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

NCT01737008 | Completed Phase 1 DMC

• 1 other identifier: XDC-001
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Squamous Cell Carcinoma of the Head and Neck

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (in mg) of Dacomitinib

  1 year

• To preliminarily evaluate the response rate of the combination of Dacomitinib, Cisplatin and Radiation

  1 year

Secondary Outcomes (2)

• Levels of Dacomitinib in the Blood (Pharmacokinetics) in Combination with Cisplatin and Radiation

  Days 8, 22 and 43 (+2 day window) after initial dose

• Disease free survival, overall survival and locoregional and distant metastasis free survival

  6 and 12 months

Study Arms (2)

Dacomitinib with Radiotherapy

EXPERIMENTAL

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; Radiation: Radiotherapy

Dacomitinib and Chemoradiotherapy

EXPERIMENTAL

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; Radiation: Radiotherapy; Drug: Cisplatin

Interventions

dacomitinib DRUG

Tablets are administered orally or through a G-Tube, and can be taken with or without food.

Also known as: PF-00299804

Dacomitinib and Chemoradiotherapy; Dacomitinib with Radiotherapy

Radiotherapy RADIATION

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.

Dacomitinib and Chemoradiotherapy; Dacomitinib with Radiotherapy

Cisplatin DRUG

If selected for this arm, cisplatin will be administered intravenously every three weeks after receiving premedications.

Also known as: cisplatinum

Dacomitinib and Chemoradiotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (1)

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

Related Publications (1)

• Chiu JW, Chan K, Chen EX, Siu LL, Abdul Razak AR. Pharmacokinetic assessment of dacomitinib (pan-HER tyrosine kinase inhibitor) in patients with locally advanced head and neck squamous cell carcinoma (LA SCCHN) following administration through a gastrostomy feeding tube (GT). Invest New Drugs. 2015 Aug;33(4):895-900. doi: 10.1007/s10637-015-0245-3. Epub 2015 May 5.

  PMID: 25937431 DERIVED

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Carcinoma, Squamous Cell

Interventions

dacomitinib; Radiotherapy; Cisplatin

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms, Squamous Cell

Intervention Hierarchy (Ancestors)

Therapeutics; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Lillian Siu, M.D.

  Princess Margaret Cancer Centre/University Health Network

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 26, 2012
• First Posted: November 29, 2012
• Study Start: January 1, 2013
• Primary Completion: February 1, 2015
• Study Completion: May 1, 2015
• Last Updated: June 13, 2016

Record last verified: 2016-06

Locations

CA (1)