Head and Neck Neoplasms, HNSCC
Conditions
Keywords
biomarker driven umbrella trial, Durvalumab + Tremelimumab Combination Treatment
Brief summary
Phase II study of Durvalumab+/- Tremelimumab in patients with recurred metastatic head and neck squamous cell carcinoma
Detailed description
Open, multicenter, single arm, phase II, biomarker driven umbrella trial for head and neck squamous cell carcinoma
Interventions
Durvalumab: 1.5g Q4W plusTremelimumab: 75mg Q4W up to 4cycle then Durvalumab 750mg Q2W, till PD or unacceptable toxicity.
Sponsors
Korean Cancer Study Group
Seoul National University Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 1\. Recurrent or metastatic HNSCC, regardless of PD-L1 or HPV status 2. Age ≥20 3. ECOG PS 0-1 4. Ineligibility for local therapy (surgery or radiotherapy) 5. Prior palliative chemotherapy including platinum-based chemotherapy. When recurred within 6 months of definitive/neoadjuvant/adjuvant chemo- or chemoradiation, the chemotherapy is considered a line of therapy 6. At least one measurable lesion by RECIST ver 1.1 7. Adequate organ function for treatment * Absolute neutrophil count (ANC) ≥1000 cells/mm3 * Hemoglobin: ≥ 9.0 g/dL * Platelets ≥100,000 cells/mm3 * Estimated creatinine clearance ≥40 mL/min, or serum creatinine \<1.5 x institution upper limit of normal * Bilirubin ≤1.5 x upper limit of normal (ULN) * AST (SGOT) ≤2.5 x ULN (5.0 x ULN if hepatic metastases) * ALT (SGPT) ≤2.5 x ULN (5.0 x ULN if hepatic metastases) 8. 12-Lead electrocardiogram (ECG) with normal tracing or non-clinically significant changes that do not require medical intervention 9. The patient has provided signed informed consent
Exclusion criteria
* 1\. Previous treatment with PD-1 or PDL-1 inhibitors 2. Nasopharyngeal carcinoma 3. Cytotoxic chemotherapy within 3 weeks of study entry; immunotherapy or investigational drug within 5 half-lives of study entry 4. Any major operation or irradiation within 4 weeks of baseline disease assessment. Palliative radiation is allowed 5. Symptomatic brain metastasis 6. Patients with known interstitial lung disease 7. Patients with uncontrolled or significant cardiovascular disease 8. Previous or concurrent malignancy (except for basal or squamous cell skin cancer and/or in situ carcinoma of the cervix, thyroid cancer treated curatively) without evidence of recurrence for at least 3 years prior to study entry. 9\. Pregnant or breast-feeding women 10. Systemic immunosuppressive therapy 11. Active autoimmune disease 12. Patient who have an active systemic fungal and/or known viral infection (for example, human immunodeficiency virus antibodies, hepatitis B surface antigen, or hepatitis C antibodies) (inactive HBV carrier with adequate prophylactic antiviral agent can be enrolled) 13. Body weight \<30kg 14\. Other severe acute or chronic medical condition or laboratory abnormality that may increase the risk associated with trial participation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response rate (RR) | 24months | RECIST1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| •Progression-Free Survival (PFS) | 24months | Disease progression is assessed by RECIST 1.1. |
| •Overall Survival (OS) | 24months | Overall Survival is defined as the time from first dose to death due to any cause. Through the follow-up within 30 days after study completion or termination of the last subject, death and date of death will be checked for subject alive during treatment period |
| •Toxicity | 24months | number of patients with treatment-related AE as assessed by NCI CTCAE version 4.03 |
| •biomarker | 24months | NGS, nanostring technology |
Countries
South Korea
Outcome results
None listed