NCT01275183

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
5

participants targeted

Target at below P25 for early_phase_1 head-and-neck-cancer

Timeline
Completed

Started Dec 2010

Longer than P75 for early_phase_1 head-and-neck-cancer

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

December 1, 2010

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

January 6, 2011

Completed
6 days until next milestone

First Posted

Study publicly available on registry

January 12, 2011

Completed
4.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2015

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2015

Completed
Last Updated

June 18, 2015

Status Verified

June 1, 2015

Enrollment Period

4.3 years

First QC Date

January 6, 2011

Last Update Submit

June 16, 2015

Conditions

Head and Neck Cancer

Keywords

HNSCCSCChead and necksquamous cellnasopharyngeal

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (4)

  • Clinical activity

    2 to 6 months

  • Clinical toxicity

    2 to 6 months

  • Progression free survival and overall survival

    2 years

  • Metnase expression

    2 to 6 months

Study Arms (1)

Raltegravir and cisplatin

EXPERIMENTAL
Drug: raltegravir and cisplatin

Interventions

raltegravir and cisplatinDRUG

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

Also known as: MK-0518, Isentress, raltegravir, cisplatin, docetaxel, Taxotere
Raltegravir and cisplatin

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of New Mexico Cancer Center

Albuquerque, New Mexico, 87106, United States

Location

Related Links

MeSH Terms

Conditions

Head and Neck NeoplasmsSquamous Cell Carcinoma of Head and Neck

Interventions

Raltegravir PotassiumCisplatinDocetaxel

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsCarcinoma, Squamous CellCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

PyrrolidinonesPyrrolidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsChlorine CompoundsInorganic ChemicalsNitrogen CompoundsPlatinum CompoundsTaxoidsCyclodecanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsDiterpenesTerpenes

Study Officials

  • Houman Fekrazad, MD

    University of New Mexico Cancer Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
early phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 6, 2011

First Posted

January 12, 2011

Study Start

December 1, 2010

Primary Completion

April 1, 2015

Study Completion

April 1, 2015

Last Updated

June 18, 2015

Record last verified: 2015-06

Locations

US(1)