AP5346 or Oxaliplatin in Treating Patients With Metastatic and/or Unresectable Recurrent Head and Neck Cancer

January 9, 2014 updated by: University of California, San Diego

AP5346 for Recurrent/Unresectable Squamous Cell Carcinoma of the Head and Neck: A Pilot Study With Clinical and Biological Endpoints

RATIONALE: Drugs used in chemotherapy, such as AP5346 and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This randomized clinical trial is studying the dose of AP5346 to see how well it works compared with the dose of oxaliplatin in treating patients with metastatic and/or unresectable recurrent head and neck cancer.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • Compare the delivered-dose of platinum per gram of wet weight from a single dose of AP5346 vs a single dose of oxaliplatin in patients with metastatic and/or unresectable recurrent squamous cell carcinoma of the head and neck (SCCHN).
  • Correlate platinum accumulation in the tumor and tumor DNA with clinical response in patients treated with these regimens.
  • Correlate platinum accumulation in the tumor and tumor DNA with molecular tumor response as determined by GADD153 expression in patients treated with these regimens.
  • Quantify, by immunohistochemistry, the expression of the copper transporters CTR1, ATP7A, and ATP7B in SCCHN tumors and correlate expression of these transporters with tumor platinum levels.
  • Determine response in patients treated with AP5346.
  • Obtain additional data on the safety of AP5346 in these patients.

OUTLINE: This is a randomized, pilot study. Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive AP5346 IV over 2 hours three times daily on days 1 and 15.
  • Arm II: Patients receive a single dose of unmodified oxaliplatin IV over 2 hours on day 1.

Beginning on day 29, all patients may receive AP5346 as in arm I. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients undergo tumor biopsy before and 24 hours after the first course of treatment for correlative pharmacological, immunohistochemical (IHC), and molecular studies. Tumor specimens are assessed for platinum content, GADD153 gene expression (by molecular analysis), and copper transporter (CTR1, ATP7A, ATP7B) expression by IHC.

PROJECTED ACCRUAL: A total of 12 patients will be accrued for this study.

Study Type

Interventional

Enrollment (Anticipated)

12

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • La Jolla, California, United States, 92093-0658
        • Moores UCSD Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed primary squamous cell carcinoma of the head and neck, including the oral cavity, oropharynx, hypopharynx, larynx, or nasopharynx

    • Metastatic and/or unresectable locally recurrent disease for which no curative treatment is available

      • Patients must not be candidates for surgical resection or radiotherapy with curative intent
      • Histological documentation of relapse required, especially for locoregional recurrence or recurrence in a previously irradiated field

  • Tumor(s) must be amenable to minimally invasive biopsy during the first course of treatment

    • Must have evidence of progression or appearance of a new lesion after completion of radiotherapy, if biopsy site is in a previously irradiated field

PATIENT CHARACTERISTICS:

  • WHO performance status 0-2
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Absolute neutrophil count ≥ 2,000/mm³
  • Platelet count ≥ 100,000/mm³
  • Hemoglobin ≥ 10 g/dL
  • Bilirubin < 1.5 times upper level of normal (ULN)
  • Alkaline phosphatase (AP) ≤ 5 times normal (unless elevation is due to bone disease or bone metastasis in the absence of liver disease)

  • AST and ALT ≤ 3 times ULN

    • AST and ALT > 3 times ULN allowed provided AP ≤ 3 times ULN
  • Blood urea < 1.5 times ULN
  • Creatinine < 1.5 times ULN OR creatinine clearance > 60 mL/min OR creatinine clearance by 24-hour urine collection normal
  • Calcium normal
  • No history of hypersensitivity reactions of any kind to cisplatin or carboplatin
  • No other serious medical condition or psychiatric illness that would preclude the patient's ability to give informed consent or receive study treatment
  • No symptomatic peripheral neuropathy ≥ grade 2
  • No need for IV alimentation

  • No other serious illness or medical condition, including, but not limited to, the following:

    • Ongoing or active infection
    • Symptomatic congestive heart failure
    • Unstable angina pectoris or cardiac arrhythmia
    • Significant neurologic or psychiatric disorders, including dementia or uncontrolled seizures
    • Hypophosphatemia

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • At least 4 weeks since prior and no other concurrent anticancer treatment (i.e., chemotherapy, chemoradiotherapy, or radiotherapy)
  • At least 4 weeks since prior biologic therapy

  • No prior oxaliplatin

    • Prior cisplatin or carboplatin allowed
  • No concurrent anticoagulants other than cardioprotective doses of aspirin, cyclooxygenase 1-inhibitory nonspecific anti-inflammatory drugs, or prophylactic low-dose heparin
  • Concurrent bisphosphonates for hypercalcemia allowed provided the drug was initiated ≥ 3 months prior to study entry

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Delivered-dose of platinum 24 hours after IV injection of a single dose of AP5346 vs a single dose of oxaliplatin
Correlation of platinum accumulation in the tumor and tumor DNA with clinical response
Correlation of platinum accumulation in the tumor and tumor DNA with molecular response as determined by GADD153 expression
Quantification of expression of CTR1, ATP7A, and ATP7B in squamous cell carcinoma of the head and neck (SCCHN) tumors by immunohistochemistry
Correlation of expression of CTR1, ATP7A, and ATP7B in SCCHN tumors with tumor platinum levels
Toxicity of AP5346

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, San Diego

Collaborators

National Cancer Institute (NCI)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2006

Study Registration Dates

First Submitted

December 20, 2006

First Submitted That Met QC Criteria

December 20, 2006

First Posted (Estimate)

December 22, 2006

Study Record Updates

Last Update Posted (Estimate)

January 10, 2014

Last Update Submitted That Met QC Criteria

January 9, 2014

Last Verified

May 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000520463
  • UCSD-HRPP-050275

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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