Korean Cancer Study Group: Translational bIomarker Driven UMbrella Project for Head and Neck (TRIUMPH), Esophageal Squamous Cell Carcinoma- Part 1 (HNSCC)]

NCT03292250 | Completed Phase 2

• 1 other identifier: KCSG-TRIUMPH
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

Brief Summary

Open, multicenter, single arm, phase II, biomarker driven umbrella trial for head and neck squamous cell carcinoma

Conditions

HNSCC; Head and Neck Neoplasms

Keywords

NGS; Nanostring; Biomarker Driven Umbrella Trial; BYL719,poziotinib, abemaciclib, nintedanib; Durvalumab + Tremelimumab Combination Treatment

Outcome Measures

Primary Outcomes (2)

• Disease control rate (DCR)

  Arm 1: RECIST version 1.1

  24 months

• Response rate (RR)

  Arm 2-5: RECIST version 1.1

  24 months

Secondary Outcomes (8)

• Overall Response Rate (ORR)

  24 months

• Progression-free survival (PFS)

  24 months

• Overall survival (OS)

  24 months

• Time to progression (TTP)

  24 months

• Quality of life assessment

  24 months

Study Arms (5)

Arm1: BYL719

EXPERIMENTAL

Experimental: BYL719 BYL719 is an oral class I α-specific PI3K inhibitor belonging to the 2-aminothiazole class of compounds.

Drug: BYL719

Arm2: Poziotinib

EXPERIMENTAL

Experimental:Poziotinib Poziotinib is a pan-HER tyrosine kinase inhibitor.(oral class)

Drug: Poziotinib

Arm3: Nintedanib

EXPERIMENTAL

Nintedanib is a potent small molecule triple receptor tyrosine kinase inhibitor (PDGFR, FGFR 1-3,VEGFR 1-3 ,VEGFR- 2) is considered to be the crucial receptor involved in initiation of the formation as well as the maintenance of tumour vasculature.(oral class)

Drug: Nintedanib

Arm4: Abemaciclib

EXPERIMENTAL

Abemaciclib represents a selective and potent small molecule CDK4 and CDK6 dual inhibitor with broad antitumor activity in preclinical pharmacology models.(oral class)

Drug: Abemaciclib

Arm5: Durvalumab,Tremelimumab

EXPERIMENTAL

Durvalumab is a human immunoglobulin (Ig) G1 kappa (IgG1κ) monoclonal antibody (mAb) that blocks the interaction of PD-L1 with PD-1 on T-cells and CD80 on immune cells and is engineered to reduce antibody-dependent cell-mediated cytotoxicity.(IV class) Tremelimumab is specific for human CTLA-4; cluster of differentiation a cell surface receptor that is expressed primarily on activated T cells and acts to inhibit their activation.(IV class)

Drug: Durvalumab,Tremelimumab

Interventions

BYL719 DRUG

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.

Arm1: BYL719

Poziotinib DRUG

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.

Arm2: Poziotinib

Nintedanib DRUG

Initial dose 200 mg twice per day orally according to study protocol.

Arm3: Nintedanib

Abemaciclib DRUG

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.

Arm4: Abemaciclib

Durvalumab,Tremelimumab DRUG

Durvalumab: 1.5g Q4W plusTremelimumab: 75mg Q4W up to 4cycle then Durvalumab 750mg Q2W, till PD or unacceptable toxicity.

Arm5: Durvalumab,Tremelimumab

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Arm 1: BYL719
• Patients with relevant genetic alterations including PI3K pathway alteration or those by physician's discretion based on next generation sequencing (NGS).
• Uncontrolled, untreated brain metastasis. Patients with treated/controlled and asymptomatic CNS metastases may participate in this trial. The patient must have completed any prior treatment for CNS metastases ≥ 28 days (must include radiotherapy and/or surgery) and, if on corticosteroid therapy, should be receiving a stable low dose (e.g. dexamethasone 4 mg or equivalent dose of another corticosteroid for at least 14 days before start of study treatment).
• Life expectancy of at least 12 weeks
• Prior treatment with AKT. mTOR PI3K pathway inhibitors
• Patient who cannot take the oral drug
• Impaired GI function or GI disease that may significantly alter the absorption of oral BYL719 (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
• Other severe acute or chronic medical condition or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration
• Clinically significant cardiac disease or impaired cardiac function, such as:
• Congestive heart failure (CHF) requiring treatment (New Yort Heart Association (NYHA) Grade ≥ 2)
• left ventricular ejection fraction (LVEF) \< 50% as determined by multi-gated acquisition (MUGA) scan or echocardiogram
• uncontrolled arterial hypertension defined by blood pressure \> 140/100 mmHg at rest (average of 3 consecutive readings)
• History or current evidence of clinically significant cardiac arrhythmias, arterial fibrillation and/or conduction abnormality, e.g. congenical long QT syndrome, high grade/complete AV-blockage
• Acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass graft (CABG), coronary angioplasty, or stenting), \< 3 months prior to screening, QTcF\> 480 msec on screening ECG
• Patients with diabetes mellitus requiring insulin treatment and/or with clinical signs or with FPG ≥ 140 mg/dL/7.8mmol/L, or history of documented steroid-induced diabetes mellitus.

Sponsors & Collaborators

• Seoul National University Hospital: lead
• Korean Cancer Study Group: collaborator
• Chungnam National University Hospital: collaborator

Study Sites (1)

Seoul National University Hospital

Seoul, 110-744, South Korea

Location

Related Publications (1)

• Keam B, Hong MH, Shin SH, Heo SG, Kim JE, Ahn HK, Lee YG, Park KU, Yun T, Lee KW, Kim SB, Lee SC, Kim MK, Cho SH, Oh SY, Park SG, Hwang S, Nam BH, Kim S, Kim HR, Yun HJ; KCSG TRIUMPH Investigators. Personalized Biomarker-Based Umbrella Trial for Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: KCSG HN 15-16 TRIUMPH Trial. J Clin Oncol. 2024 Feb 10;42(5):507-517. doi: 10.1200/JCO.22.02786. Epub 2023 Sep 12.

  PMID: 37699162 DERIVED

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms

Interventions

Alpelisib; HM781-36B; nintedanib; abemaciclib; durvalumab; tremelimumab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site

Study Officials

• Hwan Jung Yun

  Chungnam National University Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: September 21, 2017
• First Posted: September 25, 2017
• Study Start: September 10, 2017
• Primary Completion: March 1, 2020
• Study Completion: March 10, 2022
• Last Updated: March 29, 2022

Record last verified: 2022-03

Locations

KR (1)