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Trial record 93 of 1321 for:    Recruiting, Not yet recruiting, Available Studies | "Head and Neck Neoplasms"

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

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ClinicalTrials.gov Identifier: NCT03292250
Recruitment Status : Recruiting
First Posted : September 25, 2017
Last Update Posted : October 11, 2017
Sponsor:
Collaborators:
Korean Cancer Study Group
Chungnam National University Hospital
Information provided by (Responsible Party):
Seoul National University Hospital

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

Condition or disease Intervention/treatment Phase
HNSCC Head and Neck Neoplasms Drug: BYL719 Drug: Poziotinib Drug: Nintedanib Drug: Abemaciclib Drug: Durvalumab,Tremelimumab Phase 2

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 259 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
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.

Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Public-interest Multicenter Umbrella Trial Based on Genetic Analysis in Korean Head and Neck Cancer and Esophageal Cancer Patient - Part 1 (HNSCC)]
Actual Study Start Date : September 10, 2017
Estimated Primary Completion Date : January 1, 2020
Estimated Study Completion Date : December 31, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm1: BYL719
Experimental: BYL719 BYL719 is an oral class I α-specific PI3K inhibitor belonging to the 2-aminothiazole class of compounds.
Drug: BYL719
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.

Experimental: Arm2: Poziotinib
Experimental:Poziotinib Poziotinib is a pan-HER tyrosine kinase inhibitor.(oral class)
Drug: Poziotinib
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.

Experimental: Arm3: Nintedanib
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
Initial dose 200 mg twice per day orally according to study protocol.

Experimental: Arm4: Abemaciclib
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
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.

Experimental: Arm5: Durvalumab,Tremelimumab

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




Primary Outcome Measures :
  1. Disease control rate (DCR) [ Time Frame: 24 months ]
    Arm 1: RECIST version 1.1

  2. Response rate (RR) [ Time Frame: 24 months ]
    Arm 2-5: RECIST version 1.1


Secondary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: 24 months ]
    RECIST version 1.1

  2. Progression-free survival (PFS) [ Time Frame: 24 months ]
    RECIST version 1.1

  3. Overall survival (OS) [ Time Frame: 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

  4. Time to progression (TTP) [ Time Frame: 24 months ]
    RECIST version 1.1

  5. Quality of life assessment [ Time Frame: 24 months ]
    FACT-H&N (Version 4.0)

  6. Duration of response [ Time Frame: 24 months ]
    RECIST version 1.1

  7. Toxicity: Number of patients with treatment-related AE as assessed by NCI CTCAE version 4.03 [ Time Frame: 24 months ]
    number of patients with treatment-related AE as assessed by NCI CTCAE version 4.03

  8. biomarker [ Time Frame: 24 months ]
    NGS, nanostring



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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 / exclusion criteria, the specific drug Inclusion / exclusion criteria for the drug study should be met.

Arm 1: BYL719

BYL719 Specific Inclusion Criteria

  • 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

BYL719 Specific Exclusion Criteria

  • 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.

Arm 2: poziotinib

poziotinib Specific Inclusion Criteria

  • Patients with relevant genetic alterations including EGFR/HER2 pathway alteration or those by physician's discretion based on next generation sequencing (NGS).

poziotinib Specific Exclusion Criteria

  • Previous treatment with small molecule EGFR tyrosine kinase inhibitors (Cetuximab is permitted)
  • Patients with uncontrolled CNS metastatic involvement. However, corticosteroids should be discontinued at least 2 weeks before clinical trials, except for radiologic and neurologically stable cases for more than 4 weeks.
  • Patients with known interstitial lung disease
  • Patients with uncontrolled or significant cardiovascular disease (AMI ,Unstable angina within 6 months, NYHA Class III, IV Congestive heart failure or left ventricular ejection fraction below local institutional lower limit of normal or below 50%, Congenital long QT syndrome, Any significant ventricular arrhythmia, Any uncontrolled second or third degree heart block, Uncontrolled hypertension)
  • Any clinically significant gastrointestinal abnormalities which may impair intake or absorption of the study drug

Arm 3: nintedanib

nintedanib Specific Inclusion Criteria

  • Patients with relevant genetic alterations including FGFR athway alteration or those by physician's discretion based on next generation sequencing (NGS).
  • Life expectancy of at least 12 weeks

nintedanib Specific Exclusion Criteria

  • Prior treatment with FGFR pathway inhibitors
  • Recent bleeding history, major vessel invasion of tumour
  • Patient who cannot take the oral drug
  • Patients with active brain metastases (defined as stable for <4 weeks, no adequate previous treatment with radiotherapy, symptomatic, or requiring treatment with anticonvulsants). Patients with treated/controlled and asymptomatic CNS metastases may participate in this trial.
  • 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 who are currently receiving medication with a known risk of prolonging the QT interval or inducing Torsades de Pointes (TdP) and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug treatment
  • Therapeutic anticoagulation (except low-dose heparin or heparin flush in the catheter) or antiplatelet therapy (except for acetylsalicylic acid <325 mg / day)

Arm 4: abemaciclib

abemaciclib Specific Inclusion Criteria

  • p16 negative and genetic alterations in CDK4/6 pathway
  • Patients who received chemotherapy must have recovered (Common Terminology Criteria for Adverse Events [CTCAE] Grade ≤1) from the acute effects of chemotherapy except for residual alopecia or Grade 2 peripheral neuropathy prior to screening. A washout period of at least 21 days is required between last chemotherapy dose and screening (provided the patient did not receive radiotherapy).
  • Patients who received adjuvant radiotherapy must have completed and fully recovered from the acute effects of radiotherapy. A washout period of at least 14 days is required between end of radiotherapy and randomization

abemaciclib Specific Exclusion Criteria

  • Prior treatment with CDK4/6 pathway inhibitors
  • Recent significant bleeding history and major vessel invasion of tumor
  • Pregnant woman, Breast-feeding woman

    • If a female of childbearing potential, must have a negative serum pregnancy test within 7 days of the first dose of abemaciclib and agree to use a medically approved contraceptive method during the treatment period and for 3 months following the last dose of abemaciclib.
  • If a male, must agree to use a reliable method of birth control and to not donate sperm during the study and for at least 3 months following the last dose of abemaciclib. Contraceptive methods may include an intrauterine device [IUD] or barrier method. If condoms are used as a barrier method, a spermicidal agent should be added as a double barrier protection.
  • The patient has serious preexisting medical condition(s) that would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea).
  • Patient who cannot take the oral drug
  • 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)

Arm 5: durvalumab +/- tremelimumab

durvalumab +/- tremelimumab Specific Inclusion Criteria

  • NGS analysis on the molecular tumor board showed that there was no mutation corresponding to Arm 1 ~ 4 or Patients who were treated with Arm 1 ~ 4 and progressed to disease and who satisfied Arm5 criteria (Arm 1 ~ 4 allow cross over to Arm 5, but not the reverse.)

durvalumab +/- tremelimumab Specific Exclusion Criteria

  • Previous treatment with CTLA-4 , PD-1 or PDL-1 inhibitors
  • Symptomatic brain metastasis
  • Patients with known interstitial lung disease
  • Systemic immunosuppressive therapy
  • Active autoimmune disease 7 - Body weight <30kg
  • Other severe acute or chronic medical condition or laboratory abnormality that may increase the risk associated with trial participation
  • 12-Lead electrocardiogram (ECG) with abnormal tracing or clinically significant changes that require medical intervention
  • History of treatment with live vaccine within 30 days of drug administration for clinical trial

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03292250


Contacts
Contact: Bhumsuk Keam 82-2-2072-7215 bhumsuk@snu.ac.kr

Locations
Korea, Republic of
Seoul National University Hospital Recruiting
Seoul, Korea, Republic of, 110-744
Contact: Bhumsuk Keam, MD    82-2-2072-7215    bhumsuk@snu.ac.kr   
Principal Investigator: Hye Ryun Kim         
Principal Investigator: Hwan Jung Yun         
Principal Investigator: Myung-Ju Ahn         
Principal Investigator: Sung Bae Kim         
Principal Investigator: Hyun Chang         
Principal Investigator: Sang Hoon Chun         
Principal Investigator: InSook Woo         
Principal Investigator: Yoon Ho Ko         
Principal Investigator: Ji Hyung Hong         
Principal Investigator: jung hye kwon         
Principal Investigator: Heui-june Ahn         
Principal Investigator: Yun Gyoo Lee         
Principal Investigator: Keonuk Park         
Principal Investigator: Eun Joo Kang         
Principal Investigator: Seong-Hoon Shin         
Principal Investigator: Tak Yun         
Principal Investigator: Yoon Hee Choi         
Principal Investigator: Keun-Wook Lee         
Principal Investigator: Joo-Hang Kim         
Principal Investigator: JinSoo Kim         
Principal Investigator: Sang-Cheol Lee         
Principal Investigator: Hyun Woo Lee         
Principal Investigator: Min Kyoung Kim         
Principal Investigator: Hyeok Shim         
Principal Investigator: Seung taek Lim         
Principal Investigator: Kyoung Eun Lee         
Principal Investigator: Moon Young Choi         
Principal Investigator: Joohan Lim         
Principal Investigator: In Gyu Hwang         
Principal Investigator: Hyo Jung Kim         
Principal Investigator: Jun Eul Hwang         
Principal Investigator: Ho Jung An         
Principal Investigator: So Yeon Oh         
Principal Investigator: Sang-Gon Park         
Principal Investigator: Hee Kyoung Ahn         
Principal Investigator: Sun Min Lim         
Sponsors and Collaborators
Seoul National University Hospital
Korean Cancer Study Group
Chungnam National University Hospital
Investigators
Study Chair: Hwan Jung Yun Chungnam National University Hospital

Responsible Party: Seoul National University Hospital
ClinicalTrials.gov Identifier: NCT03292250     History of Changes
Other Study ID Numbers: KCSG-TRIUMPH
First Posted: September 25, 2017    Key Record Dates
Last Update Posted: October 11, 2017
Last Verified: September 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: anticipated as research paper

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Seoul National University Hospital:
NGS
Nanostring
Biomarker Driven Umbrella Trial
BYL719,poziotinib, abemaciclib, nintedanib
Durvalumab + Tremelimumab Combination Treatment

Additional relevant MeSH terms:
Head and Neck Neoplasms
Neoplasms by Site
Neoplasms
Antibodies, Monoclonal
Tremelimumab
Nintedanib
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action