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A Biomarker-driven, Open Label, Single Arm, Multicentre Phase II Study of Abemaciclib in Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma Who Failed to Platinum-based Therapy

Primary Purpose

HNSCC, Head and Neck Neoplasms

Status
Unknown status
Phase
Phase 2
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Abemaciclib
Sponsored by
Seoul National University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for HNSCC focused on measuring NGS, Nanostring, Biomarker Driven Umbrella Trial, abemaciclib

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • (1) Histologically or cytologically confirmed recurrent or metastatic HNSCC, except nasopharyngeal carcinoma (2) Age ≥20 (3) ECOG performance status of 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 palliative chemotherapy (6) At least one measurable lesion by RECIST ver 1.1 (7) p16 negative and intact Rb and genetic alterations in CDK4/6 pathway (8) Adequate organ function for all of the following criteria, as defined below.
  • Absolute neutrophil count (ANC) ≥1500 cells/mm3
  • Platelets ≥100,000 cells/mm3
  • Hemoglobin ≥ 8 g/dL (Patients may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator. Initial treatment must not begin earlier than the day after the erythrocyte transfusion.)
  • Serum creatinine ≤1.5 x institution upper limit of normal
  • Total Bilirubin ≤1.5 x upper limit of normal (ULN) (Patients with Gilbert's syndrome with a total bilirubin ≤2.0 times ULN and direct bilirubin within normal limits are permitted.)
  • AST (SGOT) ≤3.0 x ULN
  • ALT (SGPT) ≤3.0 x ULN (9) 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.

(10) 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).

(11) 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.

(12) The patient has provided signed informed consent and has a compliance to follow the study protocol.

(13) The patient is able to swallow oral medications.

Exclusion Criteria:

  • (1) Prior treatment with CDK4/6 pathway inhibitors (2) Nasopharyngeal carcinoma (3) 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).

    (4) Pregnant woman, Breast-feeding woman (5) Recent significant bleeding history within 6 major vessel invasion of tumor (6) 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).

    (7) 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) (8) The patient has a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest.

Sites / Locations

  • Seoul National University HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm4: Abemaciclib

Arm Description

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

Outcomes

Primary Outcome Measures

Response rate (RR)
RECIST version 1.1

Secondary Outcome Measures

Progression-free survival (PFS)
RECIST version 1.1
Overall survival (OS)
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
Duration of response
RECIST version 1.1
Toxicity
number of patients with treatment-related AE as assessed by NCI CTCAE version 4.03

Full Information

First Posted
November 24, 2017
Last Updated
November 24, 2017
Sponsor
Seoul National University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT03356587
Brief Title
A Biomarker-driven, Open Label, Single Arm, Multicentre Phase II Study of Abemaciclib in Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma Who Failed to Platinum-based Therapy
Official Title
A Biomarker-driven, Open Label, Single Arm, Multicentre Phase II Study of Abemaciclib in Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma Who Failed to Platinum-based Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
September 2017
Overall Recruitment Status
Unknown status
Study Start Date
October 16, 2017 (Actual)
Primary Completion Date
January 1, 2020 (Anticipated)
Study Completion Date
December 31, 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Seoul National University Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Open, multicenter, single arm, phase II, biomarker driven umbrella trial for head and neck squamous cell carcinoma (FGFR inhibitor, CDK4/6 inhibitor, pan HER inhibitor, PI3K inhibitor, PD1/PD-L1 inhibitor)
Detailed Description
This study will be conducted as a treatment arm 4 of the umbrella clinical trial.(NCT03292250) 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 The present trial will investigate the efficacy and safety of abemaciclib in patients with recurrent or metastatic HPV (-) HNSCC with genetic alterations of cell cycle pathway who failed to platinum-based therapy. We will also evaluate feasibility and the effect on decision making of next generation sequencing of HNSCC.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HNSCC, Head and Neck Neoplasms
Keywords
NGS, Nanostring, Biomarker Driven Umbrella Trial, abemaciclib

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
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
Masking
None (Open Label)
Allocation
N/A
Enrollment
32 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm4: Abemaciclib
Arm Type
Experimental
Arm Description
Abemaciclib represents a selective and potent small molecule CDK4 and CDK6 dual inhibitor with broad antitumor activity in preclinical pharmacology models.(oral class) 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
Intervention Type
Drug
Intervention Name(s)
Abemaciclib
Intervention Description
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
Primary Outcome Measure Information:
Title
Response rate (RR)
Description
RECIST version 1.1
Time Frame
24 months
Secondary Outcome Measure Information:
Title
Progression-free survival (PFS)
Description
RECIST version 1.1
Time Frame
24 months
Title
Overall survival (OS)
Description
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 Frame
24 months
Title
Duration of response
Description
RECIST version 1.1
Time Frame
24 months
Title
Toxicity
Description
number of patients with treatment-related AE as assessed by NCI CTCAE version 4.03
Time Frame
24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: (1) Histologically or cytologically confirmed recurrent or metastatic HNSCC, except nasopharyngeal carcinoma (2) Age ≥20 (3) ECOG performance status of 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 palliative chemotherapy (6) At least one measurable lesion by RECIST ver 1.1 (7) p16 negative and intact Rb and genetic alterations in CDK4/6 pathway (8) Adequate organ function for all of the following criteria, as defined below. Absolute neutrophil count (ANC) ≥1500 cells/mm3 Platelets ≥100,000 cells/mm3 Hemoglobin ≥ 8 g/dL (Patients may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator. Initial treatment must not begin earlier than the day after the erythrocyte transfusion.) Serum creatinine ≤1.5 x institution upper limit of normal Total Bilirubin ≤1.5 x upper limit of normal (ULN) (Patients with Gilbert's syndrome with a total bilirubin ≤2.0 times ULN and direct bilirubin within normal limits are permitted.) AST (SGOT) ≤3.0 x ULN ALT (SGPT) ≤3.0 x ULN (9) 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. (10) 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). (11) 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. (12) The patient has provided signed informed consent and has a compliance to follow the study protocol. (13) The patient is able to swallow oral medications. Exclusion Criteria: (1) Prior treatment with CDK4/6 pathway inhibitors (2) Nasopharyngeal carcinoma (3) 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). (4) Pregnant woman, Breast-feeding woman (5) Recent significant bleeding history within 6 major vessel invasion of tumor (6) 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). (7) 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) (8) The patient has a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Bhumsuk Keam Keam
Phone
82-2-2072-7215
Email
bhumsuk@snu.ac.kr
Facility Information:
Facility Name
Seoul National University Hospital
City
Seoul
ZIP/Postal Code
110-744
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bhumsuk Keam, MD
Phone
82-2-2072-7215
Email
bhumsuk@snu.ac.kr
First Name & Middle Initial & Last Name & Degree
Hye Ryun Kim
First Name & Middle Initial & Last Name & Degree
Hwan Jung Yun
First Name & Middle Initial & Last Name & Degree
Myung-Ju Ahn
First Name & Middle Initial & Last Name & Degree
Sung Bae Kim
First Name & Middle Initial & Last Name & Degree
Hyun Chang
First Name & Middle Initial & Last Name & Degree
Sang Hoon Chun
First Name & Middle Initial & Last Name & Degree
InSook Woo
First Name & Middle Initial & Last Name & Degree
Yoon Ho Ko
First Name & Middle Initial & Last Name & Degree
Ji Hyung Hong
First Name & Middle Initial & Last Name & Degree
jung hye kwon
First Name & Middle Initial & Last Name & Degree
Heui-june Ahn
First Name & Middle Initial & Last Name & Degree
Yun Gyoo Lee
First Name & Middle Initial & Last Name & Degree
Keonuk Park
First Name & Middle Initial & Last Name & Degree
Eun Joo Kang
First Name & Middle Initial & Last Name & Degree
Seong-Hoon Shin
First Name & Middle Initial & Last Name & Degree
Tak Yun
First Name & Middle Initial & Last Name & Degree
Yoon Hee Choi
First Name & Middle Initial & Last Name & Degree
Keun-Wook Lee
First Name & Middle Initial & Last Name & Degree
Joo-Hang Kim
First Name & Middle Initial & Last Name & Degree
JinSoo Kim
First Name & Middle Initial & Last Name & Degree
Sang-Cheol Lee
First Name & Middle Initial & Last Name & Degree
Hyun Woo Lee
First Name & Middle Initial & Last Name & Degree
Min Kyoung Kim
First Name & Middle Initial & Last Name & Degree
Hyeok Shim
First Name & Middle Initial & Last Name & Degree
Seung taek Lim
First Name & Middle Initial & Last Name & Degree
Kyoung Eun Lee
First Name & Middle Initial & Last Name & Degree
Moon Young Choi
First Name & Middle Initial & Last Name & Degree
Joohan Lim
First Name & Middle Initial & Last Name & Degree
In Gyu Hwang
First Name & Middle Initial & Last Name & Degree
Hyo Jung Kim
First Name & Middle Initial & Last Name & Degree
Jun Eul Hwang
First Name & Middle Initial & Last Name & Degree
Ho Jung An
First Name & Middle Initial & Last Name & Degree
So Yeon Oh
First Name & Middle Initial & Last Name & Degree
Sang-Gon Park
First Name & Middle Initial & Last Name & Degree
Hee Kyoung Ahn
First Name & Middle Initial & Last Name & Degree
Sun Min Lim

12. IPD Sharing Statement

Plan to Share IPD
Undecided
IPD Sharing Plan Description
anticipated as research paper

Learn more about this trial

A Biomarker-driven, Open Label, Single Arm, Multicentre Phase II Study of Abemaciclib in Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma Who Failed to Platinum-based Therapy

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