Weekly Oxaliplatin and Gemcitabine for Recurrent or Metastatic Head and Neck Cancer
Condition: Cancer of the Head and Neck
MeSH terms: Head and Neck Neoplasms
Intervention: Gemcitabine; Oxaliplatin
Intervention description: 1000 mg/m2 IV over 100 minutes Every 21 days; 65 mg/m2 IV over 120 minutes immediately following gemcitabine Every 21 days
Intervention MeSH terms: Gemcitabine; Oxaliplatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 8.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Cancer of the Head and Neck

Summary:

      The combination of oxaliplatin and gemcitabine is highly active in a wide variety of tumors
      including pancreatic, germ cell, breast, biliary, mesothelioma (Mitchell et al, 2002), and
      lung. In the last study which utilized days 1 and 8 gemcitabine 1000 mg/m2 and days 1 and 8
      oxaliplatin 65 mg/m2 in poor prognosis lung cancer patients (PS 1-3) the response rate was
      16% with no incidence of febrile neutropenia.

      Toxicity is a crucial consideration when designing regimens intended for palliation.
      Toxicities associated with cisplatin can make it difficult to use in patients with Head and
      Neck Cancer (HNC), many of whom are elderly and have comorbidities. In addition, many
      patients with metastatic HNC have previously received cisplatin during neoadjuvant/adjuvant
      therapy, or as part of their primary chemoradiation treatment. When these patients recur, it
      is possible their tumors have innate or acquired cisplatin resistance. Oxaliplatin is likely
      to be better tolerated than cisplatin containing regimens, especially with regards to
      neurotoxicity. Gemcitabine has shown promising activity as a single agent and in combination
      chemotherapy in the first line treatment of patients with HNC. A combination chemotherapy
      regimen using oxaliplatin and gemcitabine administered once every week is logical and worth
      exploring in patients with metastatic and recurrent head and neck cancer to improve the
      toxicity profile and patient monitoring while maintaining efficacy of the chemotherapy
      regimen.
    

Eligibility criteria:

        Inclusion Criteria:

          -  All patients must have histologically or cytologically confirmed diagnosis of squamous
             cell carcinoma of the head and neck region. Primary tumor sites include: lip, oral
             cavity, pharynx (oropharynx, hypopharynx), or larynx (supraglottis, glottis,
             subglottis). For nasopharynx primary, all squamous histologic subtypes are allowed
             (WHO type-I keratinizing, WHO type-II non-keratinizing, WHO type-III
             undifferentiated).

          -  Patients must have metastatic or locally recurrent carcinoma of the head and neck.
             Patients with locoregional disease must be considered incurable by means of
             locoregional therapy.

          -  All sites of disease must be assessed and designated as measurable or non-measurable
             disease as documented by CT, MRI, X-ray physical exam or nuclear exam. All measurable
             disease must be assessed within 28 days prior to registration. All non-measurable
             disease must be assessed within 42 days prior to registration.

          -  Patients may have received prior radiotherapy if there has been complete recovery from
             all radiation-induced toxicities. At least 4 weeks must have been elapsed from the
             completion of radiation therapy to the time of registration. If lesions within the
             radiation port are to be used to assess response to therapy, those lesions must have
             demonstrated clear progression following completion of radiation therapy.

          -  Patients must have adequate bone marrow reserve as documented by absolute neutrophil
             count (ANC) > 1,500 microliters and platelets > 100,000/microliter obtained within 14
             days prior to registration.

          -  Patients must have adequate hepatic as documented by serum bilirubin < 1.5 x the
             institutional upper limit of normal. Serum transaminase (SGOT or SGPT) must be < 1.5 x
             the institutional upper limit of normal serum unless the liver is involved with tumor,
             in which case serum transaminase (SGOT or SGPT) must be < 5 x the institutional limit
             of normal. These tests must be obtained within 14 days prior to registration.

          -  Patients must have a creatinine < 1.5 x the institutional upper limit of normal or a
             creatinine clearance of > 30 cc/min calculated using the following formula obtained
             within 28 days prior to registration.

        Calculated Creatinine Clearance = (140-age) X wt (kg) X (0.85 if female) 72 X creatinine
        (mg/dl)

        These tests must have been performed within 28 days prior to registration.

          -  All patients must be 18 years of age or older

          -  Patients must have a Zubrod performance of 0-2

        Exclusion Criteria:

          -  Patients must not have more than one prior chemotherapy regimen for
             recurrent/metastatic disease. Patients with initial locally advanced but
             non-metastatic disease are allowed to have one prior chemotherapy regimen as part of
             the primary curative therapy. All chemotherapy must be completed 4 weeks prior to
             registration. Any number of prior biologic therapies (e.g. chimeric antibodies or
             kinase inhibitors) is permitted as part of the chemotherapy regimen.

          -  Patients must not have a surgical treatment procedure for head and neck cancer within
             4 weeks prior to registration. Surgical procedure for biopsy purpose alone is allowed
             within 28 days prior to registration. Patients must have completely recovered from all
             surgery prior to registration.

          -  Patients must not have prior therapy with oxaliplatin or gemcitabine

          -  Patients with any evidence of active or uncontrolled infection, recent myocardial
             infection, unstable angina, or life threatening arrhythmia are not eligible.

          -  Patients with severe psychiatric disorder are not eligible.

          -  Patients with known brain metastasis are not eligible. However, brain-imaging studies
             are not required for eligibility if the patient has no neurological signs or symptoms.
             If brain-imaging studies are performed, they must be negative for disease.

          -  No other prior malignancy is allowed except for adequately treated basal cell or
             squamous cell carcinoma, in situ cervical cancer, or adequately treated Stage I and II
             cancer from which the patient is in complete remission, or any other malignancy from
             which the patient has been disease-free for 5 years.