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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Platinum Sensitive Ovarian Cancer, Ovarian Cancer

Intervention / Treatment
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* Biological: FRα peptide plus Adjuvant (GM-CSF)
* Drug: Adjuvant (GM-CSF) Alone


Participation Criteria
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Eligibility Criteria
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Criteria for Inclusion: Female patient ≥ 18 years Willing and able to give informed consent 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. 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. 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. 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 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. 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. 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 Life expectancy > 24 weeks ECOG performance status of 0 or 1 Formalin fixed, paraffin embedded tumor sample from the primary cancer must be sent for central testing. Criteria for Exclusion Histology consistent with non-serous, non-endometrioid (i.e. mucinous or clear cell), or low-grade or borderline serous ovarian carcinoma Patients with 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) < 28 days prior to the first dose of study drug. 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 subject to give written informed consent Symptomatic thyroid disease, unless negative for thyroid antibodies (TSH receptor, TPO, thyroglobulin). Subjects who are pregnant or are breast feeding. 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. Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results Symptomatic or uncontrolled brain metastasis requiring concurrent treatment, inclusive of but not limited to surgery, radiation and/or corticosteroids Subject with uncontrolled seizures

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FRα peptide plus adjuvant (GM-CSF)<br>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 | Biological: FRα peptide plus Adjuvant (GM-CSF)<br>* Intradermal injection FRα peptides, 500μg each - plus GM-CSF 125 μg<br>* Other names: TPIV200 with GM-CSF adjuvant;|
| Placebo Comparator: Adjuvant (GM-CSF) Alone<br>GM-CSF adjuvant alone ID administration monthly for 6 months followed by booster administrations every 3 months for up to 1.5 years | Drug: Adjuvant (GM-CSF) Alone<br>* Intradermal injection 125 μg GM-CSF<br>* Other names: Leukine®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | Death with or without ovarian cancer progression | 2 years | 
| 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 | 
| 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 |