Study of Olaparib With Radiation Therapy and Cetuximab in Advanced Head and Neck Cancer With Heavy Smoking History
This is a research study that plans to learn more about the safety and tolerability of an investigational drug called Olaparib, in combination with radiation therapy and cetuximab.
Hypothesis: Intensity modulated radiotherapy with concurrent C225 and Olaparib represents a feasible, biologically-based alternative to standard chemoradiation, with acceptable toxicity, for treatment of locally-advanced HNSCC in patients having a ≥ 10 pack-year smoking history.
Squamous Cell Carcinoma of the Head and Neck
Radiation: Radiation Therapy
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Trial of Olaparib (AZD2281) in Combination With C225 and Radiation Therapy in Patients With Locally Advanced, Stage IVA-B Squamous Cell Carcinomas of the Head/Neck With Heavy Smoking Histories|
- Maximum tolerated dose (MTD) of Olaparib [ Time Frame: 10 weeks from the start of protocol therapy ] [ Designated as safety issue: Yes ]Maximum tolerated dose (MTD) of Olaparib to be used for Phase II clinical testing.
|Study Start Date:||July 2012|
|Estimated Study Completion Date:||July 2017|
|Estimated Primary Completion Date:||July 2016 (Final data collection date for primary outcome measure)|
Experimental: Olaparib with C225 and Radiation Therapy
Patients will begin taking Olaparib at the assigned dose three days prior to their first Cetuximab infusion. Patients will receive an initial dose of Cetuximab, 400 mg/m², intravenously over 120 minutes on Day 1. The initial dose of C225 will precede the start of radiation by 5-7 days. All patients will receive RT to a total dose of 69.3 Gy in 33 fractions over 6½ weeks. Weekly C225 will be administered at 250 mg/m2 in combination with daily RT. Patients will be assigned to receive Olaparib (25, 50, 100 or 200 mg bid) in combination with RT and C225. Olaparib will be taken twice daily, beginning three days prior to first scheduled C225 infusion. A further dose level of 300mg or 400mg may be considered should the 200mg Olaparib dose be well tolerated in this C225/RT combination schedule.
Olaparib PO (25, 50, 100 or 200 mg bid) in combination with RT and C225. BID, beginning three days prior to first C225 infusion and discontinued after RT completed.
Other Name: AZD2281Drug: Cetuximab
Pre-RT cetuximab (C225), 400 mg/m²IV and weekly C225, 250 mg/m2 IV in during RT.
Other Name: ErbituxRadiation: Radiation Therapy
RT to a total dose of 69.3 Gy (primary tumor and involved lymph nodes) in 33 fractions over 6 and 1/2 weeks
Outcomes for heavy smokers with locally-advanced head and neck squamous cell cancer (HNSCC) treated with standard chemoradiation have been traditionally poor, suggesting a critical need for translation of novel biologically-based targeted approaches into clinical practice. In clinical trials, the Poly(ADP-ribose) polymerase-1 (PARP1) inhibitor Olaparib has been combined with other systemic agents, including paclitaxel, irinotecan, carboplatin and gemcitabine, in the treatment of patients with various solid tumors. Pre-clinical models have shown cooperative effects of combining PARP inhibition with radiation. A combined modality approach utilizing RT in combination with C225 and Olaparib after induction chemotherapy represents a rational, targeted approach for investigation in locally-advanced HNSCC patients.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01758731
|Contact: Robyn Swing||720-848-0607||Robyn.Swing@ucdenver.edu|
|United States, Colorado|
|University of Colorado Denver||Recruiting|
|Denver, Colorado, United States, 80045|
|Contact: Robyn Swing 720-848-0607 Robyn.Swing@ucdenver.edu|
|Principal Investigator: David Raben, M.D|
|Principal Investigator:||David Raben, M.D||University of Colorado, Denver|