Clinical Trial 18983

Cancer Type: Gynecological Tumor
Interventions:FR alpha peptide vaccine; GM-CSF; Leukine (GM-CSF); sargramostatin (GM-CSF)

Study Type: Treatment
Phase of Study: Phase II
Investigators:

  • Robert Wenham

Overview

Study Title

A Randomized Multicenter Phase II Trial To Evaluate The Safety, Efficacy And Immunogenicity Of Vaccination With Folate Receptor Alpha Peptides Admixed With GM-CSF As A Vaccine Adjuvant Versus GM-CSF Alone In Patients With Platinum Sensitive Ovarian Cancer And A Response Or Stable Disease To Platinum Therapy

Summary

The goal of the study vaccine is to help the participant's body recognize ovarian cancer and keep it from coming back. It does this by targeting a protein (called folate receptor alpha) that is rare in healthy tissue but is common in ovarian cancer tissue. The study vaccine is made from protein pieces that are found on ovarian and breast cancers. To enhance the study vaccine, the protein pieces are mixed with what is called an adjuvant, which alerts the immune system. For this study, the adjuvant called granulocyte-macrophage colony stimulating factor (GM-CSF) will be mixed with the study vaccine prior to administration. The purpose of the study is to compare Folate receptor alpha (protein) and GM-CSF (adjuvant) to GM-CSF alone.

Objective

Primary Objectives: To determine the efficacy of hu-FRá peptide vaccine with GM-CSF immune adjuvant compared to GM-CSF alone assessed by progression-free survival (PFS) by RECIST. To evaluate the safety and tolerability of hu-FRá peptide vaccine with GM-CSF versus GM-CSF alone. Secondary Objectives: To determine the efficacy of hu-FRá peptide vaccine with GM-CSF immune adjuvant compared to immune adjuvant alone by assessment of: - Overall survival (OS), - Best overall response (CR+PR), and duration of response (DOR). - Disease control rate (CR+PR+SD). - Response Rate by irRECIST criteria. - Cancer Antigen (CA)-125 response (Gynecologic Cancer InterGroup [GCIG] criteria).

Inclusion Criteria

  • Female patient ≥ 18 years
  • Willing and able to give informed consent
  • Stage III-IV platinum-sensitive (defined as a lack of progression by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 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.
  • 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.
  • Must have demonstrated an objective response (partial response (PR) or complete response (CR)) or stable disease (SD) with the last chemotherapy prior to enrollment and this response must be stable (without progressive disease) before randomization.
  • Participants 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
  • Adequate normal organ and marrow function within 14 days prior to first vaccine administration
  • 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.
  • Females must either be of non-reproductive potential or must have a negative serum pregnancy test upon study entry
  • Life expectancy > 24 weeks
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Formalin fixed, paraffin embedded tumor sample from the primary cancer must be sent for central testing.

  • Exclusion Criteria

  • Histology consistent with non-serous, non-endometrioid (i.e., mucinous or clear cell), or low-grade or borderline serous ovarian carcinoma
  • A history of other cancers (other than non-melanoma skin cancers [i.e., basal or squamous cell]) within the past 3 years.
  • Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, targeted therapy, biological/cell therapy, tumor embolization, monoclonal antibodies, other investigational agent) > 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.
  • 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.
  • History of hypersensitivity to GM-CSF
  • 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 participant to give written informed consent
  • Symptomatic thyroid disease, unless negative for thyroid antibodies (TSH receptor, TPO, thyroglobulin).
  • Are pregnant or breast feeding.
  • Participants of reproductive potential who will not follow effective birth control guidelines.
  • Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of participant safety or study results
  • Symptomatic or uncontrolled brain metastasis requiring concurrent treatment, inclusive of but not limited to surgery, radiation and/or corticosteroids
  • Have uncontrolled seizures