Window of Opportunity Trial of Durvalumab (MEDI4736) or Durvalumab/Tremelimumab as Neoadjuvant Chemotherapy to Identify Immune Dynamics in Surgically Resectable Head and Neck Cancer Patients.
Overview
- Phase
- Phase 2
- Intervention
- Durvalumab
- Conditions
- Stage II-IVB Operable HNSCC Oral Cavity
- Sponsor
- Yonsei University
- Enrollment
- 48
- Locations
- 1
- Primary Endpoint
- locoregional relapse rate
- Status
- Active, not recruiting
- Last Updated
- 3 years ago
Overview
Brief Summary
This is a phase II randomized, open label study of durvalumab with/ without tremelimumab as neoadjuvant therapy and durvalumab maintenance after SoC RTx with/without cisplatin as post-surgical adjuvant therapy in treatment naïve participants with newly diagnosed resectable LA HNSCC. The study will be conducted in conformance with Good Clinical Practices (GCP). Approximately 44 participants will be randomized in a 1:1 ratio to below two Arms
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically confirmed surgically resectable HNSCC oral cavity, hypopharynx, oropharynx, and larynx
- •Measurable disease defined as lesions that can be accurately measured by RECIST 1.
- •Written informed consent and any locally-required authorization obtained from the patient prior to performing any protocol-related procedures, including screening evaluations
- •Age \>18 years at time of study entry or Adult male or female
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Body weight \>30kg
- •Life expectancy of at least 12 weeks
- •Adequate normal organ and marrow function as defined below:
- •Haemoglobin ≥9.0 g/dL
- •Absolute neutrophil count (ANC) \> 1500 per mm3
Exclusion Criteria
- •Involvement in the planning and/or conduct of the study Participation in another clinical study with an investigational product during the last Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study 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.
- •History of allogenic organ transplantation. 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 or tremelimumab may be included only after consultation with the Study Physician.
- •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.
- •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
Arms & Interventions
Durvalumab monotherapy Arm
Patients in the durvalumab (MEDI4736) monotherapy treatment group will receive durvalumab (MEDI4736) (1500mg Q4W) once prior to surgery in this study. After surgical resection, these patients will receive the post op adjuvant treatment including RTx with/without cisplatin based on the pathologic findings and physician's discretion. After completion of adjuvant treatment, durvalumab (MEDI4736) 1500mg Q4W as maintenance treatment for up to a maximum of 12 months until confirmed disease progression unless there is unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met. The first durvalumab (MEDI4736) monotherapy dose at 1500mg Q4W will be within 8 weeks after the completion of adjuvant therapy. If a patient's weight falls to 30kg or below the patient should receive weight-based dosing equivalent to 20 mg/kg of durvalumab Q4W until the weight improves to \>30 kg, at which point the patient should start receiving the fixed dosing of durvalumab 1500mg.
Intervention: Durvalumab
Durvalumab + tremelimumab combination therapy Arm
Patients in the durvalumab (MEDI4736) + tremelimumab combination therapy treatment group will receive durvalumab (MEDI4736) (1500mg Q4W) in combination with tremelimumab (75 mg IV Q4W) once prior to surgery in this study. After surgical resection, these patients will receive the post op adjuvant treatment including RTx with/without cisplatin based on the pathologic findings and physician's discretion. After completion of adjuvant treatment, durvalumab (MEDI4736) 1500mg Q4W as maintenance treatment for up to a maximum of 12 months until confirmed disease progression unless there is unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met. The first durvalumab (MEDI4736) monotherapy dose at 1500mg Q4W will be within 8 weeks after the completion of adjuvant therapy.
Intervention: durvalumab + tremelimumab
Outcomes
Primary Outcomes
locoregional relapse rate
Time Frame: every 3 months, assessed up to 2 years
investigate the locoregional relapse rate (LRR)
Distant metastatic rate
Time Frame: every 3 months, assessed up to 2 years
Distant metastatic rate
Secondary Outcomes
- distant metastases free survival (DMFS)(every 3 months, assessed up to 2 years)
- locoregional control (LRC) time(every 3 months, assessed up to 2 years)
- progression-free survival (PFS)(every 3 months, assessed up to 2 years)