Clinical trial NCT01893307: Intensity-Modulated Proton Beam Therapy or Intensity-Modulated Photon Therapy in Treating Patients With Stage III-IVB Oropharyngeal Cancer
Official title: Phase III Randomized Trial of Intensity-Modulated Proton Beam Therapy (IMPT) Versus Intensity-Modulated Photon Therapy (IMRT) for the Treatment of Oropharyngeal Cancer of the Head and Neck
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7
Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7
Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: National Institute of Dental and Craniofacial Research (NIDCR)
First posted: 2013-07-09
Enrollment: 440
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This randomized phase III trial studies the side effects and how well intensity-modulated proton beam therapy works and compares it to intensity-modulated photon therapy in treating patients with stage III-IVB oropharyngeal cancer. Radiation therapy uses high-energy x-rays, protons, and other types of radiation to kill tumor cells and shrink tumors. It is not yet known whether intensity-modulated proton beam therapy is more effective than intensity-modulated photon therapy in treating oropharyngeal cancer.

Detailed description: PRIMARY OBJECTIVES:

To compare the progression-free survival (PFS) between concurrent chemo-radiation strategies with IMRT and IMPT following the treatment of oropharyngeal tumors.

SECONDARY OBJECTIVES:

1. To assess and compare overall survival between IMRT and IMPT along with estimating disease-related outcomes such as: \[2-year progression-free survival, patterns of failure, 2-year overall survival, 2-year distant metastasis free survival, and second primary cancers\]
2. To assess acute and chronic/late side effects, and to compare the rates of Grade 3-5 toxicity between IMRT and IMPT following the treatment of oropharyngeal tumors.
3. To assess Patient Reported Outcome (PRO) measures of symptoms using MD Anderson Symptom Inventory (MDASI), MD Anderson Dysphagia Inventory (MDADI), FACT-HN, Xerostomia and Health Questionnaire (EQ-5D-3L), Work status (WPAI: SHP)
4. To assess Physician Reported Toxicity using Common Terminology Criteria for Adverse Events (CTCAE)-4.0
5. To evaluate and compare Quality-Adjusted-Life-Years (QALY) between IMPT and IMRT;
6. To perform Cost-benefit economic analysis of treatment;
7. To determine whether specific molecular profiles are associated with overall or progression-free survival;
8. To investigate associations between changes in blood biomarkers, or HPV-specific cellular immune responses, or HPV ctDNA (measured at baseline and three months and at each follow-up visit for up to 10 years) with overall or progression-free survival;
9. To bank peripheral blood at time of enrollment, weeks 2, 4, and 6 during treatment and at each follow up visits for up to 10 years to explore the ability of circulating markers to predict outcome;
10. To bank head and neck tissues to explore the ability of tissue-based markers to predict outcome;
11. To bank peripheral blood and tissues for future interrogations; Finally, all additional secondary endpoints

EXPLORATORY OBJECTIVE:

I. To assess potential differences between patients on study and patients who were considered eligible for randomized, were randomized to a treatment arm, but were denied insurance coverage for the treatment arm she/he was randomized to; or may have dropped out of the study for other reasons after being randomized. These patients will compromise Group 3: consisting of patients randomized to Protons but not treated and Group 4: consisting of patients randomized to IMRT but not treated at the designated institution. Furthermore, these patients will only be followed for recurrence and survival.(Phase III)

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients undergo IMRT once daily (QD) five days a week for approximately 6.5 weeks.

ARM II: Patients undergo IMPT QD five days a week for approximately 6.5 weeks.

After completion of study treatment, patients are followed up every 3 months for 1 year, every 4 months for 1 year, and then every 6 months for 5 years.

Eligibility criteria: Inclusion Criteria:

* Histologically documented squamous cell carcinoma of the oropharynx (American Joint Committee on Cancer \[AJCC\] version \[v\]7 stage III-IV A,B)
* Tumor tissue (primary or cervical metastasis) available for human papilloma virus (HPV) and/or p16 (in situ hybridization \[ISH\], immunohistochemistry \[IHC\] or genotyping testing); if you do not have enough leftover tumor tissue available, you will have a tumor biopsy for tumor marker testing
* Eastern Cooperative Oncology Group (ECOG) performance status = 0, 1, or 2
* Negative pregnancy test for women of child bearing potential
* Concurrent chemotherapy
* Bilateral neck radiation

Exclusion Criteria:

* Previous radiation treatment for head and neck mucosal primary cancers within the past 5 years (i.e. oropharynx, nasopharynx, hypopharynx, larynx, and oral cavity)
* Pregnant or breast-feeding females
* Clinically significant uncontrolled major cardiac, respiratory, renal, hepatic, gastrointestinal or hematologic disease but not limited to:

  * Symptomatic congestive heart failure, unstable angina, or cardiac dysrhythmia not controlled by pacer device
  * Myocardial infarction within 3 months of registration
* Distant metastases (stage IV C, any T, any N and M1)
* Previous surgical resection or neck dissection for oropharyngeal cancer, administered with therapeutic intent

Primary outcomes:
measure: Cumulative incidence of late onset grade 3+ toxicity anytime (Phase II)
timeFrame: Up to 2 years
measure: Cumulative incidence of acute grade 3+ toxicity (Phase II)
timeFrame: Up to 2 years
measure: Overall survival (OS) (Phase II)
timeFrame: Up to 5 years
measure: Overall survival (Phase III)
timeFrame: Up to 5 years
measure: Progression-free survival (Phase III)
timeFrame: Up to 3 years
Secondary outcomes:
measure: Quality of life (QoL) (Phase II and III)
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Scottsdale
country: United States
facility: Mayo Clinic in Arizona
state: Arizona
city: Gainesville
country: United States
facility: University of Florida Health Science Center - Gainesville
state: Florida
city: Miami
country: United States
facility: Miami Cancer Institute
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital/Winship Cancer Institute
state: Georgia
city: Warrenville
country: United States
facility: Northwestern Medicine Cancer Center Warrenville
state: Illinois
city: Shreveport
country: United States
facility: Willis-Knighton Medical and Cancer Center
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland/Greenebaum Cancer Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Detroit
country: United States
facility: Wayne State University/Karmanos Cancer Institute
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
city: New York
country: United States
facility: New York Proton Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Philadelphia
country: United States
facility: University of Pennsylvania/Abramson Cancer Center
state: Pennsylvania
city: Conroe
country: United States
facility: MD Anderson in The Woodlands
state: Texas
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
city: Houston
country: United States
facility: MD Anderson West Houston
state: Texas
city: League City
country: United States
facility: MD Anderson League City
state: Texas
city: Sugar Land
country: United States
facility: MD Anderson in Sugar Land
state: Texas
city: Fairfax
country: United States
facility: Inova Schar Cancer Institute
state: Virginia
city: Seattle
country: United States
facility: Fred Hutch/University of Washington Cancer Consortium
state: Washington
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Steven J Frank
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gunn GB, Blanchard P, Garden AS, Zhu XR, Fuller CD, Mohamed AS, Morrison WH, Phan J, Beadle BM, Skinner HD, Sturgis EM, Kies MS, Hutcheson KA, Rosenthal DI, Mohan R, Gillin MT, Frank SJ. Clinical Outcomes and Patterns of Disease Recurrence After Intensity Modulated Proton Therapy for Oropharyngeal Squamous Carcinoma. Int J Radiat Oncol Biol Phys. 2016 May 1;95(1):360-367. doi: 10.1016/j.ijrobp.2016.02.021. Epub 2016 Feb 12.