Head and Neck Neoplasms, HNSCC
Conditions
Keywords
NGS, Nanostring, Biomarker Driven Umbrella Trial, BYL719,poziotinib, abemaciclib, nintedanib, Durvalumab + Tremelimumab Combination Treatment
Brief summary
Open, multicenter, single arm, phase II, biomarker driven umbrella trial for head and neck squamous cell carcinoma
Detailed description
This study will be conducted as a part of umbrella trial by Korean Cancer Study Group. The brief scheme of this umbrella trial is as follows: R/M HNSCC 2nd line 1. PI3K inhibitor - BYL719 (from Norvatis) 2. EGFR/HER2 inhibitor - poziotinib (from Hanmi pharmaceutical) 3. FGFR inhibitor - nintedanib (from Boehringer ingelheim) 4. Cell cycle (CDK4/6) inhibitor - abemaciclib (from Lily) 5. Others- anti PD1/PD-L1 - durvalumab+/-tremelimumab (from AZ) During or after palliative 1st line platinum based chemotherapy, we will perform prescreening NGS based molecular characterization. The molecular characterization will be done by following three methods. * NGS : Agilent SureSelect Target Enrichment (245 genes) * Nanostring nCounter including immune signature * IHC : PD-L1, CD8 TIL, p16 Mutation will be analyzed by NGS, fusion and amplification will be determined by Nanostring methods, and PD-L1/p16 status will be determined by immunohistopathology. Molecular tumor board to determine characterization will be held for every patients. Once each patients have relevant genetic pathway, the patients will be allocated each treatment arm (see below figure). If the patients have no relevant genetic alteration, such a patients will allocated to durvalumab+/- tremelimumab arm regardeless of PD-L1 positivity. If the patients who allocated to poziotinib, BYL719, nintedanib, and abemaciclib experience disease progression but still meet the inclusion/ exclusion criteria for durvalumab+/- tremelimumab arm, the cross over to durvalumab+/- tremelimumab arm will be permitted. Vice versa (cross over from durvalumab+/- tremelimumab arm to another arms) is not permitted.
Interventions
DRUGNintedanib
Initial dose 200 mg twice per day orally according to study protocol.
DRUGBYL719
Patients will be instructed to take BYL719 orally at a dose of 100 mg with a glass of water once daily, in a fasting state or with a light fat-free meal, and as close as possible to the same time each day.
DRUGPoziotinib
Patients will be instructed to take BYL719 orally at a dose of 12 mg once daily, in a fasting state or with a light fat-free meal, and as close as possible to the same time each day.
DRUGAbemaciclib
Patients will be instructed to take Abemaciclib orally at a dose of 200mg bid with a glass of water twice daily, in a fasting state or with a light fat-free meal, and as close as possible to the same time each day.
Durvalumab: 1.5g Q4W plusTremelimumab: 75mg Q4W up to 4cycle then Durvalumab 750mg Q2W, till PD or unacceptable toxicity.
Sponsors
Korean Cancer Study Group
Chungnam National University Hospital
Seoul National University Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
During or after palliative 1st line platinum based chemotherapy, we will perform prescreening NGS based molecular characterization. Molecular tumor board to determine characterization will be held for every patients. Once each patients have relevant genetic pathway, the patients will be allocated each treatment arm.If the patients have no relevant genetic alteration, such a patients will allocated to durvalumab+/- tremelimumab arm regardeless of PD-L1 positivity. If the patients who allocated to BYL719(Arm1),poziotinib(Arm2), nintedanib(Arm3), and abemaciclib(Arm4) experience disease progression but still meet the inclusion/ exclusion criteria for durvalumab+/- tremelimumab arm((Arm5) the cross over to durvalumab+/- tremelimumab arm will be permitted. Vice versa (cross over from durvalumab+/- tremelimumab arm to another arms) is not permitted.
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Common Inclusion Criteria: The following criteria must all be met. * Histologically or cytologically confirmed recurrent or metastatic SCCHN * Ineligibility for local therapy (surgery or radiation for curative intent) * 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 palliative chemotherapyAt least one measurable lesion by RECIST ver 1.1 * Age ≥20 * ECOG performance status of 0-1 * Adequate organ function for treatment * Absolute neutrophil count (ANC) ≥1500 cells/mm3 * Platelets ≥100,000 cells/mm3 * Hemoglobin ≥ 9 g/dL. * Serum creatinine \<1.5 x institution upper limit of normal * Bilirubin ≤1.5 x upper limit of normal (ULN) * AST (SGOT) ≤3.0 x ULN * ALT (SGPT) ≤3.0 x ULN * At least one lesion that is measurable according to the RECIST 1.1 criteria by CT or MRI * The patient has provided signed informed consent and has a compliance to follow the study protocol. Common Inclusion Criteria: Patients eligible for this study should not meet any of the following criteria: * Nasopharyngeal carcinoma * Major surgery within 4 weeks prior to initiating study treatment * Patients who have received prior systemic chemotherapy, immunotherapy or study drug within 4 weeks (Exclusion of conventional radiotherapy for non-target lesions within 2 weeks prior to enrollment) * Pregnant woman, Breast-feeding woman * Females who were not screened for pregnancy or had positive results. (Women are considered post-menopausal and not of child bearing potential if they have had 12 months of amenorrhea or have had surgical bilateral oophorectomy or Age ≥60 * Previous or concomitant malignant disease, except adequately treated basal cell cancer of the skin or cervical cancer in situ, superficial bladder tumors (Ta, Tis & T1) or any cancer curatively treated \> 3 years prior study entry * Other severe acute or chronic medical condition or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results and, in the judgment of the investigator, would make the patient inappropriate for entry into this trial (infection/inflammation, intestinal obstruction, social/psychological complications) * Patients with significant cardiovascular disease or within AMI 12 months, (Congestive heart failure or Any significant ventricular arrhythmia) * Patients who received organ transplants requiring immunosuppressive therapy * Patients with HBsAg, anti-HCV, HIV-positive patients or other uncontrolled infectious diseases * However, Arm1-Arm3 Inactivated hepatitis B carriers using appropriate prophylactic antiviral agents can be listed at the discretion of the investigator * Arm5: An active HBV carrier who has received HBV DNA \<100 IU / mL at the time of screening, has received appropriate prophylactic antiviral treatment and continues to receive treatment with an antiviral agent during the trial can be registered. Specific Inclusion
Exclusion criteria
In addition to the common Inclusion /
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease control rate (DCR) | 24 months | Arm 1: RECIST version 1.1 |
| Response rate (RR) | 24 months | Arm 2-5: RECIST version 1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival (OS) | 24 months | 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 |
| Time to progression (TTP) | 24 months | RECIST version 1.1 |
| Quality of life assessment | 24 months | FACT-H&N (Version 4.0) |
| Overall Response Rate (ORR) | 24 months | RECIST version 1.1 |
| Toxicity: Number of patients with treatment-related AE as assessed by NCI CTCAE version 4.03 | 24 months | number of patients with treatment-related AE as assessed by NCI CTCAE version 4.03 |
| biomarker | 24 months | NGS, nanostring |
| Duration of response | 24 months | RECIST version 1.1 |
| Progression-free survival (PFS) | 24 months | RECIST version 1.1 |
Countries
South Korea
Outcome results
None listed