Dose Escalation Trial of Neoadjuvant Sorafenib and Concurrent Sorafenib, Cisplatin and Radiation in Locally Advanced Squamous Cell Carcinomas of the Head and Neck (SCCHN)
Information source: British Columbia Cancer Agency
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Locally Advanced Squamous Cell Carcinomas of the Head and Neck (SCCHN)
Intervention: sorafenib (Drug); sorafenib (Drug); sorafenib and cisplatin (Drug); sorafenib and cisplatin (Drug); sorafenib and cisplatin (Drug)
Phase: Phase 1
Status: Withdrawn
Sponsored by: British Columbia Cancer Agency Official(s) and/or principal investigator(s): Stephen Chia, MD, Principal Investigator, Affiliation: British Columbia Cancer Agency
Summary
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.
Clinical Details
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)
Study design: Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label
Primary outcome: To assess the safety of neoadjuvant BAY 43-9006 (sorafenib) and concurrent BAY 43-9006 with radiation in a cohort of SCCHN
Secondary outcome: MTD Maximal tolerated dose
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
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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.
Locations and Contacts
BC Cancer Agency - Vancouver Centre, Vancouver, British Columbia V5Z 4E6, Canada
Additional Information
Last updated: November 3, 2010
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