Pilot Study of Raltegravir and Cisplatin in Squamous Cell Carcinoma of Head and Neck
The proposed study is a first-in-human pilot of a novel anti-cancer strategy: Metnase inhibition to potentiate DNA damaging chemotherapy. The investigators will conduct serial tumor biopsies in subjects with HNSCC at three timepoints: baseline, after cisplatin, and after cisplatin-raltegravir. The investigators will investigate immunohistochemical expression changes of γH2AX, Chk2, and Annexin V, three biomarkers of DNA damage and apoptosis. The study is designed to identify an intermediate signal of the potentiation of cisplatin chemotherapy by raltegravir in HNSCC, which will justify a future phase I/II study.
|Study Design:||Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Pilot Study of Raltegravir and Cisplatin in Squamous Cell Carcinoma of the Head and Neck|
- Gene expression modification [ Time Frame: 3 weeks ] [ Designated as safety issue: No ]Expression changes of three selected tumor biomarkers (DNA damage and apoptosis) will be measured at baseline, after cisplatin alone, and after raltegravir-cisplatin. Tumor biomarkers include pChk2, Annexin V, and metnase.
- Clinical activity [ Time Frame: 2 to 6 months ] [ Designated as safety issue: No ]
Preliminary clinical activity of the combination of raltegravir and cisplatin-based chemotherapy in HNSCC will be measured by RECIST criteria. Patients who elect participation in Part 2 will undergo tumor response assessment in accordance with RECIST 1.1 criteria after every 3 cycles of cisplatin-docetaxel-raltegravir. Response rate after 3 cycles will be reported as applicable.
Preliminary toxicity of the combination of raltegravir and cisplatin-based chemotherapy in HNSCC as measured by the grading system (0-4) of the NCI CTCAE v.4
Baseline Metnase expression in HNSCC.
- Clinical toxicity [ Time Frame: 2 to 6 months ] [ Designated as safety issue: Yes ]Preliminary toxicity of the combination of raltegravir and cisplatin-based chemotherapy in HNSCC as measured by the grading system (0-4) of the NCI CTCAE v.4
- Progression free survival and overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]Progression-free and overall survival duration will be measured from entry into the protocol, until death.
- Metnase expression [ Time Frame: 2 to 6 months ] [ Designated as safety issue: No ]From biopsy materials, quantitative score generated by Aperio Scanning. Digital photomicrographs will be scored for frequency and intensity.
|Study Start Date:||December 2010|
|Estimated Study Completion Date:||December 2014|
|Estimated Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
|Experimental: Raltegravir and cisplatin||
Drug: raltegravir and cisplatin
Cisplatin, intravenous, 30 mg/m2, days 2 and 16, 1 to 2 hours
Raltegravir, oral,400 mg, twice per day, days 1 through 5 or days 15 to 19
Part 2 (optional): Docetaxel, intravenous, 75 mg/M2, day 2, every 21 days, 3 to 6 cycles
Part 2 (optional): Cisplatin, intravenous, 75 mg/M2, day 2, every 21 days, 3 to 6 cycles
Part 2: (optional): Raltegavir, oral, 400 mg, twice per day, days 1 through 5, 3 to 6 cycles
Please refer to this study by its ClinicalTrials.gov identifier: NCT01275183
|United States, New Mexico|
|University of New Mexico Cancer Center|
|Albuquerque, New Mexico, United States, 87106|
|Principal Investigator:||Houman Fekrazad, MD||University of New Mexico Cancer Center|