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


N/A
18 Years
N/A
Open (Enrolling)
Both
Head and Neck Cancer

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Trial Information

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


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Primary Purpose: Treatment

Outcome Measure:

Delivered-dose of platinum 24 hours after IV injection of a single dose of AP5346 vs a single dose of oxaliplatin

Safety Issue:

No

Principal Investigator

William L. Read, MD

Investigator Role:

Study Chair

Investigator Affiliation:

University of California, San Diego

Authority:

United States: Federal Government

Study ID:

CDR0000520463

NCT ID:

NCT00415298

Start Date:

May 2006

Completion Date:

Related Keywords:

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

Name

Location

Moores UCSD Cancer CenterLa Jolla, California  92093-0658