NCT00265941|CompletedPhase 3ResultsDMC

Radiation Therapy and Cisplatin With or Without Cetuximab in Treating Patients With Stage III or Stage IV Head and Neck Cancer

A Randomized Phase III Trial of Concurrent Accelerated Radiation and Cisplatin Versus Concurrent Accelerated Radiation, Cisplatin, and Cetuximab (C225) [Followed by Surgery for Selected Patients] for Stage III and IV Head and Neck Carcinomas

Radiation Therapy Oncology Group ClinicalTrials.gov

Compare

3 other identifiers

RTOG 0522CDR0000458049NCI-2009-00729

Study Type

interventional

Target

940

Locations

2 countries

Sites

372

Timeline

RegisteredDec 2005

StartedNov 2005

CompletionMay 2022

Brief Summary

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Cisplatin may also make tumor cells more sensitive to radiation therapy. 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. Giving radiation therapy and cisplatin together with cetuximab may kill more tumor cells. It is not yet known whether radiation therapy and cisplatin are more effective with or without cetuximab in treating head and neck cancer. PURPOSE: This randomized phase III trial is studying radiation therapy, cisplatin, and cetuximab to see how well they work compared to radiation therapy and cisplatin in treating patients with stage III or stage IV head and neck cancer.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

940

participants targeted

Target at P75+ for phase_3 head-and-neck-cancer

Timeline

Completed

Started Nov 2005

Longer than P75 for phase_3 head-and-neck-cancer

Geographic Reach

2 countries

372 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

16.6 years study duration

Study Start

First participant enrolled

November 1, 2005

Completed

1 month until next milestone

First Submitted

Initial submission to the registry

December 14, 2005

Completed

1 day until next milestone

First Posted

Study publicly available on registry

December 15, 2005

Completed

5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2011

Completed

7 years until next milestone

Results Posted

Study results publicly available

December 21, 2017

Completed

4.4 years until next milestone

Study Completion

Last participant's last visit for all outcomes

May 20, 2022

Completed

Last Updated

June 14, 2022

Status Verified

May 1, 2022

Enrollment Period

5.2 years

First QC Date

December 14, 2005

Results QC Date

September 26, 2017

Last Update Submit

May 23, 2022

Conditions

Head and Neck Cancer

Keywords

stage III squamous cell carcinoma of the hypopharynxstage IV squamous cell carcinoma of the hypopharynxstage III squamous cell carcinoma of the larynxstage IV squamous cell carcinoma of the larynxstage III squamous cell carcinoma of the oropharynxstage IV squamous cell carcinoma of the oropharynx

Outcome Measures

Primary Outcomes (1)

Progression-free Survival (PFS) (3-year Rate Reported)
Progression-free survival (PFS) is defined as time from randomization to date of local, regional, or distant disease progression, or death from any cause. Patients last known to be alive without progression are censored at the date of last contact. Three-year rates were estimated by the Kaplan-Meier method. Local or regional progression is defined as an estimated increase in the size of the tumor (product of the perpendicular diameters of the two largest dimensions) of greater than 25%, taking as reference the smallest value of all previous measurements or appearance of new areas of malignant disease. Distant progression is defined as clear evidence of distant metastases.
From randomization until 434 failures have occurred, approximately 5 years from start of study. (Patients are followed until death or study termination, whichever occurs first.)

Secondary Outcomes (12)

Overall Survival (OS) (3-year Rate Reported)
From randomization until 434 failures have occurred, approximately 5 years from start of study. (Patients are followed until death or study termination, whichever occurs first.)
Local-regional Failure (LRF) (3-year Rate Reported)
From randomization until 434 failures have occurred, approximately 5 years from start of study. (Patients are followed until death or study termination, whichever occurs first.)
Rate of Mucositis Toxicity ≥ Grade 3
From start of treatment until 434 failures have occurred, approximately 5 years from start of study. (Patients are followed until death or study termination, whichever occurs first.)
Rate of Other Toxicity ≥ Grade 3 (Not Mucositis)
From start of treatment until 434 failures have occurred, approximately 5 years from start of study. (Patients are followed until death or study termination, whichever occurs first.)
Rate of Patients Who Tolerated Treatment
From start of treatment to end of treatment (6-7 weeks)
+7 more secondary outcomes

Study Arms (2)

RT + cisplatin

ACTIVE COMPARATOR

Radiation therapy (RT) as accelerated fractionation by concomitant boost (AFX-CB) or intensity-modulated radiation therapy (IMRT) plus cisplatin

Drug: cisplatinRadiation: Accelerated Fractionation by Concomitant BoostRadiation: Intensity-modulated radiation therapy

RT + cisplatin + cetuximab

EXPERIMENTAL

Radiation therapy (RT) as accelerated fractionation by concomitant boost (AFX-CB) or intensity-modulated radiation therapy (IMRT) plus cisplatin plus cetuximab

Drug: cetuximabDrug: cisplatinRadiation: Accelerated Fractionation by Concomitant BoostRadiation: Intensity-modulated radiation therapy

Interventions

cetuximabDRUG

Cetuximab 400 mg/m\^2 IV loading dose 5-7 days before start of radiation therapy, then 250 mg/m\^2 IV weekly for 7 weeks

RT + cisplatin + cetuximab

cisplatinDRUG

Cisplatin 100 mg/m\^2 IV on days 1 and 22

RT + cisplatinRT + cisplatin + cetuximab

Accelerated Fractionation by Concomitant BoostRADIATION

3DCRT 54 Gy in 30 1.8 Gy fractions over 6 weeks with boost 18 Gy in 12 1.5 Gy fractions for last 12 days, for a total of 72 Gy in 42 fractions over 6 weeks

Also known as: AFX-CB

RT + cisplatinRT + cisplatin + cetuximab

Intensity-modulated radiation therapyRADIATION

70 Gy in 35 2.0 Gy fractions over 6 weeks with 6 fractions per week (on Saturday or as second daily fraction) in 5 of the 6 weeks.

Also known as: IMRT

RT + cisplatinRT + cisplatin + cetuximab

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

Pathologically (histologically or cytologically) proven (from primary lesion and/or lymph nodes) diagnosis of squamous cell carcinoma of the oropharynx, hypopharynx, or larynx;
Selected stage III or IV disease (T2N2-3M0, T3-4 any N M0); Note: Patients with T1, any N, or T2N1 tumors are not eligible.
Appropriate stage for protocol entry, including no distant metastases, based upon the following minimum diagnostic workup:
History/physical examination within 4 weeks prior to registration, including assessment of weight and weight loss in past 6 months and an examination by a Medical Oncologist;
Chest x-ray (or Chest CT scan or PET/CT scan) within 6 weeks prior to registration;
CT scan or MRI of the head and neck (of the primary tumor and neck nodes) or PET/CT scan within 6 weeks prior to registration; see Section 6.11 for details of PET scans. Note: A PET/CT can only be used instead of a CT scan or MRI if the CT is a high quality scan with contrast.
Left ejection fraction determined by echocardiogram and/or multiple gated acquisition (MUGA) technique within 12 weeks of registration;
Zubrod Performance Status 0-1;
Age \> 18;
Adequate bone marrow function, defined as follows:
Absolute neutrophil count (ANC) \> 1,800 cells/mm3 based upon CBC/differential obtained within 2 weeks prior to registration on study;
Platelets \> 100,000 cells/mm3 based upon complete blood count (CBC)/differential obtained within 2 weeks prior to registration on study;
Hemoglobin \> 8.0 g/dl based upon CBC/differential obtained within 2 weeks prior to registration on study (Note: The use of transfusion or other intervention to achieve Hgb \> 8.0 g/dl is acceptable.)
Adequate hepatic function, defined as follows:
Bilirubin \< 1.5 mg/dl within 2 weeks prior to registration on study; For patients with Gilbert's disease as the sole cause of elevated bilirubin, please contact the PI, Dr. Ang.
+7 more criteria

You may not qualify if:

Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years;
Patients with simultaneous primaries or bilateral tumors are excluded.
Gross total excision (e.g., by tonsillectomy) of the primary tumor; however, partial removal of the tumor to alleviate an impending airway obstruction does not make the patient ineligible.
Prior systemic chemotherapy 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;
Primary site of tumor of oral cavity, nasopharynx, sinuses, or salivary glands;
Initial surgical treatment, excluding diagnostic biopsy of the primary site or nodal sampling of neck disease; radical or modified neck dissection is not permitted.
Severe, active co-morbidity, defined as follows:
Current uncontrolled cardiac disease; i.e., uncontrolled hypertension, unstable angina, recent myocardial infarction (within prior 6 months), uncontrolled congestive heart failure, and cardiomyopathy with decreased ejection fraction;
Left Ventricular Ejection Fraction \< 45%;
Transmural myocardial infarction within the last 6 months;
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;
Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that 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.
Any uncontrolled condition, which in the opinion of the investigator, would interfere in the safe and timely completion of study procedures;
+9 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Radiation Therapy Oncology Grouplead
National Cancer Institute (NCI)collaborator
NRG Oncologycollaborator

Study Sites (372)

Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham

Birmingham, Alabama, 35294, United States

Location

Providence Cancer Center

Anchorage, Alaska, 99508, United States

Location

Mayo Clinic Scottsdale

Scottsdale, Arizona, 85259-5499, United States

Location

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

Auburn Radiation Oncology

Auburn, California, 95603, United States

Location

Alta Bates Summit Comprehensive Cancer Center

Berkeley, California, 94704, United States

Location

Peninsula Medical Center

Burlingame, California, 94010, United States

Location

Radiation Oncology Centers - Cameron Park

Cameron Park, California, 95682, United States

Location

Mercy Cancer Center at Mercy San Juan Medical Center

Carmichael, California, 95608, United States

Location

East Bay Radiation Oncology Center

Castro Valley, California, 94546, United States

Location

Valley Medical Oncology Consultants - Castro Valley

Castro Valley, California, 94546, United States

Location

Cancer Care Center at John Muir Health - Concord Campus

Concord, California, 94524-4110, United States

Location

City of Hope Comprehensive Cancer Center

Duarte, California, 91010-3000, United States

Location

Valley Medical Oncology

Fremont, California, 94538, United States

Location

Virginia K. Crosson Cancer Center at St. Jude Medical Center

Fullerton, California, 92835, United States

Location

Marin Cancer Institute at Marin General Hospital

Greenbrae, California, 94904, United States

Location

Sutter Health - Western Division Cancer Research Group

Greenbrae, California, 94904, United States

Location

Rebecca and John Moores UCSD Cancer Center

La Jolla, California, 92093-0658, United States

Location

USC/Norris Comprehensive Cancer Center and Hospital

Los Angeles, California, 90089-9181, United States

Location

Memorial Medical Center

Modesto, California, 95355, United States

Location

Alta Bates Summit Medical Center - Summit Campus