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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
American Cancer Society, Inc.
Information provided by (Responsible Party):
New Mexico Cancer Care Alliance
ClinicalTrials.gov Identifier:
NCT01275183
First received: January 6, 2011
Last updated: August 13, 2013
Last verified: August 2013
  Purpose

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.


Condition Intervention Phase
Head and Neck Cancer
Drug: raltegravir and cisplatin
Phase 0

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by New Mexico Cancer Care Alliance:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 5
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)
Arms Assigned Interventions
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:
  • MK-0518
  • Isentress
  • raltegravir
  • cisplatin
  • docetaxel
  • Taxotere

  Eligibility

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

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.
  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: NCT01275183

Locations
United States, New Mexico
University of New Mexico Cancer Center
Albuquerque, New Mexico, United States, 87106
Sponsors and Collaborators
New Mexico Cancer Care Alliance
American Cancer Society, Inc.
Investigators
Principal Investigator: Houman Fekrazad, MD University of New Mexico Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: New Mexico Cancer Care Alliance
ClinicalTrials.gov Identifier: NCT01275183     History of Changes
Other Study ID Numbers: INST 1012, NCI-2012-00914
Study First Received: January 6, 2011
Last Updated: August 13, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by New Mexico Cancer Care Alliance:
HNSCC
SCC
head and neck
squamous cell
nasopharyngeal

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
Docetaxel
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 27, 2014