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

Ovarian Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02978222
• Other study ID #: FRV-004
• Status: Terminated
• Phase: Phase 2
• Start date: July 20, 2017
• Est. completion date: January 15, 2020

Study information

• Verified date: February 2020
• Source: Marker Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 120
• Est. completion date: January 15, 2020
• Est. primary completion date: January 15, 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Hypersensitivity
• Ovarian Cancer
• Ovarian Neoplasms
• Platinum Sensitive Ovarian Cancer

Intervention

Biological:
• FRa peptide plus Adjuvant (GM-CSF)
Intradermal injection FRa peptides, 500µg each - plus GM-CSF 125 µg

Drug:
• Adjuvant (GM-CSF) Alone
Intradermal injection 125 µg GM-CSF

Locations

Country	Name	City	State
United States	Abington Memorial Hospital	Abington	Pennsylvania
United States	University Of New Mexico Comprehensive Cancer Center	Albuquerque	New Mexico
United States	UAB Gynecology Oncology	Birmingham	Alabama
United States	Duke University Medical Center	Durham	North Carolina
United States	Research Partners	Jackson	Mississippi
United States	Mayo Clinic Florida	Jacksonville	Florida
United States	MidAmerica Division, Inc. c/o Research Medical Center	Kansas City	Missouri
United States	Mt. Sinai Comprehensive Cancer Center	Miami Beach	Florida
United States	Tennessee Oncology/Sarah Cannon Research Institute	Nashville	Tennessee
United States	Hematology/Oncology Lenox Hill Hospital	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Women's Cancer Research Foundation	Newport Beach	California
United States	Mayo Clinic Cancer Center	Phoenix	Arizona
United States	OHSU	Portland	Oregon
United States	Mayo Clinic Rochester	Rochester	Minnesota
United States	The Stamford Hospital/Bennett Cancer Center	Stamford	Connecticut
United States	Moffitt Cancer Center	Tampa	Florida
United States	Florida Cancer Specialist	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Marker Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival	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	2 years
Secondary	Overall Survival (OS)	Death with or without ovarian cancer progression	2 years
Secondary	Best Overall Response Rate	Best overall response defined as sum of Complete Responses and Partial Responses in the subset of patients with measurable tumor lesions at baseline.; Best overall response is a binary endpoint and defined as a best overall response of either CR or PR among subjects with measurable lesions at baseline, using RECIST v1.1.; Disease control rate is the percentage of subjects with a response of CR, PR, or SD or non-CR/non-PR vs PD among subjects with measurable lesions at baseline.	2 years
Secondary	Disease Control Rate	Disease control rate defined as the sum of Complete Responses, Partial Responses and Stable Disease.; Best overall response is a binary endpoint and defined as a best overall response of either CR or PR among subjects with measurable lesions at baseline, using RECIST v1.1.; Disease control rate is the percentage of subjects with a response of CR, PR, or SD or non-CR/non-PR vs PD among subjects with measurable lesions at baseline.	2 years