Folate Receptor Alpha Peptide Vaccine With GM-CSF Versus GM-CSF Alone in Patients With Platinum Sensitive Ovarian Cancer
Condition: Platinum Sensitive Ovarian Cancer; Ovarian Cancer
MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Hypersensitivity
Intervention: FRα peptide plus Adjuvant (GM-CSF); Adjuvant (GM-CSF) Alone
Intervention description: Intradermal injection FRα peptides, 500μg each - plus GM-CSF 125 μg; Intradermal injection 125 μg GM-CSF
Intervention MeSH terms: Molgramostim; Sargramostim
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 120.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a double-blind, randomized, parallel groups Phase II trial. Patients with
      platinum-sensitive advanced ovarian cancer, defined as a lack of progression by RECIST v1.1
      criteria following completion of standard-of-care chemotherapy, including a minimum of 4
      cycles of a platinum-containing regimen. Patients will be randomized to either the vaccine
      regimen with GM-CSF adjuvant or GM-CSF adjuvant alone as a control group. Treatment will be
      administered as a consolidation therapy within one year of the last administration of
      platinum, targeting the first remission.
    

Eligibility criteria:

        Criteria for Inclusion:

          1. Female patient ≥ 18 years

          2. Willing and able to give informed consent

          3. Stage III-IV platinum-sensitive (defined as a lack of progression by RECIST v1.1
             criteria following completion of standard-of-care chemotherapy, including a minimum of
             4 cycles of a platinum-containing regimen) epithelial ovarian, fallopian tube or
             primary peritoneal carcinoma in first remission.

          4. Histologic documentation of diagnosis of carcinoma is required and the following
             histologic subtypes are eligible: high grade (grade ≥3+) serous or endometrioid
             carcinoma, carcinosarcoma, or poorly-differentiated adenocarcinoma, or mixed
             (including above subtypes only). Note that synchronous serous or endometrioid uterine
             or fallopian cancers are allowed.

          5. The patient must have demonstrated an objective response (PR or CR) or stable disease
             (SD) with the last chemotherapy prior to enrollment and this response must be stable
             (without progressive disease) before randomization.

          6. Patients must receive their first dose of vaccine within 1 year of completion of their
             final dose of a chemotherapeutic agent of the platinum-containing regimen

          7. Adequate normal organ and marrow function within 14 days prior to first vaccine
             administration:

               -  Absolute neutrophil count > 1.5 x 109/L

               -  Platelet > 100 x 109/L

               -  Hemoglobin > 9.0 g/dL

               -  Serum bilirubin < 1.5 times ULN (unless Gilbert's syndrome without concurrent
                  clinically significant liver disease

               -  AST/ALT < 2.5 ULN unless liver metastasis in which case it must be < 5 x ULN

               -  Serum creatinine CL > 40 mL/min by Cockcroft-Gault formula.

          8. Anti-nuclear antibody (ANA) negative or low-positive institutional range, as
             determined within 28 days from registration. Intermediate values (usually defined by a
             titer of ≤1:80, or as indicated by institutional range) are acceptable if there are,
             in the opinion of the Investigator, no early signs of an autoimmune disease.

          9. Female subjects must either be of non-reproductive potential (i.e. post-menopause by
             history: > 60 years old and no menses for > 12 months naturally or secondary to
             radiation/chemotherapy; OR serum FSH, LH and estradiol levels in the post-menopausal
             range; OR history of hysterectomy; OR history of bilateral tubal ligation; OR history
             of bilateral oophorectomy), or must have a negative serum pregnancy test upon study
             entry

         10. Life expectancy > 24 weeks

         11. ECOG performance status of 0 or 1

         12. Formalin fixed, paraffin embedded tumor sample from the primary cancer must be sent
             for central testing.

        Criteria for Exclusion

          1. Histology consistent with non-serous, non-endometrioid (i.e. mucinous or clear cell),
             or low-grade or borderline serous ovarian carcinoma

          2. Patients with a history of other cancers (other than non-melanoma skin cancers [i.e.
             basal or squamous cell]) within the past 3 years.

          3. Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, targeted
             therapy, biological/cell therapy, tumor embolization, monoclonal antibodies, other
             investigational agent) < 28 days prior to the first dose of study drug.

          4. Current or prior use of immunosuppressive medication within 28 days prior to the fist
             dose of study drug with the exception of topical, intranasal or inhaled
             corticosteroids or systemic corticosteroids at physiological doses, which are not to
             exceed 10 mg/day of prednisone, or an equivalent corticosteroid.

          5. Active autoimmune disease requiring therapy within the past 2 years. Note: patients
             with vitiligo, Grave's disease or psoriasis not requiring systemic treatment within
             the past 2 years are not excluded.

          6. History of hypersensitivity to GM-CSF

          7. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
             angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active
             bleeding diatheses including any subject known to have evidence of acute or chronic
             hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric
             illness/social situations that would limit compliance with study requirements or
             compromise the ability of the subject to give written informed consent

          8. Symptomatic thyroid disease, unless negative for thyroid antibodies (TSH receptor,
             TPO, thyroglobulin).

          9. Subjects who are pregnant or are breast feeding.

         10. Subjects who or of reproductive potential, and are either:

               -  Not abstinent;

               -  Not in an exclusive relationship with a partner who is surgically sterile;

               -  Not employing an effective method of birth control.

         11. Any condition that, in the opinion of the investigator, would interfere with
             evaluation of study treatment or interpretation of patient safety or study results

         12. Symptomatic or uncontrolled brain metastasis requiring concurrent treatment, inclusive
             of but not limited to surgery, radiation and/or corticosteroids

         13. Subject with uncontrolled seizures