Dacomitinib Plus Radiotherapy, With and Without Cisplatin in Patients With Squamous Cell Carcinoma of the Head and Neck

June 9, 2016 updated by: University Health Network, Toronto

Phase I Trial of Dacomitinib Concomitant With Radiotherapy With and Without Cisplatin in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck

This is a phase 1 study of the drug dacomitinib with radiotherapy, with or without chemotherapy, in patients with advanced squamous cell carcinoma of the head and neck (SCCHN).

Dacomitinib is an oral drug, which is found to be active in SCCHN patients, blocks a receptor called the epidermal growth factor receptor (EGFR). By blocking signals for cancer cells to grow, it is believed to stop or slow the growth of tumor cells.

The dose escalation phase will find the best dose as well as determine the safety of dacomitinib when given with radiotherapy and with or without chemotherapy.The dose expansion phase will further test the best dose determined in the dose escalation phase for response rate.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a phase 1 study of the investigational drug, dacomitinib, with radiotherapy and with or without chemotherapy in patients with advanced squamous cell carcinoma of the head and neck (SCCHN).

There are proteins found on the surface of cells called receptors that receive signals and send signals to the cell to grow or to die. Dacomitinib is an oral drug that blocks a receptor called the epidermal growth factor receptor (EGFR) which is found to be too active in SCCHN patients. By blocking the signals for the cancer cells to grow, it is believed to stop or slow the growth of tumor cells. The treatment of SCCHN usually includes chemotherapy and radiation.

The primary objectives of this study will have two phases: a dose escalation phase and a dose expansion phase. The dose escalation phase will find the best dose as well as determine the safety of dacomitinib when given with radiotherapy and with or without chemotherapy.The dose expansion phase will further test the best dose determined in the dose escalation phase for safety and response rate.

The secondary objectives are to evaluate the pharmacokinetic properties of the combination therapies, and to provide preliminary survival data.

Study Type

Interventional

Enrollment (Actual)

12

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Princess Margaret Cancer Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Signed voluntary informed consent provided.
  • Patient willing and able to comply with visits, treatment plan, pharmacokinetics, laboratory tests, other study procedures.
  • Escalation: Arm A: patients with local/locally advanced confirmed SCCHN; candidates for radical radiotherapy. Arm B: previously untreated patients, with locally advanced, confirmed SCCHN; candidates for radical concurrent cisplatin-based chemoradiation.
  • Expansion: previously untreated patients, with locally advanced, confirmed SCCHN; HPV-negative candidates for radical concurrent cisplatin-based chemoradiation.Note: Those with primary tumors of head and neck in nasopharynx, skin, or unknown are excluded.
  • Prior treatment of current neoplasm not allowed; must not have received any anti-neoplastic treatment within 2 years.
  • Treatment-related toxicity must have recovered to CTCAE Grade 1 (v.4.0) or baseline, except toxicities not considered a risk. Chronic dysphagia, xerostomia or other effect resulting from prior surgery will not be considered exclusion criterion.
  • ECOG performance status 0-1.
  • Patient must have adequate organ function determined by: Creatinine clearance of ≥ 50 mL/min using formula: Creatinine clearance=[(140-age) x wt (kg) x Constant]/creatinine (µmol/L) [Constant = 1.23 for men; 1.04 for women]. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L; Leukocytes > 3.0 x 109/L; Hemoglobin > 80 g/L (or > 8 g/dL); Platelets ≥ 100 x 109/L. Total bilirubin ≤ ULN; AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN. 12-Lead electrocardiogram (ECG) with normal tracing, or clinically non-significant changes. QTc interval < 480 msec, without history of Torsades de Pointes or other QTc abnormality.

Exclusion Criteria:

  • Enrollment in another clinical trial.
  • Prior trial drug use within 30 days or 5 half-lives preceding first dose of study medication.
  • Prior treatment with agents targeted to epidermal growth factor receptor
  • Requirement for drugs highly dependent on CYP2D6 for metabolism - dacomitinib is a potent CYP2D6 inhibitor [See Appendix B and C].
  • Patients taking drugs causing risk for Torsades de Pointes
  • Any acute/chronic medical, psychiatric, laboratory abnormality that investigator finds could increase risks of participation, trial drug administration or could interfere with trial results. Including: History of interstitial lung disease; uncontrolled hypertension, unstable angina, myocardial infarction, symptomatic congestive heart failure within a year, cardiac arrhythmia, diagnosed/suspected congenital long QT syndrome; cardiovascular or vascular disease with anti arrhythmic therapy and/or major changes to medical care within 6 months; active bacterial, fungal or viral infection including hepatitis B or C, and human immunodeficiency virus. Testing not required for patients with no symptoms of infection. History of bleeding disorder, or concurrent medications the investigator finds to potentially lead to unacceptable coagulation function, including: congenital bleeding disorders; acquired bleeding disorder within one year; Other serious uncontrolled medical disorder or active infection that investigator determines may impair ability to receive study treatment. Dementia or altered mental status that limits ability to obtain informed consent and compliance with requirements of protocol.
  • Breastfeeding/pregnancy. Females with reproductive potential [any female who had menarche and who has not had successful surgical sterilization/is not postmenopausal (defined as amenorrhea >12 consecutive months/women on hormone replacement therapy with serum follicle stimulating hormone level >35 mL.U/mL)] require negative pregnancy test within 72 hours of treatment.
  • Patients of reproductive potential/partners must agree to effective contraception while receiving trial treatment and for 3 months after. Effective contraception will be judgment of principal investigator or designate.
  • Inability or lack of willingness to comply

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dacomitinib with Radiotherapy
Dacomitinib, 15mg to 45mg orally, once daily. Radiotherapy, once daily (Monday to Friday) over six weeks.One day on weeks 2 to 6 the participants will receive treatment twice daily (bid).
Drug: dacomitinib
Tablets are administered orally or through a G-Tube, and can be taken with or without food.
Other Names:
  • PF-00299804
Radiation: Radiotherapy
Intensity modulated radiation therapy (IMRT) delivered using 4 or 6 MV photons. Patients will receive either the standard dose fractionation radiotherapy or accelerated fractionation radiotherapy.
Experimental: Dacomitinib and Chemoradiotherapy
Dacomitinib: 15mg to 45mg orally, once daily. Radiotherapy: Once daily (Monday to Friday) over seven weeks. Twice daily (bid) treatments may be introduced to compensate for treatment days missed due to statutory holidays, or machine maintenance. Cisplatin: 100mg/m2 intravenously; weeks 1, 4, and 7.
Drug: dacomitinib
Tablets are administered orally or through a G-Tube, and can be taken with or without food.
Other Names:
  • PF-00299804
Radiation: Radiotherapy
Intensity modulated radiation therapy (IMRT) delivered using 4 or 6 MV photons. Patients will receive either the standard dose fractionation radiotherapy or accelerated fractionation radiotherapy.
Drug: Cisplatin
If selected for this arm, cisplatin will be administered intravenously every three weeks after receiving premedications.
Other Names:
  • cisplatinum

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Maximum Tolerated Dose (in mg) of Dacomitinib
Time Frame: 1 year
1 year
To preliminarily evaluate the response rate of the combination of Dacomitinib, Cisplatin and Radiation
Time Frame: 1 year
1 year

Secondary Outcome Measures

Outcome Measure
Time Frame
Levels of Dacomitinib in the Blood (Pharmacokinetics) in Combination with Cisplatin and Radiation
Time Frame: Days 8, 22 and 43 (+2 day window) after initial dose
Days 8, 22 and 43 (+2 day window) after initial dose
Disease free survival, overall survival and locoregional and distant metastasis free survival
Time Frame: 6 and 12 months
6 and 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Health Network, Toronto

Investigators

  • Principal Investigator: Lillian Siu, M.D., Princess Margaret Cancer Centre/University Health Network

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2013

Primary Completion (Actual)

February 1, 2015

Study Completion (Actual)

May 1, 2015

Study Registration Dates

First Submitted

November 26, 2012

First Submitted That Met QC Criteria

November 28, 2012

First Posted (Estimate)

November 29, 2012

Study Record Updates

Last Update Posted (Estimate)

June 13, 2016

Last Update Submitted That Met QC Criteria

June 9, 2016

Last Verified

June 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • XDC-001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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