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Induction Chemotherapy Followed By Cetuximab and Radiation in HPV-Associated Resectable Stage III/IV Oropharynx Cancer

This study has been completed.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier:
NCT01084083
First received: March 9, 2010
Last updated: September 22, 2015
Last verified: September 2015
  Purpose

RATIONALE: Drugs used in chemotherapy, such as paclitaxel and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Radiation therapy uses high energy x-rays to kill tumor cells. Giving paclitaxel, cisplatin, and cetuximab together with radiation therapy may kill more tumor cells.

PURPOSE: This phase II trial is studying paclitaxel, cisplatin, and cetuximab to see how well they work when followed by cetuximab and two different doses of intensity-modulated radiation therapy in treating patients with HPV-associated stage III or stage IV cancer of the oropharynx that can be removed by surgery.


Condition Intervention Phase
Head and Neck Cancer
Precancerous Condition
Biological: cetuximab
Radiation: intensity-modulated radiation therapy (IMRT)
Drug: Paclitaxel
Drug: Cisplatin
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Induction Chemotherapy Followed by Cetuximab (Erbitux) With Low Dose vs. Standard Dose IMRT in Patients With HPV-Associated Resectable Squamous Cell Carcinoma of the Oropharynx

Resource links provided by NLM:


Further study details as provided by Eastern Cooperative Oncology Group:

Primary Outcome Measures:
  • 24-month Progression-free Survival [ Time Frame: assessed within 14 days after delivery of the third cycle of induction therapy, and 8 weeks and 6 months after completion of concurrent therapy, then every 6 months until progression or until 3 years from study entry ] [ Designated as safety issue: No ]
    24-month progression-free survival is defined as the proportion of patients who were alive and progression-free at 24 months post registration. The primary study population for this endpoint is patients who were confirmed post-induction clinical complete response (CR) at their primary sites and subsequently received 5400 cGy radiation therapy to their primary sites.


Secondary Outcome Measures:
  • 24-months Overall Survival [ Time Frame: assessed within 14 days after delivery of the third cycle of induction therapy, and 8 weeks and 6 months after completion of concurrent therapy, then every 6 months until progression or until 3 years from study entry ] [ Designated as safety issue: No ]
    OS was defined as the time from registration to death, or censored at last date known alive. Kaplan-Meier method was used to estimate the overall survival rate at 24 months.

  • Primary Clinical Response Rate [ Time Frame: assessed within 14 days after delivery of the third cycle of induction therapy ] [ Designated as safety issue: No ]
    Primary clinical response rate is defined as the proportion of patients with complete response or partial response at their primary sites after induction therapy. Response status for the primary site was classified by clinical examination using endoscopy. If, however, the clinical response status of the primary was unclear based on endoscopy, then the CT or MRI (required at the end of induction) was used to determine status of the primary. If clinical and radiological evaluation of the primary was unclear, a biopsy was considered at the discretion of the treating physician.


Enrollment: 90
Study Start Date: March 2010
Study Completion Date: January 2015
Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1
After induction therapy with Paclitaxel and Cisplatin, patients undergo low-dose intensity-modulated radiotherapy (IMRT) 5 days per week for approximately 5 weeks (27 fractions). Patients also receive cetuximab IV over 1-2 hours once weekly for 6 weeks.
Biological: cetuximab
Given IV
Radiation: intensity-modulated radiation therapy (IMRT)
Patients undergo low-dose OR standard dose IMRT based on their clinical response to induction therapy
Drug: Paclitaxel
Given IV, 90 mg/m^2 on days 1, 8 and 15
Other Name: Abraxane, Taxol
Drug: Cisplatin
Given IV, 75 mg/m^2 on day 1
Other Name: Platinol
Experimental: Group 2
After induction therapy with Paclitaxel and Cisplatin, patients undergo standard-dose IMRT 5 days per week for approximately 6 weeks (33 fractions). Patients also receive cetuximab IV over 1-2 hours once weekly for 7 weeks.
Biological: cetuximab
Given IV
Radiation: intensity-modulated radiation therapy (IMRT)
Patients undergo low-dose OR standard dose IMRT based on their clinical response to induction therapy
Drug: Paclitaxel
Given IV, 90 mg/m^2 on days 1, 8 and 15
Other Name: Abraxane, Taxol
Drug: Cisplatin
Given IV, 75 mg/m^2 on day 1
Other Name: Platinol

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed squamous cell carcinoma of the oropharynx as determined by Hematoxylin and eosin (H&E) staining

    • Newly diagnosed disease
    • Resectable disease OR disease that is expected to become resectable after study treatment
    • Stage III, IVA, or IVB disease as determined by imaging studies (computed tomography (CT) scan with IV contrast or magnetic resonance imaging (MRI) required) and a complete head and neck exam
  • Paraffin-embedded tumor specimen available for central confirmation of HPV-associated disease as determined by H&E staining and in-situ hybridization (ISH) for HPV-16 and immunohistochemistry (IHC) for p16

    • HPV-associated disease is defined as p16 IHC-positive and/or HPV-16 ISH-positive
    • Non-HPV-associated disease is defined as p16 IHC-negative
    • NOTE: If there is limited tumor material, p16 IHC will be performed before HPV-16 ISH
  • Measurable disease of the primary tumor or nodes by clinical and radiographic methods, defined as a lesion that is ≥ 2 cm in at least one dimension by clinical exam AND by radiographic exam with CT scan or MRI (or a lesion that is ≥ 1 cm in at least one dimension if the radiographic exam utilizes spiral CT scan)
  • No primary tumor or nodal metastasis fixed to the carotid artery, skull base, or cervical spine
  • No evidence of distant metastases
  • Eastern Cooperative Oncology Group performance status 0-1
  • Granulocytes ≥ 1,000/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Total serum bilirubin ≤ 1.5 mg/dL
  • Creatinine clearance ≥ 60 mL/min
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No history of another malignancy (except for carcinoma in situ of the cervix and/or nonmelanomatous skin cancer) unless it has been curatively treated and the patient has been disease-free for ≥ 2 years
  • Patients with any of the following within the past 6 months are eligible provided they have been evaluated by a cardiologist and/or neurologist before study entry:

    • New York Heart Association (NYHA) class III-IV congestive heart failure
    • Cerebrovascular accident or transient ischemic attack
    • Unstable angina
    • Myocardial infarction (with or without ST elevation)

Exclusion Criteria:

  • Prior chemotherapy
  • Prior radiotherapy above the clavicles
  • Prior surgery with curative intent for this disease (complete head and neck exam with biopsy allowed)
  • Prior therapy specifically and directly targeting the EGFR pathway
  • Prior severe infusion reaction to a monoclonal antibody
  • Uncontrolled diabetes, uncontrolled infection despite antibiotics, or uncontrolled hypertension within the past 30 days
  • Concurrent illness likely to interfere with study therapy or to prevent surgical resection
  • Pregnant or nursing
  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: NCT01084083

  Show 121 Study Locations
Sponsors and Collaborators
Eastern Cooperative Oncology Group
National Cancer Institute (NCI)
Investigators
Principal Investigator: Shanthi Marur, MD Sidney Kimmel Comprehensive Cancer Center
  More Information

Publications:
Marur S, Lee JW, Cmelak A, et al.: ECOG 1308: A phase II trial of induction chemotherapy followed by cetuximab with low dose versus standard dose IMRT in patients with HPV-associated resectable squamous cell carcinoma of the oropharynx (OP). [Abstract] J Clin Oncol 30 (Suppl 15): A-5566, 2012.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier: NCT01084083     History of Changes
Other Study ID Numbers: CDR0000665170  ECOG-E1308  U10CA023318 
Study First Received: March 9, 2010
Results First Received: August 17, 2015
Last Updated: September 22, 2015
Health Authority: United States: Federal Government

Keywords provided by Eastern Cooperative Oncology Group:
human papilloma virus infection
stage III squamous cell carcinoma of the oropharynx
stage IV squamous cell carcinoma of the oropharynx
tongue cancer

Additional relevant MeSH terms:
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Precancerous Conditions
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site
Paclitaxel
Albumin-Bound Paclitaxel
Cetuximab
Cisplatin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on December 02, 2016