Dose Escalation Trial of Neoadjuvant Sorafenib and Concurrent Sorafenib, Cisplatin and Radiation in Locally Advanced Squamous Cell Carcinomas of the Head and Neck (SCCHN)

This study has been withdrawn prior to enrollment.
(Site decided not to open this study)
Sponsor:
Information provided by:
British Columbia Cancer Agency
ClinicalTrials.gov Identifier:
NCT00627835
First received: February 14, 2008
Last updated: November 3, 2010
Last verified: November 2010
  Purpose

The purpose of this study is to assess the safety and determine MTD (maximal tolerated doses) and recommended doses of neoadjuvant sorafenib (BAY 43-9006) and concurrent sorafenib, cisplatin and radiation in the locally advanced squamous cell carcinomas of the head and neck (SCCHN)patient population.


Condition Intervention Phase
Locally Advanced Squamous Cell Carcinomas of the Head and Neck (SCCHN)
Drug: sorafenib
Drug: sorafenib and cisplatin
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: A Phase I Dose Escalation Trial of Neoadjuvant Sorafenib and Concurrent Sorafenib, Cisplatin and Radiation in Locally Advanced Squamous Cell Carcinomas of the Head and Neck (SCCHN)

Resource links provided by NLM:


Further study details as provided by British Columbia Cancer Agency:

Primary Outcome Measures:
  • To assess the safety of neoadjuvant BAY 43-9006 (sorafenib) and concurrent BAY 43-9006 with radiation in a cohort of SCCHN [ Time Frame: ongoing ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • MTD Maximal tolerated dose [ Time Frame: ongoing ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 30
Arms Assigned Interventions
Experimental: Treatment Group 1: Cohort 1
Cohort 1 - sorafenib 200 mg PO bid concurrent with radiation
Drug: sorafenib
Cohort 1 - sorafenib 200 mg PO bid concurrent with radiation
Experimental: Treatment Group 1: sorafenib and radiation: Cohort 2
Cohort 2 - sorafenib 400 mg PO bid concurrent with radiation
Drug: sorafenib
o Cohort 2 - sorafenib 400 mg PO bid concurrent with radiation
Experimental: Treatment Group 2: Cohort 3
Cohort 3 - sorafenib 200 mg PO bid / cisplatin 75 mg/m2 weeks 1, 4 and 7
Drug: sorafenib and cisplatin
Cohort 3 - sorafenib 200 mg PO bid / cisplatin 75 mg/m2 weeks 1, 4 and 7
Experimental: Treatment Group 2: Cohort 4
o Cohort 4 - sorafenib 400 mg PO bid/ cisplatin 75 mg/m2 weeks 1, 4 and 7
Drug: sorafenib and cisplatin
o Cohort 4 - sorafenib 400 mg PO bid/ cisplatin 75 mg/m2 weeks 1, 4 and 7
Experimental: Treatment Group 2:Cohort 5
Cohort 5 - sorafenib 400 mg PO bid/ cisplatin 100 mg/m2 weeks 1, 4 and 7
Drug: sorafenib and cisplatin
Cohort 5 - sorafenib 400 mg PO bid/ cisplatin 100 mg/m2 weeks 1, 4 and 7

Detailed Description:

Squamous cell carcinoma of the head and neck is a relatively common malignancy in both Canada and the United States. Despite advancements made with the demonstration of improved outcomes for concurrent platinum based chemotherapy with radical radiation in locally advanced SCCHN, approximately 50% of cases will recur. The current treatment of locoregionally recurrent/metastatic SCCHN is palliative in intent, with a median survival in this population of 6-8 months. Thus improvements to the current backbone treatment of locally advanced SCCHN, that is platinum based chemotherapy with radical radiation, are desperately needed.

This is a non-randomized, open-label, phase I dose escalation trial of neoadjuvant Sorafenib and concurrent Sorafenib, Cisplatin and radiation in locally advanced squamous cell carcinomas of the head and neck (SCCHN).

  Eligibility

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

Inclusion Criteria:

Inclusion Criteria: Treatment Group 1 (Cohorts 1 & 2) - Radiation and Sorafenib Only.

  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 with radiation only.
  2. Stage III or IV disease (UICC/AJCC classification, 6th edition)
  3. Age ≥18
  4. Patients for whom concurrent cisplatinum is contraindicated due to poor patient tolerance (significant weight loss > 10% of body weight, mild renal dysfunction, ototoxicity, neuropathy, or age >70) yet deemed fit for radical radiation.
  5. Signed written consent.
  6. Availability for follow-up after treatment.
  7. If the patient is fertile he/she 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 2 weeks after therapy.
  8. Life expectancy greater than 6 months

Inclusion Criteria: Treatment group 2 (Cohorts 3 to 5) - Radiation, Sorafenib and Cisplatin.

  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.
  2. Stage III or IV disease (UICC/AJCC classification, 6th edition)
  3. Age ≥18.
  4. Signed written consent.
  5. Availability for follow-up after treatment.
  6. If the patient is fertile, he/she 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.
  7. Life expectancy greater than 6 months

Exclusion Criteria:

Treatment Group 1 (Cohorts 1 & 2) - Radiation and Sorafenib Only.

  1. ECOG performance status 3 or 4
  2. Absolute neutrophil count <1.0 X 109/L, platelet count <100 X 109/L or hemoglobin <90 g/L.
  3. Serum bilirubin ≥1.5 times ULN or AST/ALT ≥ 2.5 times ULN.
  4. Calculated creatinine clearance (Cockcroft-Gault) <40 mL/min. For patients in whom the calculated creatinine clearance is borderline, GFR may be estimated by nuclear renogram with the creatinine clearance ≥ 40 mL/min to be eligible.
  5. Uncontrolled hypertension despite adequate anti-hypertensive medications
  6. Bleeding diathesis
  7. Significant inter-current illness that will interfere with the radiation therapy during the trial such as HIV infection, pulmonary compromise, active significant alcohol abuse, active infection or febrile illness
  8. Any history of myocardial infarction, congestive heart failure (NY Heart Association Class 3 or 4), any history of ventricular arrhythmias, angina or active coronary heart disease within 6 months.
  9. Primary cancers of the nasal and paranasal cavities, and of the nasopharynx.
  10. Evidence of distant metastases. If based on the best available clinical evidence the investigator wishes to enroll the subject on trial, discussion and documentation with one of the principal investigators is required.
  11. Weight loss greater than 25% of usual body weight in the 3 months preceding trial entry.
  12. High risk for poor compliance with therapy or follow-up as assessed by investigator.
  13. Pregnant or lactating women.
  14. Prior radiation therapy to greater than 30% of the bone marrow
  15. Prior experimental therapy for cancer within 30 days of entering the trial.
  16. Prior radiation for head and neck cancer.
  17. 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.

Exclusion Criteria: Treatment group 2 (Cohorts 3 to 5) - Radiation, Sorafenib and Cisplatin.

  1. ECOG performance status 3 or 4
  2. Absolute neutrophil count <1.0 X 109/L, platelet count <100 X 109/L or hemoglobin <90 g/L.
  3. Serum bilirubin ≥1.5 times ULN or AST/ALT ≥ 2.5 times ULN.
  4. Calculated creatinine clearance (Cockcroft-Gault) <55 mL/min. For patients in whom the calculated creatinine clearance is borderline, GFR may be estimated by nuclear renogram with the creatinine clearance ≥ 55 mL/min to be eligible.
  5. Uncontrolled hypertension despite adequate anti-hypertensive medications
  6. Bleeding diathesis
  7. 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, active infection or febrile illness,
  8. 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.
  9. Primary cancers of the nasal and paranasal cavities, and of the nasopharynx.
  10. Evidence of distant metastases. If based on the best available clinical evidence the investigator wishes to enroll the subject on trial, discussion and documentation with one of the principal investigators is required.
  11. Symptomatic peripheral neuropathy ≥ grade 2.
  12. Clinically significant sensori-neural hearing impairment which may be exacerbated by cisplatin (audiometric abnormalities without corresponding clinical hearing impairment will not be grounds for exclusion)
  13. Weight loss greater than 20% of usual body weight in the 3 months preceding trial entry.
  14. High risk for poor compliance with therapy or follow-up as assessed by investigator.
  15. Pregnant or lactating women.
  16. Prior radiation therapy to greater than 30% of the bone marrow
  17. Prior experimental therapy for cancer within 30 days of entering the trial.
  18. Prior radiation for head and neck cancer.
  19. 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
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00627835

Locations
Canada, British Columbia
BC Cancer Agency - Vancouver Centre
Vancouver, British Columbia, Canada, V5Z 4E6
Sponsors and Collaborators
British Columbia Cancer Agency
Investigators
Principal Investigator: Stephen Chia, MD British Columbia Cancer Agency
  More Information

No publications provided

Responsible Party: Dr Stephen Chia, British Columbia Cancer Agency
ClinicalTrials.gov Identifier: NCT00627835     History of Changes
Other Study ID Numbers: OZM-003
Study First Received: February 14, 2008
Last Updated: November 3, 2010
Health Authority: Canada: Health Canada

Keywords provided by British Columbia Cancer Agency:
squamous cell carcinoma
head and neck
Neoadjuvant Sorafenib and Concurrent Sorafenib, Cisplatin and Radiation

Additional relevant MeSH terms:
Carcinoma, Squamous Cell
Carcinoma
Head and Neck Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site
Sorafenib
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014