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

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by University Health Network, Toronto
Sponsor:
Information provided by (Responsible Party):
University Health Network, Toronto
ClinicalTrials.gov Identifier:
NCT01737008
First received: November 26, 2012
Last updated: November 21, 2013
Last verified: November 2013
  Purpose

This is a phase 1 study of 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.

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 effectiveness.


Condition Intervention Phase
Squamous Cell Carcinoma of the Head and Neck
Drug: Dacomitinib
Radiation: Radiotherapy
Drug: Cisplatin
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by University Health Network, Toronto:

Primary Outcome Measures:
  • Maximum Tolerated Dose (in mg) of Dacomitinib [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Number of Participants with Adverse Events [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • Number of Participants and Length of Time That Participants are Disease Free [ Time Frame: 6 and 12 months ] [ Designated as safety issue: No ]
  • Number of Participants who are Alive after 6 and 12 Months Post Completion of Treatment [ Time Frame: 6 and 12 months ] [ Designated as safety issue: No ]
  • Number of Participants and Length of Time That Participants do not Experience Distant Metastasis [ Time Frame: 6 and 12 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 34
Study Start Date: January 2013
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Other Name: PF-00299804
Radiation: 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
Other Name: PF-00299804
Radiation: Radiotherapy Drug: Cisplatin

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed written and voluntary informed consent provided.
  • Patient must be willing and able to comply with scheduled visits, treatment plan, pharmacokinetic assessments, laboratory tests and other study procedures.
  • Age ≥ 18 years, male or female.
  • Dose escalation phase: Arm A: patients with local or locally advanced, histologically or cytologically confirmed SCCHN, candidates for radical radiotherapy might be eligible. Arm B: previously untreated patients, with locally advanced, histologically or cytologically confirmed SCCHN candidates for radical concurrent cisplatin-based chemoradiation will be eligible.
  • Dose expansion phase: previously untreated patients, with locally advanced, histologically or cytologically confirmed SCCHN, HPV-negative determined by lack of p16 immunohistochemical staining, candidates for radical concurrent cisplatin-based chemoradiation will be eligible. Note: Patients with primary tumors of head and neck in nasopharynx, skin, or unknown are excluded.
  • Prior treatment with biological agents targeted to the epidermal growth factor receptor is not allowed.
  • Prior chemotherapy or radiotherapy for the treatment of the current neoplasm is not allowed
  • Patient must not have received any prior anti-neoplastic treatment within the past 2 years.
  • Any treatment-related acute toxicity, including laboratory abnormalities, must have recovered to CTCAE Grade 1 (NCI CTCAE v.4.0) or baseline, except toxicity not considered a safety risk. Chronic dysphagia or xerostomia or other local effect resulting from prior surgery will not be considered an exclusion criterion.
  • ECOG performance status of 0-1.
  • Patient must have adequate organ function as determined by the following criteria for:

    • Renal function: Estimated creatinine clearance of ≥ 50 mL/min using the following formula: Creatinine clearance = [(140-age) x wt (kg) x Constant] / creatinine (µmol/L) [Constant = 1.23 for men and 1.04 for women]
    • Bone marrow function (without hematopoietic growth factors or transfusion): 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
    • Liver function: Total bilirubin ≤ ULN; AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN
    • Cardiac function: 12-Lead electrocardiogram (ECG) with normal tracing, or clinically non-significant changes that do not require medical intervention. QTc interval < 480 msec, and without history of Torsades de Pointes or other symptomatic QTc abnormality.

Exclusion Criteria:

  • Patient cannot be concurrently enrolled on another clinical trial while enrolled on this study.
  • Prior investigational drug therapy within 30 days or 5 half-lives preceding the first dose of study medication (whichever is longer).
  • Requirement for treatment with drugs that are highly dependent on CYP2D6 for metabolism since dacomitinib is a potent CYP2D6 inhibitor in in vitro assays. [See Appendix B: prohibited medication list; Appendix C: use with caution medication list].
  • Patients currently taking drugs that are generally accepted to have a risk of causing Torsades de Pointes
  • Any acute or chronic medical or psychiatric condition or laboratory abnormality that could increase the risk associated with trial participation or trial drug administration or could interfere with the interpretation of trial results and, in the judgment of the investigator, would make the patient inappropriate for entry in the trial. This includes:

    • History of interstitial lung disease;
    • Uncontrolled hypertension, unstable angina, myocardial infarction or symptomatic congestive heart failure within the past 12 months or serious uncontrolled cardiac arrhythmia, diagnosed or suspected congenital long QT syndrome;
    • Patients with minimally symptomatic cardiovascular (e.g. ischemic heart disease, congestive cardiac failure, arrhythmia) or vascular disease (e.g. stroke, deep venous thrombosis) who had anti arrhythmic therapy and/or significant changes to medical care within 6 months to enrolment;
    • Active bacterial, fungal or viral infection including hepatitis B (HBV), hepatitis C (HCV), and human immunodeficiency virus (HIV). Serological testing will not be required at baseline for patients who have no symptoms suggestive of infection.
    • History of significant bleeding disorder, or concurrent medications that are felt in the opinion of the investigator to potentially lead to unacceptable coagulation function during perioperative interval, including:
    • Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease);
    • Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies).
    • Other serious uncontrolled medical disorder or active infection that would impair the ability to receive study treatment as determined by the investigator.
    • Dementia or significantly altered mental status that would limit the ability to obtain informed consent and compliance with the requirements of this protocol.
  • Female patients who are breastfeeding or pregnant are excluded. All female patients with reproductive potential must have a negative pregnancy test (serum/urine) within 72 hours prior to starting treatment. Female patients of reproductive potential include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal (defined as amenorrhea >12 consecutive months; or women on hormone replacement therapy (HRT) with documented serum follicle stimulating hormone (FSH) level >35 mL.U/mL).
  • Female patients of reproductive potential or their partners must agree to use effective contraception while receiving trial treatment and for at least 3 months thereafter. The definition of effective contraception will be based on the judgment of the principal investigator or designated associate.
  • Inability or lack of willingness to comply with scheduled visits, treatment plans, protocol assessments or laboratory tests.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01737008

Contacts
Contact: Meghan Perry, B.Sc.Hons. 416-946-4501 ext 3181 meghan.perry@uhn.ca

Locations
Canada, Ontario
Princess Margaret Cancer Centre Recruiting
Toronto, Ontario, Canada, M5G 2M9
Principal Investigator: Lillian Siu, M.D.         
Sponsors and Collaborators
University Health Network, Toronto
Investigators
Principal Investigator: Lillian Siu, M.D. Princess Margaret Cancer Centre/University Health Network
  More Information

No publications provided

Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT01737008     History of Changes
Other Study ID Numbers: XDC-001
Study First Received: November 26, 2012
Last Updated: November 21, 2013
Health Authority: Canada: Ethics Review Committee
Canada: Health Canada

Keywords provided by University Health Network, Toronto:
Head and neck
Squamous cell carcinoma
Phase 1
Dacomitinib
Radiation
Radiotherapy
Chemotherapy
Chemoradiation
Chemoradiotherapy
Cisplatin
Pharmacokinetics
Maximum tolerated dose
Safety
Human epidermal growth factor receptor
Previously Untreated
Local or Locally Advanced

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on September 14, 2014