Combination of Durvalumab and BVAC-C in Patients With HPV 16 or 18 Positive Cervical Cancer Failure to First-Line Platinum-based Chemotherapy

NCT04800978 | Unknown Phase 2

• 1 other identifier: ESR-18-14325
• Study Type: interventional
• Target: 37
• Locations: 0 countries
• Sites: N/A

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

Conditions

Cervical Cancer

Keywords

BVAC-C; Durvalumab; Cervical cancer

Outcome Measures

Primary Outcomes (2)

• Part A : Dose-limiting toxicities(DLTs)

  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).

  up to 11 weeks

• Part B : Evaluate the safety and clinical efficacy, as measured by 6-month PFS rate

  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.

  6 Months

Secondary Outcomes (6)

• Best overall response rate(BORR)

  12~24 Months

• Disease control rate(DCR)

  12~24 Months

• Progression free survival (PFS) rate

  12~24 Months

• Overall survival (OS) rate

  12~24 Months

• Adverse event(AE)

  up to 99 weeks

Other Outcomes (7)

• Programmed death-ligand 1(PD-L1)

  1-2 day

• Tumor mutational burden(TMB)

  1-2 day

• Rate of Tumor infiltrating lymphocytes(TIL)

  1-2 day

Study Arms (1)

BVAC-C+Durvalumab

EXPERIMENTAL

• Part A: 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). • Part B: 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.

Biological: BAVC-C+Durvalumab

Interventions

BAVC-C+Durvalumab BIOLOGICAL

* Durvalumab Durvalumab will be supplied in glass vials containing 500 mg of liquid solution at a concentration of 50 mg/mL for infusion after dilution. * BVAC-C BVAC-C will be supplied in cyclic olefin co-polymer vials containing 1x10⁸ cells of suspension at a concentration of 5x10⁷ cells/mL infusion

BVAC-C+Durvalumab

Eligibility Criteria

• Age: 19 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Haemoglobin ≥9.0 g/dL (Note: The use of transfusion or other intervention to achieve Hgb ≥ 9.0 g/dl is acceptable)
• Absolute neutrophil count (ANC) \> 1.5x10³per mm³
• Platelet count ≥75x10⁹/L (≥75,000 per mm³)
• Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert's syndrome, who will be allowed only in consultation with their physician.
• AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤5x ULN

You may not qualify if:

• 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
• 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.
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). The following are exceptions to this criterion:
• Patients with vitiligo or alopecia
• Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
• Any chronic skin condition that does not require systemic therapy
• Patients without active disease in the last 5 years may be included but only after consultation with the study physician
• Patients with celiac disease controlled by diet alone

Sponsors & Collaborators

• Samsung Medical Center: lead
• Asan Medical Center: collaborator
• Seoul National University Hospital: collaborator
• Seoul National University Bundang Hospital: collaborator
• Severance Hospital: collaborator
• National Cancer Center, Korea: collaborator

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Central Study Contacts

ByoungGie Kim

CONTACT

+82-02-3410-3513; bgkim@skku.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: •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

Study Record Dates

• First Submitted: January 11, 2021
• First Posted: March 16, 2021
• Study Start: June 14, 2021
• Primary Completion: August 31, 2024
• Study Completion: August 31, 2024
• Last Updated: March 16, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share