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

Head and Neck Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00415298
• Other study ID #: CDR0000520463
• Secondary ID: UCSD-HRPP-050275
• Status: Active, not recruiting
• Phase: N/A
• First received: December 20, 2006
• Last updated: January 9, 2014
• Start date: May 2006

Study information

• Verified date: May 2007
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 12
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Squamous Cell
• Head and Neck Cancer
• Head and Neck Neoplasms

Intervention

Drug:
• DACH polymer platinate AP5346

• oxaliplatin

Genetic:
• gene expression analysis

Other:
• immunohistochemistry staining method

• pharmacological study

Procedure:
• biopsy

Locations

Country	Name	City	State
United States	Moores UCSD Cancer Center	La Jolla	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, San Diego	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Delivered-dose of platinum 24 hours after IV injection of a single dose of AP5346 vs a single dose of oxaliplatin			No
Primary	Correlation of platinum accumulation in the tumor and tumor DNA with clinical response			No
Primary	Correlation of platinum accumulation in the tumor and tumor DNA with molecular response as determined by GADD153 expression			No
Primary	Quantification of expression of CTR1, ATP7A, and ATP7B in squamous cell carcinoma of the head and neck (SCCHN) tumors by immunohistochemistry			No
Primary	Correlation of expression of CTR1, ATP7A, and ATP7B in SCCHN tumors with tumor platinum levels			No
Primary	Toxicity of AP5346			Yes