Folate Receptor Alpha Peptide Vaccine With GM-CSF Versus GM-CSF Alone in Patients With Platinum Sensitive Ovarian Cancer

• ClinicalTrials.gov Identifier: NCT02978222
• Recruitment Status: Terminated
• First Posted: November 30, 2016
• Last Update Posted: February 20, 2020
• Sponsor: Marker Therapeutics, Inc.
• Information provided by (Responsible Party): Marker Therapeutics, Inc.

Tracking Information

• First Submitted Date: November 22, 2016
• First Posted Date: November 30, 2016
• Last Update Posted Date: February 20, 2020
• Actual Study Start Date: January 26, 2017
• Actual Primary Completion Date: January 15, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 28, 2016)

Progression free survival [ Time Frame: 2 years ]

Time to disease progression or recurrence of ovarian cancer defined as disease progression by RECIST 1.1., disease recurrence, death without progression or CA125 progression

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 24, 2017)

• Overall survival (OS) [ Time Frame: 2 years ]
  Death with or without ovarian cancer progression
• Best overall response rate [ Time Frame: 2 years ]
  Best overall response defined as sum of Complete Responses and Partial Responses in the subset of patients with measurable tumor lesions at baseline
• Disease control rate [ Time Frame: 2 years ]
  Disease control rate defined as the sum of Complete Responses, Partial Responses and Stable Disease
• Response Rate by immune-related RECIST (irRECIST) criteria [ Time Frame: 2years ]
• Cancer Antigen (CA)-125 response [ Time Frame: 2years ]
  2 fold increase from from the baseline CA125 (if above normal at baseline) or 2-fold greater than normal limits (if within normal limits at baseline)

Original Secondary Outcome Measures (submitted: November 28, 2016)

• Overall survival (OS) [ Time Frame: 2 years ]
  Death with or without ovarian cancer progression
• Best overall response [ Time Frame: 2 years ]
  Best overall response defined as sum of Complete Responses and Partial Responses in the subset of patients with measurable tumor lesions at baseline
• Disease control rate [ Time Frame: 2 years ]
  Disease control rate defined as the sum of Complete Responses, Partial Responses and Stable Disease
• Response Rate by immune-related RECIST (irRECIST) criteria [ Time Frame: 2years ]
• Cancer Antigen (CA)-125 response [ Time Frame: 2years ]
  2 fold increase from from the baseline CA125 (if above normal at baseline) or 2-fold greater than normal limits (if within normal limits at baseline)

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Folate Receptor Alpha Peptide Vaccine With GM-CSF Versus GM-CSF Alone in Patients With Platinum Sensitive Ovarian Cancer
• Official Title: A Randomized Multicenter Phase II Trial to Evaluate the Safety, Efficacy and Immunogenicity of Vaccination With Folate Receptor Alpha Peptides With GM-CSF Versus GM-CSF Alone in Patients With Platinum Sensitive Ovarian Cancer and a Response or Stable Disease to Platinum Therapy
• Brief 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.

Detailed Description

This is a multicenter double-blind controlled randomized Phase II study to evaluate the activity of folate receptor alpha (FRα) peptide vaccine as a consolidation treatment following completion of no less than 4 cycles of a platinum containing regimen in patients with platinum-sensitive, non-mucinous ovarian, fallopian tube or primary peritoneal cancer.

The patients will have demonstrated a tumor response or stable disease upon their last regimen (per RECIST v1.1 and/or CA125 GCIG criteria) prior to enrolment in this study.

Following randomization, patients will be administered TPIV200 with GM-CSF adjuvant or GM-CSF control alone. Patients will have booster doses and tumor assessments done every 12 weeks ± 1 week for up to 1.5 years, until objective disease progression or the patient withdraws consent. Tumor responses will be assessed at the study sites by evaluating tumor images/scans according to RECIST v1.1.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Platinum Sensitive Ovarian Cancer
• Ovarian Cancer

Intervention

• Biological: FRα peptide plus Adjuvant (GM-CSF)
  Intradermal injection FRα peptides, 500μg each - plus GM-CSF 125 μg
  Other Name: TPIV200 with GM-CSF adjuvant
• Drug: Adjuvant (GM-CSF) Alone
  Intradermal injection 125 μg GM-CSF
  Other Name: Leukine®

Study Arms

• Experimental: FRα peptide plus adjuvant (GM-CSF)
  FRα peptide vaccine with GM-CSF adjuvant ID administration monthly for 6 months followed by booster administrations every 3 months for up to 1.5 years
  Intervention: Biological: FRα peptide plus Adjuvant (GM-CSF)
• Placebo Comparator: Adjuvant (GM-CSF) Alone
  GM-CSF adjuvant alone ID administration monthly for 6 months followed by booster administrations every 3 months for up to 1.5 years
  Intervention: Drug: Adjuvant (GM-CSF) Alone

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: May 9, 2017): 120
• Original Estimated Enrollment (submitted: November 28, 2016): 80
• Actual Study Completion Date: January 15, 2020
• Actual Primary Completion Date: January 15, 2020 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02978222
• Other Study ID Numbers: FRV-004
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Marker Therapeutics, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Marker Therapeutics, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Richard Kenney, MD; Marker Therapeutics, Inc.

• PRS Account: Marker Therapeutics, Inc.
• Verification Date: February 2020