Radiation Therapy With Cisplatin, Docetaxel, or Cetuximab After Surgery in Treating Patients With Stage III-IV Squamous Cell Head and Neck Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Radiation Therapy Oncology Group
Sponsor:
Collaborators:
NRG Oncology Foundation, Inc.
Information provided by (Responsible Party):
Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:
NCT01810913
First received: March 12, 2013
Last updated: July 10, 2014
Last verified: July 2014
  Purpose

This randomized phase II/III trial studies how well radiation therapy works when given together with cisplatin compared to docetaxel or cetuximab and docetaxel after surgery in treating patients with stage III-IV squamous cell head and neck cancer. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Drugs used in chemotherapy, such as cisplatin and docetaxel, 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 transmit tumor killing molecules to them. It is not yet known whether radiation therapy is more effective when given with cisplatin, docetaxel, or cetuximab and docetaxel.


Condition Intervention Phase
Stage III Squamous Cell Carcinoma of the Hypopharynx
Stage III Squamous Cell Carcinoma of the Larynx
Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity
Stage III Squamous Cell Carcinoma of the Oropharynx
Stage III Verrucous Carcinoma of the Larynx
Stage III Verrucous Carcinoma of the Oral Cavity
Stage IV Squamous Cell Carcinoma of the Hypopharynx
Stage IVA Squamous Cell Carcinoma of the Larynx
Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity
Stage IVA Squamous Cell Carcinoma of the Oropharynx
Stage IVA Verrucous Carcinoma of the Larynx
Stage IVA Verrucous Carcinoma of the Oral Cavity
Stage IVB Squamous Cell Carcinoma of the Larynx
Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity
Stage IVB Squamous Cell Carcinoma of the Oropharynx
Stage IVB Verrucous Carcinoma of the Larynx
Stage IVB Verrucous Carcinoma of the Oral Cavity
Tongue Cancer
Drug: cisplatin
Drug: docetaxel
Biological: cetuximab
Other: laboratory biomarker analysis
Procedure: quality-of-life assessment
Radiation: intensity-modulated radiation therapy
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Phase II/III Trial of Surgery and Postoperative Radiation Delivered With Concurrent Cisplatin Versus Docetaxel Versus Docetaxel and Cetuximab for High-Risk Squamous Cell Cancer of the Head and Neck

Resource links provided by NLM:


Further study details as provided by Radiation Therapy Oncology Group:

Primary Outcome Measures:
  • Disease-free survival (DFS) (Phase II) [ Time Frame: From randomization to date of failure (local, regional or distant progression or death) or last follow-up. Analysis occurs after 56 failures have been reported for each pairwise comparison. ] [ Designated as safety issue: No ]
    Estimated using the Kaplan-Meier method for each arm. Their distributions will be compared between treatment arms with a one-sided log rank test.

  • Overall survival (OS) (Phase III) [ Time Frame: From randomization to date of failure (death) or last follow-up. Analysis occurs after 183 failures have been reported. ] [ Designated as safety issue: No ]
    Estimated using the Kaplan-Meier method for each arm. Their distributions will be compared between treatment arms with a one-sided log rank test.


Secondary Outcome Measures:
  • Local-regional failure (LRF) [ Time Frame: From randomization to date of failure (local or regional progression) or distant progression or death or last follow-up. Analysis occurs at hte same time as the primary outcome. ] [ Designated as safety issue: No ]
    The cumulative incidence method will be used to estimate LRF and DM rates. Multivariate analysis will be performed using the Cox proportional hazards model.

  • Distant metastasis (DM) [ Time Frame: From randomization to date of failure (distant progression) or local or regional progression or death or last follow-up. Analysis occurs at the same time as the primary outcome. ] [ Designated as safety issue: No ]
    The cumulative incidence method will be used to estimate LRF and DM rates. Multivariate analysis will be performed using the Cox proportional hazards model.

  • Patterns of cancer failure (local, regional, distant) [ Time Frame: From randomization to date of local, regional or distant progression or death or last follow-up. Analysis occurs at the same time as the primary outcome. ] [ Designated as safety issue: No ]
  • Acute toxicity profiles during and at completion of treatment, graded according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0 [ Time Frame: Up to 7 weeks ] [ Designated as safety issue: Yes ]
    These rates will be estimated using a binomial distribution along with their associated 95% confidence intervals and will be compared using Fisher's exact test between the treatment arms.

  • Late toxicity profiles, graded according to the NCI CTCAE version 4.0 [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    These rates will be estimated using a binomial distribution along with their associated 95% confidence intervals and will be compared using Fisher's exact test between the treatment arms.

  • Functional Assessment of Cancer Therapy-Head & Neck (FACT-H&N) scores [ Time Frame: Up to 12 months after completion of RT ] [ Designated as safety issue: No ]
    The effect of acute mucosal toxicity on swallowing dysfunction and global QOL will be modeled using general linear regression. Binary outcomes will be compared using Fisher's Exact test and modeled using logistic regression. The mean change from completion of chemoradiation at each time point will be summarized using mean and standard deviations for each arm. Overall score and mean change from completion of chemoradiation will be compared between the arms using a two sample t test. If data normality assumptions are not met, the Wilcoxon rank sum test will be used to test the hypothesis. Mean change from completion of chemoradiation will be tested using an omnibus F test followed by individual comparisons of change scores at different time points within each treatment group.

  • MD Anderson Symptom Inventory - Head & Neck (MDASI-HN) scores [ Time Frame: Up to 24 months after completion of RT ] [ Designated as safety issue: No ]
    The effect of acute mucosal toxicity on swallowing dysfunction and global QOL will be modeled using general linear regression. Binary outcomes will be compared using Fisher's Exact test and modeled using logistic regression. The mean change from completion of chemoradiation at each time point will be summarized using mean and standard deviations for each arm. Overall score and mean change from completion of chemoradiation will be compared between the arms using a two sample t test. If data normality assumptions are not met, the Wilcoxon rank sum test will be used to test the hypothesis. Mean change from completion of chemoradiation will be tested using an omnibus F test followed by individual comparisons of change scores at different time points within each treatment group.

  • MD Anderson Dysphagia Inventory (MDADI) scores [ Time Frame: Up to 24 months after completion of RT ] [ Designated as safety issue: No ]
    The effect of acute mucosal toxicity on swallowing dysfunction and global QOL will be modeled using general linear regression. Binary outcomes will be compared using Fisher's Exact test and modeled using logistic regression. The mean change from completion of chemoradiation at each time point will be summarized using mean and standard deviations for each arm. Overall score and mean change from completion of chemoradiation will be compared between the arms using a two sample t test. If data normality assumptions are not met, the Wilcoxon rank sum test will be used to test the hypothesis. Mean change from completion of chemoradiation will be tested using an omnibus F test followed by individual comparisons of change scores at different time points within each treatment group.

  • EuroQol (EQ-5D) scores [ Time Frame: Up to 24 months after completion of RT ] [ Designated as safety issue: No ]
    The effect of acute mucosal toxicity on swallowing dysfunction and global QOL will be modeled using general linear regression. Binary outcomes will be compared using Fisher's Exact test and modeled using logistic regression. The mean change from completion of chemoradiation at each time point will be summarized using mean and standard deviations for each arm. Overall score and mean change from completion of chemoradiation will be compared between the arms using a two sample t test. If data normality assumptions are not met, the Wilcoxon rank sum test will be used to test the hypothesis. Mean change from completion of chemoradiation will be tested using an omnibus F test followed by individual comparisons of change scores at different time points within each treatment group.

  • Quality adjusted life year (QALY) [ Time Frame: From randomization to date of death or last follow-up. ] [ Designated as safety issue: No ]
    Quality-adjusted survival will be compared using a two-sample independent t test. If data normality assumptions are not met, the Wilcoxon rank sum test will be used to test the hypothesis.

  • Translational research analysis [ Time Frame: From randomization to date of death or last follow-up. ] [ Designated as safety issue: No ]

Estimated Enrollment: 675
Study Start Date: March 2013
Estimated Primary Completion Date: May 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1 (IMRT, cisplatin)
Patients undergo IMRT QD five days a week and receive cisplatin IV over 1-2 hours once weekly for 6 weeks.
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Other: laboratory biomarker analysis
Correlative studies
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Radiation: intensity-modulated radiation therapy
Undergo IMRT
Other Name: IMRT
Experimental: Arm 2 (IMRT, docetaxel)
Patients undergo IMRT as in Arm I and receive docetaxel IV once weekly for 6 weeks.
Drug: docetaxel
Given IV
Other Names:
  • RP 56976
  • Taxotere
  • TXT
Other: laboratory biomarker analysis
Correlative studies
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Radiation: intensity-modulated radiation therapy
Undergo IMRT
Other Name: IMRT
Experimental: Arm 3 (IMRT, docetaxel, cetuximab)
Patients receive cetuximab IV over 120 minutes on week 1 and over 60 minutes once weekly on weeks 2-7. Patients undergo IMRT as in Arm I and receive docetaxel once weekly for 6 weeks.
Drug: docetaxel
Given IV
Other Names:
  • RP 56976
  • Taxotere
  • TXT
Biological: cetuximab
Given IV
Other Names:
  • C225
  • C225 monoclonal antibody
  • IMC-C225
  • MOAB C225
  • monoclonal antibody C225
Other: laboratory biomarker analysis
Correlative studies
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Radiation: intensity-modulated radiation therapy
Undergo IMRT
Other Name: IMRT

Detailed Description:

PRIMARY OBJECTIVES:

I. To select the better experimental arm to improve disease-free survival (DFS) over the control arm of radiation and cisplatin. (Phase II) II. To determine whether the selected experimental arm will improve overall survival (OS) over the control arm of radiation and cisplatin. (Phase III)

SECONDARY OBJECTIVES:

I. To improve local-regional disease control. II. To compare distant metastasis. III. To compare patterns of cancer failure (local, regional, distant) and correlate with radiation dose and technique.

IV. To compare acute toxicity profiles during radiation therapy (RT) and at completion of treatment.

V. To compare late toxicity profiles at 1, 3, and 5 years after treatment. VI. To compare overall quality of life. VII. To compare patient-reported outcome. VIII. To compare swallowing function at 1 and 2 years. IX. To investigate associations between acute mucosal toxicity, swallowing function, and quality of life (QOL).

X. To compare quality adjusted life years (QALY). XI. To investigate associations between late toxicity (dysphagia) and QALY. XII. To determine whether specific molecular profiles are associated with clinical outcomes.

OUTLINE: Patients are randomized to 1 of 3 treatment groups.

ARM 1: Patients undergo intensity modulated radiation therapy (IMRT) once daily (QD) five days a week and receive cisplatin intravenously (IV) over 1-2 hours once weekly for 6 weeks.

ARM 2: Patients undergo IMRT as in Arm I and receive docetaxel IV once weekly for 6 weeks.

ARM 3: Patients receive cetuximab IV over 120 minutes on week 1 and over 60 minutes once weekly on weeks 2-7. Patients undergo IMRT as in Arm I and receive docetaxel once weekly for 6 weeks.

After completion of study treatment, patients are followed up at 1 and 3 months, every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

  Eligibility

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

Inclusion Criteria:

  • Pathologically (histologically or cytologically) proven diagnosis of head and neck squamous cell carcinoma (HNSCC) involving the oral cavity, oropharynx (p16 negative), larynx, or hypopharynx within 63 days of registration
  • Patients must have undergone gross total surgical resection of high-risk oral cavity, oropharynx (p16 negative), larynx, or hypopharynx within 63 days prior to registration
  • Patients must have at least 1 of the following high-risk pathologic features: extracapsular nodal extension or invasive cancer seen within 3 mm of the primary tumor resection margins
  • Pathologic stage III or IV head and neck squamous cell carcinoma (HNSCC), including no distant metastases, based upon the following minimum diagnostic workup:

    • General history and physical examination by a radiation oncologist and/or medical oncologist within 84 days prior to registration;
    • Examination by an ear nose throat (ENT) or head & neck surgeon prior to surgery; a laryngopharyngoscopy (mirror and/or fiber optic and/or direct procedure), if appropriate is recommended but not required. Intra-operative examination is acceptable documentation.
    • Pre-op Imaging: Either a computed tomography (CT) (with contrast) or CT/positron emission tomography (PET) and/or an magnetic resonance imaging (MRI) (T1 with gadolinium and T2) of the neck within 84 days prior to surgery; note: this imaging data (diagnostic pre-operative scan showing gross disease) is to be submitted in Digital Imaging and Communications in Medicine (DICOM) format via TRIAD; the report is to be uploaded into Rave
    • Chest CT scan (with or without contrast) or CT/PET of chest (with or without contrast) within 84 days prior to registration
  • Zubrod performance status of 0-1 within 14 days prior to registration
  • Absolute granulocyte count (AGC) >= 1,500 cells/mm^3
  • Platelets >= 100,000 cells/mm^3
  • Hemoglobin >= 8.0 g/dl (Note: The use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 8.0 g/dl is acceptable)
  • Total bilirubin < 2 x institutional upper limit of normal (ULN) within 14 days prior to registration
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 3 x institutional ULN within 14 days prior to registration
  • Serum creatinine institutional ULN within 14 days prior to registration or; creatinine clearance (CC) >= 50 ml/min within 14 days prior to registration determined by 24-hour collection or estimated by Cockcroft-Gault formula
  • Negative serum or urine pregnancy test within 14 days prior to registration for women of childbearing potential
  • The following assessments are required within 14 days prior to registration: sodium (Na), potassium (K), chloride (Cl), glucose, calcium (Ca), magnesium (Mg), and albumin; Note: Patients with an initial magnesium < 0.5 mmol/L (1.2 mg/dl) may receive corrective magnesium supplementation but should continue to receive either prophylactic weekly infusion of magnesium and/or oral magnesium supplementation (eg, magnesium oxide) at the investigator's discretion
  • Patients with feeding tubes are eligible for the study
  • Women of childbearing potential and male participants who are sexually active must agree to use a medically effective means of birth control
  • Patient must provide study specific informed consent prior to study entry, including consent for mandatory tissue submission for epidermal growth factor receptor (EGFR) analysis and for oropharyngeal cancer patients, human papilloma virus (HPV) analysis

Exclusion Criteria:

  • Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 1095 days (3 years); noninvasive cancers (for example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible) are permitted even if diagnosed and treated < 3 years ago
  • Patients with simultaneous primaries or bilateral tumors are excluded, with the exception of patients with bilateral tonsil cancers or patients with T1-2, N0, M0 resected differentiated thyroid carcinoma, who are eligible
  • Prior systemic chemotherapy or anti-epidermal growth factor (EGF) therapy for the study cancer; note that prior chemotherapy for a different cancer is allowable
  • Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
  • Severe, active co-morbidity, defined as follows:

    • Unstable angina and/or congestive heart failure requiring hospitalization within 6 months prior to registration
    • Transmural myocardial infarction within 6 months prior to registration
    • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
    • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
    • Idiopathic pulmonary fibrosis or other severe interstitial lung disease that requires oxygen therapy or is thought to require oxygen therapy within 1 year prior to registration
    • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for coagulation parameters are not required for entry into this protocol
    • Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease and Control (CDC) definition; note: HIV testing is not required for entry into this protocol; the need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive; protocol-specific requirements may also exclude immuno-compromised patients
  • Grade 3-4 electrolyte abnormalities (Common Terminology Criteria for Adverse Events [CTCAE], v. 4):
  • Serum calcium (ionized or adjusted for albumin) < 7 mg/dl (1.75 mmol/L) or > 12.5 mg/dl (> 3.1 mmol/L) despite intervention to normalize levels
  • Glucose < 40 mg/dl (< 2.2 mmol/L) or > 250 mg/dl (> 14mmol/L)
  • Magnesium < 0.9 mg/dl (< 0.4 mmol/L) or > 3 mg/dl (> 1.23 mmol/L) despite intervention to normalize levels
  • Potassium < 3.5 mmol/L or > 6 mmol/L despite intervention to normalize levels
  • Sodium < 130 mmol/L or > 155 mmol/L despite intervention to normalize levels
  • Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic
  • Prior allergic reaction to cetuximab
  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: NCT01810913

  Show 24 Study Locations
Sponsors and Collaborators
Radiation Therapy Oncology Group
NRG Oncology Foundation, Inc.
Investigators
Principal Investigator: Paul Harari Radiation Therapy Oncology Group
  More Information

No publications provided

Responsible Party: Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT01810913     History of Changes
Other Study ID Numbers: RTOG 1216, NCI-2013-00500, U10CA021661
Study First Received: March 12, 2013
Last Updated: July 10, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Oropharyngeal Neoplasms
Carcinoma
Carcinoma, Squamous Cell
Neoplasms, Squamous Cell
Head and Neck Neoplasms
Laryngeal Diseases
Tongue Neoplasms
Carcinoma, Verrucous
Laryngeal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Otorhinolaryngologic Diseases
Mouth Neoplasms
Mouth Diseases
Stomatognathic Diseases
Tongue Diseases
Otorhinolaryngologic Neoplasms
Respiratory Tract Neoplasms
Pharyngeal Neoplasms
Pharyngeal Diseases
Antibodies
Antibodies, Monoclonal
Docetaxel
Cetuximab
Cisplatin
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 19, 2014