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A Phase I Trial of Abraxane, Cisplatin and 5-Fluorouracil Along With Chemoradiotherapy in Advanced Head and Neck Cancer
This study is currently recruiting participants.
Verified by University Health Network, Toronto, August 2008
Sponsors and Collaborators: University Health Network, Toronto
Abraxis BioScience Inc.
Information provided by: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT00731380
  Purpose

The purpose of this study is to determine the highest dose of a ABI-007 that can be given with cisplatin and 5-fluorouracil without causing intolerable side effects in patients with advanced head and neck cancer.


Condition Intervention Phase
Head and Neck Cancer
Drug: ABI-007
Phase I

MedlinePlus related topics: Cancer Head and Neck Cancer
Drug Information available for: Carboplatin Cisplatin Paclitaxel Fluorouracil
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Single Group Assignment
Official Title: Phase I Trial of ABI-007 (Abraxane) Plus Cisplatin Plus 5-Fluorouracil (APF) as Induction Chemotherapy Followed by Concurrent Chemoradiotherapy in Patients With Locally Advanced Squamous Cell Cancers of the Head and Neck (HNSCC)

Further study details as provided by University Health Network, Toronto:

Primary Outcome Measures:
  • The maximum tolerated dose of ABI-007 with Cisplatin and 5-Fluorouracil (APF) [ Time Frame: two years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • safety and tolerability profiles for ABI-007 [ Time Frame: two years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 27
Study Start Date: July 2008
Estimated Study Completion Date: February 2011
Estimated Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: ABI-007
    Dose escalation beginning with ABI-007 75 mg/m2 day 1 + day 8, Cisplatin 100 mg/m2 day 1, 5-FU 1000 mg/m2/d continuous infusion x 96 hours on day 1-4, for 3 weeks x 3 cycles. Followed by Concurrent weekly Carboplatin (AUC 1.5) with radiotherapy for 7 weeks. Carboplatin should be given on Monday or Tuesday of each week, if possible.
Detailed Description:

Squamous cell carcinoma of the head and neck (HNSCC) is the 9th most common malignancy diagnosed in Canadians. In the year 2007, there was an estimated 4,350 new cases diagnosed in Canada, with approximately 1,600 deaths attributable to HNSCC[Canadian Cancer Statistics 2007]. In the United States there is an annual incidence of approximately 40,000 newly diagnosed cases of head and neck cancer [US Cancer Statistics 2006]. Primary treatment for newly diagnosed localized (stage I-II) HNSCC is surgery and/or radiotherapy. The majority of patients (70%) however present with locally advanced HNSCC (Stage III or IV). Treatment of locally advanced HNSCC generally consists of either concurrent chemotherapy and radiation or surgical resection followed by adjuvant radiation or adjuvant concurrent chemotherapy and radiation. Unfortunately despite aggressive treatment with combined modality therapies approximately 40-50% of cases recur, with the majority recurring at the primary site and/or regional nodes. Except for a small minority of patients in whom salvage surgery or radiotherapy can be delivered, the prognosis for the majority of these patients is poor and further treatment is generally considered palliative.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Previously untreated squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx. Histological or cytological confirmation is required. The disease must be considered to be potentially curable by combined chemoradiation. Patients with nasopharynx, paranasal sinus, skin or unknown primary sites are not eligible.
  2. Non-metastatic, stage III or IV disease (UICC/AJCC classification, 6th edition)
  3. Age ≥ 18.
  4. ECOG performance status of 0 or 1.
  5. Patients must have adequate hematological function:

    • absolute granulocyte count > 1.5 x 109/L
    • platelet count >100 x 109/L
    • hemoglobin > 90 g/L
  6. Must have adequate renal and hepatic function:

    • serum bilirubin < 1.5x UNL and AST/ALT <2.5x UNL
    • serum creatinine < 1.25 x UNL or a calculated creatinine clearance of > 60 ml/min
  7. Signed written consent.
  8. Availability for follow-up for up after treatment.
  9. The patient is fertile and is aware of the risk of becoming pregnant or fathering children and will use adequate contraception (oral contraception, IUD, diaphragm and spermicide or male condom and spermicide) throughout therapy and for at least 3 months after therapy.
  10. Life expectancy greater than 6 months

Exclusion Criteria:

  1. Significant inter-current illness that will interfere with the chemotherapy or radiation therapy during the trial such as HIV infection, cardiac insufficiency, pulmonary compromise, active significant alcohol abuse, uncontrolled psychotic disorder, active infection or febrile illness.
  2. Any history of myocardial infarction, any history of ventricular arrhythmias, angina or active coronary heart disease within 6 months. Significant cardiac disease resulting in an inability to tolerate the intravenous fluid load as required for administration of cisplatin.
  3. Evidence of distant metastases.
  4. Symptomatic peripheral neuropathy ≥ grade 1 by CTCAE v.3 criteria.
  5. Clinically significant sensorineural hearing impairment which may be exacerbated by cisplatin (audiometric abnormalities without corresponding clinical deafness will not be grounds for exclusion)
  6. Weight loss greater than 20% of usual body weight in the 3 months preceding trial entry.
  7. High risk for poor compliance with therapy or follow-up as assessed by investigator.
  8. Pregnant or lactating women.
  9. Prior radiation therapy to greater than 30% of the bone marrow
  10. Prior experimental therapy for cancer within 30 days of entering the trial.
  11. Prior radiation for head and neck cancer.
  12. Prior systemic chemotherapy for cancer.
  13. Patients with prior cancers, except: those diagnosed more than five years ago with no evidence of disease recurrence and a clinical expectation of recurrence of less than 5%; or successfully treated non-melanoma skin cancer; or carcinoma in situ of the cervix. However, any patient with previous invasive breast cancer, prostate cancer or melanoma is excluded.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00731380

Contacts
Contact: Lillian Siu, MD 416.946.2911 lillian.siu@uhn.on.ca
Contact: John Waldron, MD 416.946.4501 ext 6522 john.waldron@rmp.uhn.on.ca

Locations
Canada, Ontario
Princess Margaret Hospital Recruiting
Toronto, Ontario, Canada, M5G 3M9
Contact: Soo Chin, RN         soo.chin@uhn.on.ca    
Principal Investigator: Lillian Siu, MD            
Principal Investigator: John Waldron, MD            
Sponsors and Collaborators
University Health Network, Toronto
Abraxis BioScience Inc.
Investigators
Principal Investigator: Lillian Siu, MD University Health Network - Princess Margaret Hospital
  More Information

Responsible Party: University Health Network- Princess Margaret Hospital ( Drs. Lillian Siu and John Waldron )
Study ID Numbers: APF-001
Study First Received: August 6, 2008
Last Updated: August 8, 2008
ClinicalTrials.gov Identifier: NCT00731380  
Health Authority: Canada: Health Canada

Keywords provided by University Health Network, Toronto:
Abraxane
Head and Neck Cancer
Determine
Maximum
Tolerated dose
ABI-007
Combination
Cisplatin
5-Fluorouracil
Patients

Study placed in the following topic categories:
Epidermoid carcinoma
Cisplatin
Paclitaxel
Fluorouracil
Squamous cell carcinoma
Head and Neck Neoplasms
Carcinoma, squamous cell
Carboplatin
Carcinoma, Squamous Cell
Carcinoma, squamous cell of head and neck

Additional relevant MeSH terms:
Antimetabolites
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Mitosis Modulators
Physiological Effects of Drugs
Antimitotic Agents
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Neoplasms by Site
Radiation-Sensitizing Agents
Therapeutic Uses
Tubulin Modulators
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on January 16, 2009