasectomized partner, or
             abstinence) prior to study entry, for the duration of the study, and for 3 months
             after the last dose of study agent. Male partners of a study patient must use a condom
             in addition to the acceptable method of contraception for the female partner, as
             specified above.

         13. Eastern Cooperative Oncology Group (ECOG) status of 0 or 1 (applicable at the baseline
             visit only).

        Exclusion Criteria (Part B):

          1. More than 2 previous lines of chemotherapy for EOC, fallopian tube, or peritoneal
             cancer.

          2. Primary platinum-refractory or platinum-resistant disease (ie, patients who progress
             prior to cessation of induction therapy [platinum refractory] or recur within 6 months
             after cessation [platinum resistant]).

          3. Treatment with any investigational product (for any condition) within 4 weeks of
             screening. Enrolled in or has not completed at least 28 days of treatment (prior to
             screening) since ending another investigational device or drug treatment, or currently
             receiving other investigational treatments.

          4. Concurrent systemic treatment with steroids or other immunosuppressant agents at a
             dose considered by the investigator to be higher than a standard physiological dose.

          5. Evidence of severe or uncontrolled cardiac disease, including myocardial infarction or
             unstable angina within 6 months of screening, congestive heart failure, or ventricular
             arrhythmias requiring medication.

          6. Diagnosed immunodeficiency or autoimmune disorder.

          7. Infection with human immunodeficiency virus (HIV) or hepatitis C virus (HCV), or
             active and infectious hepatitis B virus (HBV) infection.

          8. Pregnant or lactating.

          9. Evidence or history of central nervous system metastasis.

         10. Known hypersensitivity to any of the components of the study agent.

         11. Any unresolved persistent toxicities from prior systemic therapy that are either Grade
             3 or Grade 4 (except alopecia) per the Common Terminology Criteria for Adverse Events
             (CTCAE) version 4.0.

         12. Intent to treat patient with both an anti-angiogenesis therapy (such as bevacizumab)
             and a poly (ADP-ribose) polymerase (PARP) inhibitor as part of maintenance therapy.
             Only one or the other are permitted while the patient is on study and must be started
             between the Baseline visit and Visit 1 (first treatment visit) if it will be used as
             part of the patient's maintenance therapy regimen.