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Phase I Study of BYL719 in Combination With Cisplatin and Radiotherapy in Patients With Squamous Cell Head and Neck Cancer

Primary Purpose

Squamous Cell Carcinoma of Head and Neck, Locoregionally Advanced

Status

Completed

Phase

Phase 1

Locations

Canada

Study Type

Interventional

Intervention

BYL719

Cisplatin

Intensity modulated radiation therapy (IMRT)

About this trial

This is an interventional treatment trial for Squamous Cell Carcinoma of Head and Neck

Eligibility Criteria

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

Inclusion Criteria:

Willing and able to comply with study requirements
Age >= 18 years
Life expectancy >6 months
Previously untreated locally advanced squamous cell carcinoma of the head and neck eligible for cisplatin-based chemoradiation
Not have received prior anti-neoplastic treatment within 2 years
Resolved toxicities to Grade 1 or less
Performance status of 0-1
Adequate organ function
Able to swallow and retain oral medication

Exclusion Criteria:

Enrolled on another intervention clinical trial or in prior study within 30 days.
Taking drugs with risk of prolonging the QT interval or of causing Torsades de Pointes
Any condition that could increase the risk to the patient by participating which may include:
Lung disease or uncontrolled hypertension
Cardiovascular/vascular/cardiac disease
Uncontrolled severe infection
Impaired lung function
Chronic treatment with corticosteroids/immunosuppressive agents
Not recovered from previous toxicities
Systemic therapy within 4 weeks of the start of the study treatment
Active bacterial, fungal or viral infection
Significant bleeding disorders
Uncontrolled medical disorder or active infection
Dementia or significantly altered mental status
Diabetes mellitus requiring insulin treatment
Another malignancy within 2 years of the start of the study treatment
Received live attenuated vaccines within 1 week of the start of the study treatment
Receiving treatment with drugs known to be moderate or strong inhibitors or inducers of isoenzymes CYP34A or CYP2C8
Have impaired gastrointestinal (GI) function or GI disease

Sites / Locations

Princess Margaret Cancer Centre

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

BYL719, Cisplatin, and Radiation Therapy

Arm Description

BYL719, orally, at a starting dose of 200-350 mg, once daily, for 7 weeks. Cisplatin, intravenously, at 100 mg/m2 over 1 hour, every 3 weeks for 3 doses. Radiation therapy, Monday to Friday, for 7 weeks.

Outcomes

Primary Outcome Measures

Number of Treatment Emergent Side Effects

Secondary Outcome Measures

Time from date of enrollment to date of relapse disease

Number of patients who do not have locoregional relapse of disease

Number of patients who do not have a distant metastatic relapse of disease

Time from date of enrolment to date of death

Full Information

NCT ID

NCT02537223

First Posted

August 28, 2015

Last Updated

April 16, 2021

Sponsor

University Health Network, Toronto

Collaborators

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT02537223

Brief Title

Phase I Study of BYL719 in Combination With Cisplatin and Radiotherapy in Patients With Squamous Cell Head and Neck Cancer

Official Title

Phase I Trial of BYL719 in Combination With Concurrent Cisplatin-based Chemoradiotherapy in Patients With Locoregionally Advanced Squamous Cell Carcinoma of Head and Neck (LA-SCCHN)

Study Type

Interventional

2. Study Status

Record Verification Date

April 2021

Overall Recruitment Status

Completed

Study Start Date

September 2015 (undefined)

Primary Completion Date

June 14, 2018 (Actual)

Study Completion Date

February 20, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University Health Network, Toronto

Collaborators

Novartis Pharmaceuticals

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

This is a phase 1 study (the first step in testing a new drug or combination, to see how safe the drug and/or combination are) of investigational agent BYL719 in patients with locally advanced head and neck cancer (LA-SCCHN) in combination with standard radiation and chemotherapy (cisplatin). BYL719 is a new drug that is able to bind (attach to) and block a protein called PI3K-alpha. PI3K-alpha is part of an important pathway called EGFR/PI3K/Akt. A pathway is a series of chemical reactions among proteins in the cells that are involved in the support of normal cellular function. If the pathway is too active, due to changes in those proteins, the pathway can lead to tumor cell growth, survival and invasion. BYL719 has been shown to stop cancers in laboratory and animal studies. This study is the first time BYL719 will be combined with radiation and chemotherapy.

Detailed Description

Participants will be screened for eligibility within 30 days of the intended start of the study treatment. Procedures for research purposes done during screening include archival tumor tissue collection for pharmacodynamic and predictive biomarker research and optional HPV status (if not already known). Eligible participants will take BYL719, by mouth, once a day, starting one week prior to start of radiation and chemotherapy, for 8 weeks. The starting dose of BYL719 is 200 mg. Participants will be asked to record their doses on a study drug diary. Participants will also receive radiation therapy every day from Monday to Friday for 7 weeks. Chemotherapy (cisplatin) will be given intravenously on Monday of weeks 1, 4, and 7 (48 hour window during weeks 4 and 7). While receiving the study treatment, participants will have tests and procedures done once every week for safety purposes. After the end of the study treatment, participants will be asked to visit the centre every 2 weeks up to week 8 for additional tests and procedures for safety purposes. Between week 8-12 after completing the study treatment, participants will have tumor measurements done to assess efficacy. Participants will continued to be followed every 3 months up to 1 year, then every 6 months for 2 years (total of 3 years).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Squamous Cell Carcinoma of Head and Neck, Locoregionally Advanced

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

9 (Actual)

8. Arms, Groups, and Interventions

Arm Title

BYL719, Cisplatin, and Radiation Therapy

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

BYL719

Intervention Type

Drug

Intervention Name(s)

Cisplatin

Intervention Type

Radiation

Intervention Name(s)

Intensity modulated radiation therapy (IMRT)

Primary Outcome Measure Information:

Title

Number of Treatment Emergent Side Effects

Time Frame

3 years

Secondary Outcome Measure Information:

Title

Time from date of enrollment to date of relapse disease

Time Frame

3 years

Title

Number of patients who do not have locoregional relapse of disease

Time Frame

6 months

Title

Number of patients who do not have locoregional relapse of disease

Time Frame

12 months

Title

Number of patients who do not have a distant metastatic relapse of disease

Time Frame

6 months

Title

Number of patients who do not have a distant metastatic relapse of disease

Time Frame

12 months

Title

Time from date of enrolment to date of death

Time Frame

3 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Willing and able to comply with study requirements Age >= 18 years Life expectancy >6 months Previously untreated locally advanced squamous cell carcinoma of the head and neck eligible for cisplatin-based chemoradiation Not have received prior anti-neoplastic treatment within 2 years Resolved toxicities to Grade 1 or less Performance status of 0-1 Adequate organ function Able to swallow and retain oral medication Exclusion Criteria: Enrolled on another intervention clinical trial or in prior study within 30 days. Taking drugs with risk of prolonging the QT interval or of causing Torsades de Pointes Any condition that could increase the risk to the patient by participating which may include: Lung disease or uncontrolled hypertension Cardiovascular/vascular/cardiac disease Uncontrolled severe infection Impaired lung function Chronic treatment with corticosteroids/immunosuppressive agents Not recovered from previous toxicities Systemic therapy within 4 weeks of the start of the study treatment Active bacterial, fungal or viral infection Significant bleeding disorders Uncontrolled medical disorder or active infection Dementia or significantly altered mental status Diabetes mellitus requiring insulin treatment Another malignancy within 2 years of the start of the study treatment Received live attenuated vaccines within 1 week of the start of the study treatment Receiving treatment with drugs known to be moderate or strong inhibitors or inducers of isoenzymes CYP34A or CYP2C8 Have impaired gastrointestinal (GI) function or GI disease

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Aaron Hansen, M.D.

Organizational Affiliation

Princess Margaret Cancer Centre

Official's Role

Principal Investigator

Facility Information:

Facility Name

Princess Margaret Cancer Centre

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M3G 2M9

Country

Canada

12. IPD Sharing Statement

Learn more about this trial

Phase I Study of BYL719 in Combination With Cisplatin and Radiotherapy in Patients With Squamous Cell Head and Neck Cancer

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