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

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified May 2007 by National Cancer Institute (NCI).
Recruitment status was:  Active, not recruiting
Sponsor:
ClinicalTrials.gov Identifier:
NCT00415298
First Posted: December 22, 2006
Last Update Posted: January 10, 2014
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
National Cancer Institute (NCI)
Information provided by:
National Cancer Institute (NCI)
  Purpose

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.


Condition Intervention
Head and Neck Cancer Drug: DACH polymer platinate AP5346 Drug: oxaliplatin Genetic: gene expression analysis Other: immunohistochemistry staining method Other: pharmacological study Procedure: biopsy

Study Type: Interventional
Study Design: Allocation: Randomized
Primary Purpose: Treatment
Official Title: AP5346 for Recurrent/Unresectable Squamous Cell Carcinoma of the Head and Neck: A Pilot Study With Clinical and Biological Endpoints

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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

Estimated Enrollment: 12
Study Start Date: May 2006
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.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00415298


Locations
United States, California
Moores UCSD Cancer Center
La Jolla, California, United States, 92093-0658
Sponsors and Collaborators
University of California, San Diego
National Cancer Institute (NCI)
Investigators
Study Chair: William L. Read, MD University of California, San Diego
  More Information

ClinicalTrials.gov Identifier: NCT00415298     History of Changes
Other Study ID Numbers: CDR0000520463
UCSD-HRPP-050275
First Submitted: December 20, 2006
First Posted: December 22, 2006
Last Update Posted: January 10, 2014
Last Verified: May 2007

Keywords provided by National Cancer Institute (NCI):
recurrent squamous cell carcinoma of the hypopharynx
recurrent squamous cell carcinoma of the larynx
recurrent squamous cell carcinoma of the lip and oral cavity
recurrent squamous cell carcinoma of the nasopharynx
recurrent squamous cell carcinoma of the oropharynx
stage III squamous cell carcinoma of the hypopharynx
stage III squamous cell carcinoma of the larynx
stage III squamous cell carcinoma of the lip and oral cavity
stage III squamous cell carcinoma of the nasopharynx
stage III squamous cell carcinoma of the oropharynx
stage IV squamous cell carcinoma of the hypopharynx
stage IV squamous cell carcinoma of the larynx
stage IV squamous cell carcinoma of the lip and oral cavity
stage IV squamous cell carcinoma of the nasopharynx
stage IV squamous cell carcinoma of the oropharynx

Additional relevant MeSH terms:
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site
Oxaliplatin
Antineoplastic Agents