An Open Label, Single Arm, Safety Lead-in, Multicenter, Investigator Initiated Trial of Combination of Durvalumab , An Immune Checkpoint Inhibitor, and BVAC-C, A Cell-based Immunotherapeutic Vaccine, in Patients With HPV 16 or 18 Positive Cervical Cancer Failure to First-Line Platinum-based Chemotherapy
Overview
- Phase
- Phase 2
- Intervention
- Not specified
- Conditions
- Cervical Cancer
- Sponsor
- Samsung Medical Center
- Enrollment
- 37
- Primary Endpoint
- Part B : Evaluate the safety and clinical efficacy, as measured by 6-month PFS rate
- Status
- Not yet recruiting
- Last Updated
- 5 years ago
Overview
Brief Summary
This is an exploratory, open label, multi-center trial to evaluate the safety and efficacy of combination of durvalumab with BVAC-C in patients with cervical cancer refractory to or relapse after platinum-based first-line chemotherapy with safety lead-in phase.
The study consists of 2 parts: part A, a safety lead-in phase, and part B, an exploratory safety and efficacy evaluation phase.
Part A will be conducted as a 3+3 dose escalation manner, and part B will be conducted as a non-randomized single arm study.
•Part A: Open-labeled; 3+3 dose-escalation; Multi-center; safety lead-in phase
•Part B: Open-labeled; Non-randomized, Single arm; Multi-center, efficacy evaluation phase
Investigators
Eligibility Criteria
Inclusion Criteria
- •Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations
- •Willing and ability to provide blood and tumor tissue samples
- •Histologically confirmed HPV 16/18-positive cervical carcinoma (squamous cell carcinoma; adenocarcinoma, adenosquamous carcinoma)
- •Prior primary therapy with radical surgery, radical surgery followed by radiotherapy (+/- chemo), chemotherapy, or primary concurrent chemoradiotherapy
- •Cervical cancer recurrent after or refractory to only 1 prior first-line platinum-based chemotherapy +/- bevacizumab.Measurable disease per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1)
- •Eastern Cooperative Oncology Group performance status of 0-1
- •Must have a life expectancy of at least 12 weeks
- •Age \> 18 years at time of study entry
- •Body weight \>30 kg
- •Adequate normal organ and marrow function as defined below:
Exclusion Criteria
- •Participation in another clinical study with an investigational product during the last 4 weeks
- •Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
- •Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies) 4 weeks prior to the first dose of study drug
- •Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria
- •Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
- •Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Study Physician.
- •Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
- •Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug
- •Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.
- •History of allogenic organ transplantation.
Outcomes
Primary Outcomes
Part B : Evaluate the safety and clinical efficacy, as measured by 6-month PFS rate
Time Frame: 6 Months
The primary objective of the part B is to evaluate the safety and clinical efficacy, as measured by 6-month PFS rate, of the combination therapy of durvalumab and BVAC-C in patients with HPV 16 or 18 positive cervical cancer recurrent after or refractory to first-line platinum-based chemotherapy +/-bevacizumab.
Part A : Dose-limiting toxicities(DLTs)
Time Frame: up to 11 weeks
The primary objective of the part A is to assess the maximum tolerable dose of BVAC-C combined with durvalumab 1500 mg as defined by dose-limiting toxicities (DLTs), and to find the maximum tolerated dose (MTD) that can be safely used for Part B (single arm phase II).
Secondary Outcomes
- Progression free survival (PFS) rate(12~24 Months)
- Overall survival (OS) rate(12~24 Months)
- Adverse event(AE)(up to 99 weeks)
- Disease control rate(DCR)(12~24 Months)
- Adverse events rate of special interest(AESI)(up to 99 weeks)
- Best overall response rate(BORR)(12~24 Months)