Clinical Trial ECOGTHNR0920
A Phase III Study of Postoperative Radiation Therapy (IMRT) +/- Cetuximab for Locally-Advanced Resected Head and Neck Cancer
- Protocol No. ECOGTHNR0920
- Open Date: 09/12/2012
- Staging: Phase III
- Age Group: Adults
- Scope: International
- Objective: Test whether the addition of cetuximab to radiation therapy will improve overall survival (OS) in postoperative patients with intermediate risk following surgery
- Disease Sites: Head/Neck
- Therapies: Molecular Targeted Agents / Immunotherapy / Biologics; Radiotherapy
- Drugs: Cetuximab; Cetuximab (Erbitux)
- Participating Institutions: Vanderbilt University
- National Clinical Trial ID: NCT01311063
- Secondary Protocol No: RTOG 0920
Participants are being asked to take part in this research study because they have head and neck cancer that after surgery has an intermediate risk of recurring. The standard treatment of surgery (which they have had) followed by radiation therapy can stop tumors from growing in the head and neck region in most patients. However, the cancer can recur or can spread to other parts of the body. Cetuximab is a drug that may delay or prevent tumor growth by blocking certain cellular chemical pathways that lead to tumor development. It was approved by the FDA in 2006 for the treatment of head and neck cancer. The purpose of this study is to compare the effects, good and/or bad, of radiation therapy alone with radiation therapy and cetuximab on participants and their cancer to find out which is better. In this study, they will get either radiation therapy alone OR radiation therapy and cetuximab. If they participate in this study, participants will receive intensity modulated radiation therapy (IMRT). IMRT is a form of radiation in which radiation beams are designed to avoid important normal parts of their body, such as the salivary glands. Study doctors also may decide to use a technique called image guided radiation therapy (IGRT). The purpose of IGRT is to give radiation treatment more accurately to tumors while decreasing the radiation to normal tissues. Small adjustments in the radiation treatment are made each treatment day based on x-ray images taken right before each day's treatment to ensure that radiation treatments are given as accurately as possible. Use of IGRT may lead to improved accuracy of radiation treatment compared to regular radiation therapy and eventually, that will be more useful against cancer. At this time, however, there is no proof that using this technique is more useful against cancer than regular radiation treatment without this technique. This study is being conducted by the Radiation Therapy Oncology Group (RTOG). RTOG is a group of researchers at different sites that conduct research for the National Cancer Institute (NCI). Study doctors are members of RTOG or another group participating in the study. About 700 people will take part in this study across all sites. About 8 people will take part at Vanderbilt.
|Ages Eligible for Study:||18 Years to 90 Years|
|Genders Eligible for Study:||Both|
|Accepts Healthy Volunteers:||No|
• 3.1 Conditions for Patient Eligibility 3.1.1 Pathologically (histologically) proven diagnosis of squamous cell carcinoma (including variants such as verrucous carcinoma, spindle cell carcinoma, carcinoma NOS, etc.) of the head/neck (oral cavity, oropharynx or larynx); Note: Hypopharynx primaries are excluded because these patients have both a poor prognosis and high likelihood of post-radiation complications.
3.1.2 Clinical stage T1, N1-2 or T2-3, N0-2, M0 including no distant metastases, based upon the following minimum diagnostic workup: 18.104.22.168 General history and physical examination by a Radiation Oncologist and/or Medical Oncologist within 8 weeks prior to registration; 22.214.171.124 Examination by an ENT or Head & Neck Surgeon, including laryngopharyngoscopy (mirror and/or fiberoptic and/or direct procedure), within 8 weeks prior to registration; 126.96.36.199 Chest x-ray (at a minimum) or chest CT scan (with or without contrast) or CT/PET of chest (with or without contrast) within 8 weeks prior to registration. 3.1.3 Gross total resection of the primary tumor with curative intent must be completed within 7 weeks of registration with surgical pathology demonstrating one or more of the following "intermediate" risk factors: 188.8.131.52 Perineural invasion; 184.108.40.206 Lymphovascular invasion; 220.127.116.11 Single lymph node > 3 cm or ≥ 2 lymph nodes (all < 6 cm) [no extracapsular extension]; 18.104.22.168 Close margin(s) of resection, defined as cancer extending to within 5 mm of a surgical margin; 22.214.171.124 T3 or microscopic T4a primary tumor (Note: Gross T4a or T4b is ineligible); 126.96.36.199 T2 oral cavity cancer with > 5 mm depth of invasion. 3.1.4 Zubrod Performance Status of 0-1 within 2 weeks prior to registration; 3.1.5 Age ≥ 18; 3.1.6 CBC/differential obtained within 4 weeks prior to registration on study, with adequate bone marrow function defined as follows: 188.8.131.52 Absolute granulocyte count (AGC) ≥ 1,500 cells/mm3; 184.108.40.206 Platelets ≥ 100,000 cells/mm3; RTOG 0920 18 220.127.116.11 Hemoglobin ≥ 8.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is acceptable). 3.1.7 Adequate hepatic function, defined as follows: 18.104.22.168 Total bilirubin < 2 x institutional ULN within 2 weeks prior to registration; 22.214.171.124 AST or ALT < 3 x institutional ULN within 2 weeks prior to registration.
3.1.8 Adequate renal function, defined as follows: 126.96.36.199 Serum creatinine < 2 x institutional ULN within 2 weeks prior to registration or; creatinine clearance (CC) ≥ 50 ml/min within 2 weeks prior to registration determined by 24- hour collection or estimated by Cockcroft-Gault formula: CCr male = [(140•age) x (wt in kg)] [(Serum Cr mg/dl) x (72)] CCr female = 0.85 x (CrCl male) 3.1.9 Negative serum pregnancy test within 2 weeks prior to registration for women of childbearing potential; 3.1.10 (6/4/10) The following assessments are required within 2 weeks prior to the start of registration: Na, K, Cl, glucose, Ca, 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 (e.g., magnesium oxide) at the investigator's discretion. 3.1.11 Women of childbearing potential and male participants who are sexually active must agree to use a medically effective means of birth control; 3.1.12 Patients must provide study specific informed consent prior to study entry, including consent for mandatory tissue submission for EGFR and for oropharyngeal patients, HPV analyses.
• 3.2.1 Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 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. 3.2.2 Per the operative report, positive margin(s) [defined as tumor present at the cut or inked edge of the tumor], nodal extracapsular extension, and/or gross residual disease after surgery; 3.2.3 Prior systemic chemotherapy or anti-EGF therapy for the study cancer; note: prior chemotherapy or anti-EGF therapy for a different cancer is allowable. See section 3.2.1.
3.2.4 Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields; 3.2.5 Severe, active co-morbidity, defined as follows: 188.8.131.52 Unstable angina and/or congestive heart failure requiring hospitalization within 6 months prior to registration; 184.108.40.206 Transmural myocardial infarction within 6 months prior to registration; 220.127.116.11 Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration; 18.104.22.168 Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration; 22.214.171.124 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; 126.96.36.199 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.
188.8.131.52 Acquired Immune Deficiency Syndrome (AIDS) based upon current 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. 184.108.40.206 (6/4/10) Grade 3-4 electrolyte abnormalities (CTCAE, v. 4.0):