Adjuvant Therapeutic Cancer Vaccine (AST-201, pUMVC3-hIGFBP-2) in Patients With Advanced Ovarian Cancer

Study Overview
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Brief Summary
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The purpose of this phase 2 study is to assess the efficacy and safety for adjuvant therapeutic cancer vaccine AST-201 (pUMVC3-hIGFBP-2) in patients with newly diagnosed homologous-recombination proficient(HRP) advanced ovarian cancer (Stage III) after debulking surgery. Patients will receive AST-201 with rhuGM-CSF(Colony Stimulating Factor) or placebo with rhuGM-CSF in combination with standard adjuvant chemotherapy(Paclitaxel/Carboplatin).

Detailed Description
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The study will comprise a screening period of -28 Days prior to initiation of study treatment (Day 1); an enrollment period of 24 months; the treatment duration will be approximately of 5 months. The study will evaluate whether the addition of AST-201/rhuGM-CSF to the standard adjuvant chemotherapy will extend the Progression Free Survival(PFS) rate. Survival follow-up will be performed every 3 months (±14 days) after the End of treatment (EOT) visit for 2 years after randomization and every 6 months (±28 days) thereafter until disease progression or death from any cause or withdrawal of consent whichever comes first. Survival follow-up visits will be conducted by telephone, in-person visit, or chart review. The end of study (EOS) is defined as 2 years after the date of last patient enrollment.

Official Title
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A Randomized Phase 2 Study to Evaluate the Efficacy and Safety for Adjuvant Therapeutic Cancer Vaccine (AST-201, pUMVC3-hIGFBP-2) in Patients With Advanced Ovarian Cancer (Cornerstone-004)

Conditions
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Advanced Ovarian Cancer

Intervention / Treatment
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* Biological: AST-201
* Drug: Paclitaxel
* Drug: Carboplatin
* Drug: Placebo
* Drug: rhuGM-CSF(Granulocyte-Macrophage Colony-Stimulating Factor)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Newly diagnosed stage III (FIGO classification) epithelial ovarian cancer including primary peritoneal cancer, fallopian-tube cancer Has received upfront surgery and optimally debulked(a residual tumor less than 1 cm) Can start adjuvant therapy within 6 weeks of debulking surgery Has Homologous Recombination Proficiency (HRP) tumor defined by FDA-approved testing Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Demonstrates adequate organ function. Exclusion Criteria: Has a history of hypersensitivity or other contraindications to rhuGM-CSF Has a history of active malignancy ≤5 years prior to first administration of investigational drug except for adequately treated non-melanoma skin cancer or epithelial carcinoma without evidence of disease Is on immune suppression therapy or has a history of immune suppression therapy ≤4 weeks prior to the first administration of investigational drugs Has active or prior autoimmune disease or inflammatory disease Has active infectious disease including tuberculosis, hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infection Is pregnant or breastfeeding or expecting to conceive children within the projected duration of the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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
Interventional Model Description: Single blind, randomized, placebo-controlled, multicenter, phase 2 clinical study
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AST-301<br>AST-201 with rhuGM-CSF (3-week interval, 3 cycles in total) Standard chemotherapy (paclitaxel/carboplatin) (3-week interval, 6 cycles in total) * Both AST-201/rhuGM-CSF or Placebo/rhuGM-CSF will be given intradermally 2 weeks after each combination chemotherapy (on Day 15 of each cycle) for 3 cycles | Biological: AST-201<br>* i.d. (3-week interval, 3 cycles in total)<br>* Other names: pUMVC3-hIGFBP-2 multi-epitope plasmid DNA vaccine;Drug: Paclitaxel<br>* 3-week interval, 6 cycles in total<br>* Other names: Taxol;Drug: Carboplatin<br>* 3-week interval, 6 cycles in total<br>* Other names: Paraplatin;Drug: rhuGM-CSF(Granulocyte-Macrophage Colony-Stimulating Factor)<br>* i.d. (3-week interval, 3 cycles in total)<br>* Other names: Leukine;|
| Placebo Comparator: Placebo<br>Placebo with rhuGM-CSF (3-week interval, 3 cycles in total) Standard chemotherapy (paclitaxel/carboplatin) (3-week interval, 6 cycles in total) *Both AST-201/rhuGM-CSF or Placebo/rhuGM-CSF will be given intradermally 2 weeks after each combination chemotherapy (on Day 15 of each cycle) for 3 cycles | Drug: Paclitaxel<br>* 3-week interval, 6 cycles in total<br>* Other names: Taxol;Drug: Carboplatin<br>* 3-week interval, 6 cycles in total<br>* Other names: Paraplatin;Drug: Placebo<br>* i.d. (3-week interval, 3 cycles in total)<br>* Other names: Normal saline (USP);Drug: rhuGM-CSF(Granulocyte-Macrophage Colony-Stimulating Factor)<br>* i.d. (3-week interval, 3 cycles in total)<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 (PFS) | the time from the date of randomization to disease progression, or death from any cause whichever occurs first | overall study duration (approximately 48 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2-year PFS rate | proportion of patients alive without disease progression or death at two years after the randomization | 24months from the first dose of AST-301 administration | 
| Overall Survival (OS) | the time from the date of randomization to death from any cause | overall study duration (approximately 48 months) | 
| AST-201 specific immunogenicity by Interferon gamma (IFN-gamma) enzyme-linked immunospot (ELISpot ) | AST-201 specific IFN-gamma ELISpot | 17months | 
| Number of participants with Adverse events as graded by the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] version 5.0) | Adverse events (AEs) Treatment-emergent adverse events (TEAEs) Serious adverse events (SAEs) Vital signs Physical examination Eastern Cooperative Oncology Group (ECOG) performance status Electrocardiogram (ECG) test Laboratory tests | 5 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cancer vaccine, phase 2 study, Advanced ovarian cancer, homologous-recombination proficient (HRP)