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Paclitaxel, Cisplatin, and Cetuximab Followed By Cetuximab and 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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01084083
First received: March 9, 2010
Last updated: July 12, 2012
Last verified: October 2011

March 9, 2010
July 12, 2012
March 2010
March 2015   (final data collection date for primary outcome measure)
2-year progression-free survival [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01084083 on ClinicalTrials.gov Archive Site
  • Toxicity [ Designated as safety issue: Yes ]
  • Overall survival [ Designated as safety issue: No ]
  • Objective response [ Designated as safety issue: No ]
  • Quality of life as assessed at baseline and at 1, 6, 12, and 24 months after completion of study treatment [ Designated as safety issue: No ]
  • Correlative biomarker studies [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Paclitaxel, Cisplatin, and Cetuximab Followed By Cetuximab and 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
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

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.

OBJECTIVES:

Primary

  • To evaluate the efficacy of induction therapy comprising paclitaxel, cisplatin, and cetuximab followed by cetuximab in combination with low-dose or standard-dose intensity-modulated radiotherapy, as measured by 2-year progression-free survival (PFS), in patients with HPV-associated resectable stage III-IVB squamous cell carcinoma of the oropharynx.

Secondary

  • To assess overall survival.
  • To evaluate the objective response, local control, and metastatic rate.
  • To evaluate early and late toxicities of treatment.

Tertiary

  • To evaluate quality of life and speech and swallowing function as measured by FACT-G, FACT-HN, and VHNSS.
  • To assess the effect of treatment-induced fatigue on general physical functioning in patients with head and neck cancer.
  • To correlate functional decline with clinical, physical, and biologic correlatives.
  • To evaluate radiation-resistance markers, including ERCC1 single nucleotide polymorphism and protein expression, and to correlate them with treatment efficacy.
  • To demonstrate the usefulness of biomarkers, including ERCC1, EGFR, cytokine and chemokine markers, and plasma TGFA and TGFB levels, in predicting PFS and other outcome parameters.
  • To evaluate the correlation between the efficacy of cetuximab and polymorphisms in FcγR-receptors.
  • To evaluate functional outcome and biological parameters, including telomere length, angiotensin-converting enzyme polymorphism, and C-reactive protein level.

OUTLINE: This is a multicenter study.

  • Induction therapy: Patients receive cisplatin IV over 1 hour on day 1 and paclitaxel IV over 3 hours and cetuximab IV over 1-2 hours on days 1, 8, and 15. Treatment repeats every 21 days for 3 courses. Patients then undergo evaluation of response to induction therapy. Patients with a clinical complete response (CR) at the primary tumor site proceed to group 1 of concurrent radiotherapy and cetuximab. Patients with a clinical partial response (PR) or stable disease (SD) at the primary tumor site or those with grossly positive disease at the primary tumor site proceed to group 2 of concurrent radiotherapy and cetuximab.
  • Concurrent radiotherapy and cetuximab: Treatment begins 14-21 days after the last day of induction therapy.

    • Group 1 (CR): 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.
    • Group 2 (PR, SD, or grossly positive disease): 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.

Patients complete questionnaires assessing fatigue, physical function, weight loss, quality of life, head and neck symptom burden, and speech and swallowing function at baseline and at 1, 6, 12, and 24 months after completion of study treatment.

Tumor tissue and serum samples may be collected periodically for correlative laboratory studies.

After completion of study treatment, patients are followed up periodically for 3 years.

Interventional
Phase 2
Masking: Open Label
Primary Purpose: Treatment
  • Head and Neck Cancer
  • Precancerous Condition
  • Biological: cetuximab
    Given IV
  • Radiation: intensity-modulated radiation therapy
    Patients undergo low-dose radiotherapy
  • Experimental: Group 1
    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.
    Interventions:
    • Biological: cetuximab
    • Radiation: intensity-modulated radiation therapy
  • Experimental: Group 2
    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.
    Interventions:
    • Biological: cetuximab
    • Radiation: intensity-modulated radiation therapy
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
83
Not Provided
March 2015   (final data collection date for primary outcome measure)

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed squamous cell carcinoma of the oropharynx as determined by 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 (CT scan with IV contrast or 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 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

PATIENT CHARACTERISTICS:

  • ECOG 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
  • Not pregnant or nursing
  • 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:

    • NYHA class III-IV congestive heart failure
    • Cerebrovascular accident or transient ischemic attack
    • Unstable angina
    • Myocardial infarction (with or without ST elevation)
  • No uncontrolled diabetes, uncontrolled infection despite antibiotics, or uncontrolled hypertension within the past 30 days
  • No concurrent illness likely to interfere with study therapy or to prevent surgical resection
  • No prior severe infusion reaction to a monoclonal antibody

PRIOR CONCURRENT THERAPY:

  • No prior chemotherapy
  • No prior radiotherapy above the clavicles
  • No prior surgery with curative intent for this disease (complete head and neck exam with biopsy allowed)
  • No prior therapy specifically and directly targeting the EGFR pathway
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01084083
CDR0000665170, ECOG-E1308
Not Provided
Robert L. Comis, ECOG Group Chair's Office
Eastern Cooperative Oncology Group
National Cancer Institute (NCI)
Principal Investigator: Shanthi Marur, MD Sidney Kimmel Comprehensive Cancer Center
National Cancer Institute (NCI)
October 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP