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Trial of Induction Chemotherapy (ICT) Followed by Concurrent Chemoraditherapy (CR) With Monoclonal Antibody Cetuximab in Locally Advanced Head and Neck Squamous Cell Cancer

This study has been terminated.
(Principle Investigator left the institution.)
Sponsor:
Information provided by (Responsible Party):
Syed Jafri, Louisiana State University Health Sciences Center Shreveport
ClinicalTrials.gov Identifier:
NCT01326923
First received: March 24, 2011
Last updated: March 4, 2014
Last verified: March 2014
  Purpose

This is an open label, single arm Phase II study of induction chemotherapy followed by concurrent chemo-radiotherapy in patients with locally advanced head and neck squamous cell cancer (HNSCC) using monoclonal antibody cetuximab. Those patients with locally advanced HNSCC deemed to be candidates for definitive concurrent chemo-radiotherapy will be treated initially with 6 weeks of PCC (Paclitaxel, cetuximab and Carboplatin). This will be followed by a week of no treatment for interim evaluation, followed by definitive concurrent chemo-radiotherapy using 70Gy radiation with weekly cetuximab and cisplatin for 7 weeks. The hypothesis of the study is that the use of cetuximab during induction chemotherapy followed by cetuximab concurrent with chemoradiotherapy using low dose weekly cisplatin will improve local control as well as distant spread.


Condition Intervention Phase
Head and Neck Squamous Cell Cancer
Drug: Cetuximab
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Induction Chemotherapy (ICT) Followed by Concurrent Chemoraditherapy (CR) With Monoclonal Antibody Cetuximab in Locally Advanced Head and Nec Squamous Cell Cancer

Resource links provided by NLM:


Further study details as provided by Louisiana State University Health Sciences Center Shreveport:

Primary Outcome Measures:
  • Complete Response [ Time Frame: Analysis at Week 26 ] [ Designated as safety issue: No ]
    Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.


Secondary Outcome Measures:
  • Progression Free Survival [ Time Frame: Same as Primary Outcome Measure ] [ Designated as safety issue: No ]
    Improvement in progression free survival (PFS)in locally advanced stage III and IV head and neck cancer patients with sequential (ICT) followed by Concurrent chemo-radiotherapy (CR) using monoclonal antibody Cetuximab as compared to historical controls.


Enrollment: 7
Study Start Date: June 2010
Estimated Study Completion Date: June 2014
Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Single arm
Single arm phase II study
Drug: Cetuximab
Single arm phase II study of chemotherapy
Other Name: Single arm phase II study

Detailed Description:

Chemotherapy:

Chemotherapy would be used in two phases. In the initial phase all patients would be treated with ICT involving 6 cycles of PCC. This involves Cetuximab 400mg/m2 Week 1 and then 250mg/m2 weekly, Paclitaxel 80mg/m2 weekly and carboplatin AUC 2 weekly for 6 weeks followed by concurrent chemoradiotherapy with cetuximab. After ICT patients would be given weekly Cisplatin at 30mg/m2 and cetuximab at 250mg/m2 concurrent with radiation therapy.

Radiation Therapy:

Typically for tumors treated by megavoltage (6MV) radiotherapy alone or with chemotherapy, the primary tumor bed with an adequate margin and the draining lymphatics will be treated with parallel opposed lateral treatment portals; the lower neck node bearing area will be treated through an anterior port. The standard total dose for the targeted tumor bed and electively treated lymphatics is 50 Gy/25 fractions, and then, an additional boost dose to the neoplasm-bearing site(s) of 16 Gy to 20 Gy.

The total dose received by the spinal cord should not be allowed to exceed 46 Gy. For N1 to N3 disease, they also shall need a total dose (boost included) of 66 Gy and perhaps up to 70 Gy if it can be safely given 6.4 Study Outline:

  1. Patients who are deemed eligible and sign informed consent would be enrolled in the clinical trial.
  2. Prior to starting therapy staging PET/CT scan, medical history, physical exam, hematologic and biochemical testing will be undertaken.
  3. Since mucositis and oropharyngeal dysfunction is very likely with chemo-radiation PEG tube placements will be considered prior to treatment, in order to allow adequate nutrition in case of mucositis.
  4. Prior to starting radiation patients would undergo dental evaluation which is a standard practice.
  5. Patients would then undergo 6 weeks of ICT using PCC. Based on toxicity dose would be modified as described in section 8.
  6. For PCC regimen, cetuxmiab would be given first followed by paclitaxel and then carboplatin using standard pre-medication.
  7. A CT scan (no PET scan) of the head and neck will be performed during the evaluation Week 7 on any day of that week.
  8. Following induction chemotherapy patients would be treated with radiation therapy of up to 70 Gy concurrent with weekly Cisplatin at 30mg/m2 and cetuximab at 250mg/m2 for the duration of radiation therapy. Again dose modifications would be performed based as described in section 8.
  9. Cetuximab would be administered first followed by cisplatin concurrent with radiation.
  10. History and Physical examination would be performed at the end of treatment to document response and assess toxicity

10. Patient with residual disease at the primary site or neck after completion of chemoradiotherapy would be offered surgery.

11. Week 26 (3 months) after completion of radiation therapy a repeat PET scan will be performed to assess response which is standard of care.

12. After completion of all treatment patients will be followed at every 3 months interval to document relapse or manage toxicities from treatment.

  Eligibility

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

Inclusion Criteria:

  1. Adult patients 18 years and older with histologically proven locally advanced stage III or IV unresectable Squamous cell head and neck cancer SCCHN (including cancers of oral cavity, oropharynx, larynx and hypopharynx) with no evidence of distant metastasis
  2. A careful evaluation for resection is required from the surgeon and criteria for unresectability carefully defined for individual primary sites as follows:

    • Hypopharynx: The tumor must extend across the midline of the posterior pharyngeal wall or be fixed to the cervical spine
    • Larynx: There must by either direct extension into surrounding muscle or skin or greater than 3 cm of sub-glottic extension
    • Oral cavity: The lesion must be so extensive that a functional reconstruction is not possible.
    • Base of Tongue: The tumor must extend into the roof of tongue, or the patient must refuse a recommended total glossectomy
    • Tonsil: The tumor must extend into the pterygoid region as manifested by clinical trismus or demonstrated across the midline of the pharyngeal wall or directly into soft tissue of the neck
    • Patients with neck lymph node metastases fixed to the carotid artery, the mastoid, the base of the skull, or the cervical spine are considered un-resectable
    • Medical unsuitability for resection is not sufficient for patient eligibility
    • Patient's refusal for surgery except in case of total glossectomy is not considered a reason for unresectibility
  3. Patients must have received no prior treatment for head and neck cancer
  4. ECOG Performance status 0-1
  5. Adequate organ function (All labs should be obtained within 14 days prior to start of study drug treatment)

    • leukocytes > 3,000/mcL
    • absolute neutrophil count > 1,500/mcL
    • platelets > 100,000/mcL
    • total Bilirubin within normal institutional limits
    • AST (SGOT)/ALT(SGPT) < 2.5 X institutional upper limit of normal
    • creatinine within normal institutional limits or creatinine clearance > 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
  6. Ability to give informed consent and willingness to adhere to study protocol
  7. Subjects of reproductive potential must agree to follow accepted birth control methods during treatment and for 12 months after completion of treatment. Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study

Exclusion Criteria:

  1. Patient who have had prior treatment for head and neck cancer
  2. Prior history of radiation to head and neck area
  3. Known malignancy other than the current cancer
  4. Uncontrolled intercurrent illness including but not limited to ongoing active infection, history of cardiac disease, e.g. uncontrolled hypertension, unstable angina, congestive heart failure, myocardial infarction within last six months or ventricular arrhythmias requiring medication, psychiatric illness that would impair patients ability to comply with study requirements
  5. Pregnant or lactating women (any women becoming pregnant during the study will be withdrawn from the study)
  6. Patient with documented or symptoms of peripheral neuropathy
  7. History of allergic reaction to compounds similar to the ones used in this study
  8. Any condition that would hamper ability to give informed consent or ability to comply with study protocol
  9. HIV patients on anti-retroviral therapy are in-eligible to participate in this study because of potential interaction with the study drugs and increase susceptibility for infections during course of marrow suppressive chemotherapy and radiotherapy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01326923

Locations
United States, Louisiana
LSU Health Sciences Center
Shreveport, Louisiana, United States, 71103
Sponsors and Collaborators
Louisiana State University Health Sciences Center Shreveport
Investigators
Principal Investigator: Syed H Jafri, MB,B,S LSU shreveport
  More Information

No publications provided

Responsible Party: Syed Jafri, Associate Professor, Louisiana State University Health Sciences Center Shreveport
ClinicalTrials.gov Identifier: NCT01326923     History of Changes
Other Study ID Numbers: H10-109
Study First Received: March 24, 2011
Last Updated: March 4, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Louisiana State University Health Sciences Center Shreveport:
Head
Neck
Locally advanced
Squamous Cell
Hypopharynx
Larynx
Oral Cavity
Base of Tongue
Tonsil
Neck lymph node
Resection

Additional relevant MeSH terms:
Carcinoma, Squamous Cell
Neoplasms, Squamous Cell
Carcinoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Antibodies, Monoclonal
Cetuximab
Antineoplastic Agents
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014