Pilot Study of Raltegravir and Cisplatin in Squamous Cell Carcinoma of Head and Neck

A Pilot Study of Raltegravir and Cisplatin in Squamous Cell Carcinoma of the 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 Overview

• Status: Completed
• Conditions: Head and Neck Cancer
• Intervention / Treatment: Drug: raltegravir and cisplatin

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • University of New Mexico Cancer Center

Participation Criteria

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:

• Histologic or cytologic diagnosis of squamous cell carcinoma of the head and neck. All primary sites are eligible, including keratinizing nasopharyngeal carcinoma (WHO grade 1 or 2) and carcinoma of unknown primary.
• Either the primary site or a metastatic locoregional tumor deposit (eg. lymph node, parotid gland, subcutaneous nodule) must be amenable to repeat, in-office biopsy by a head and neck surgeon.
• The patient must be considered an appropriate candidate for cisplatin chemotherapy by a medical oncologist. Acceptable indications include induction chemotherapy prior to surgery or radiation for localized disease, or palliative chemotherapy for advanced disease.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Adequate bone marrow function, defined as an absolute peripheral granulocyte count of greater than 1,500 cells/mm3 and platelet count greater than 100,000/mm3 and absence of a regular red blood cell transfusion requirement.
• Adequate hepatic function with a total bilirubin less than 2 mg/dl; SGOT and SGPT less than 1.5 times the upper limit of normal; alkaline phosphatase less than 2.5 times the upper limit of normal.
• Creatinine clearance greater than or equal to 55 mL/min. Creatinine clearance will be estimated by the Cockraft-Gault formula, using actual body weight.
• Women of childbearing potential must have a negative pregnancy test.
• Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment, and for at least 3 months thereafter.
• Age greater than 18.
• Able to provide written, informed consent.

Exclusion Criteria:

• No known brain metastases.
• Pregnant women or nursing mothers are not eligible for this trial.
• During the first two weekly cycles of cisplatin and raltegravir, patients may receive no other concurrent antineoplastic therapy, including chemotherapy, biologic agents or radiotherapy. For subsequent induction or palliative chemotherapy cycles, patients may receive combination cisplatin-docetaxel-raltegravir, on a three-week schedule as specified in this protocol.
• No severe medical problems, including unstable angina; myocardial infarction within the past 6 months; symptomatic congestive heart failure, NYHA grade II or higher; active infection requiring antibiotics.
• History of hypersensitivity reaction to cisplatin.
• Patient with known HIV disease.
• Any comorbid condition which would preclude full compliance with the protocol.
• Patient is less than 3 years free from another malignancy, except: a) if the other malignancy is non-melanomatous skin cancer or cervical carcinoma in situ or b) if the other primary malignancy is considered clinically insignificant and is requiring no active intervention.
• Peripheral neuropathy greater than or equal to grade 2.
• Ongoing treatment with rifampin, phenytoin, or phenobarbital.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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; Other Names: Isentress; Taxotere; cisplatin; MK-0518; raltegravir; docetaxel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gene expression modification	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.	3 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical activity	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.	2 to 6 months
Clinical toxicity	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	2 to 6 months
Progression free survival and overall survival	Progression-free and overall survival duration will be measured from entry into the protocol, until death.	2 years
Metnase expression	From biopsy materials, quantitative score generated by Aperio Scanning. Digital photomicrographs will be scored for frequency and intensity.	2 to 6 months

Collaborators and Investigators

• Sponsor: New Mexico Cancer Care Alliance
• Collaborators: American Cancer Society, Inc.
• Investigators: Principal Investigator: Houman Fekrazad, MD, University of New Mexico Cancer Center

Publications and helpful links

Helpful Links

• New Mexico Cancer Care Alliance
• UNM Cancer Center

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (ACTUAL): April 1, 2015
• Study Completion (ACTUAL): April 1, 2015

Study Registration Dates

• First Submitted: January 6, 2011
• First Submitted That Met QC Criteria: January 10, 2011
• First Posted (ESTIMATE): January 12, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): June 18, 2015
• Last Update Submitted That Met QC Criteria: June 16, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: HNSCC; SCC; head and neck; squamous cell; nasopharyngeal
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Squamous Cell; Carcinoma, Squamous Cell; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; HIV Integrase Inhibitors; Integrase Inhibitors; Docetaxel; Cisplatin; Raltegravir Potassium
• Other Study ID Numbers: INST 1012; NCI-2012-00914 (REGISTRY: NCI CTRP)