TRYHARD: Radiation Therapy Plus Cisplatin With or Without Lapatinib in Treating Patients With Head and Neck Cancer.

NCT ID: NCT01711658

Last Updated: 2023-10-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 142 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-03-15
• Study Completion Date: 2022-09-21

Brief Summary

PURPOSE: This trial is studying if and how well lapatinib adds to the effectiveness of radiation therapy plus cisplatin in patients who have head and neck cancer that is not related to the human papillomavirus (HPV).

Conditions

Non-HPV Locally Advanced Head and Neck Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

IMRT + cisplatin + placebo

Intensity Modulated Radiation Therapy (IMRT) with cisplatin and placebo

Group Type: PLACEBO_COMPARATOR

IMRT

Intervention Type: RADIATION

Intensity modulated radiation therapy (IMRT), 35 fractions over 6 weeks, 6 fractions per week for 5 weeks and 5 fractions per week for 1 week, 2 Gy per fraction to total dose of 70 Gy

Cisplatin

Intervention Type: DRUG

100 mg/m\^2 administered intravenously on days 8 and 29

placebo

Intervention Type: DRUG

1500 mg placebo daily by mouth or by feeding tube starting 7 days before IMRT for 7 weeks prior to and during IMRT and 3 months after completion of IMRT

IMRT + cisplatin + lapatinib

IMRT with cisplatin and lapatinib

Group Type: ACTIVE_COMPARATOR

IMRT

Intervention Type: RADIATION

Intensity modulated radiation therapy (IMRT), 35 fractions over 6 weeks, 6 fractions per week for 5 weeks and 5 fractions per week for 1 week, 2 Gy per fraction to total dose of 70 Gy

Cisplatin

Intervention Type: DRUG

100 mg/m\^2 administered intravenously on days 8 and 29

Lapatinib

Intervention Type: DRUG

1500 mg lapatinib by mouth or by feeding tube daily starting 7 days before IMRT for 7 weeks prior to and during IMRT and 3 months after completion of IMRT

Interventions

IMRT

Intensity modulated radiation therapy (IMRT), 35 fractions over 6 weeks, 6 fractions per week for 5 weeks and 5 fractions per week for 1 week, 2 Gy per fraction to total dose of 70 Gy

Intervention Type: RADIATION

Cisplatin

100 mg/m\^2 administered intravenously on days 8 and 29

Intervention Type: DRUG

placebo

1500 mg placebo daily by mouth or by feeding tube starting 7 days before IMRT for 7 weeks prior to and during IMRT and 3 months after completion of IMRT

Intervention Type: DRUG

Lapatinib

1500 mg lapatinib by mouth or by feeding tube daily starting 7 days before IMRT for 7 weeks prior to and during IMRT and 3 months after completion of IMRT

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients must have histologically or cytologically confirmed diagnosis (from primary lesion and/or lymph nodes) of Squamous Cell Cancer of the oropharynx, hypopharynx or larynx (For patients with oropharynx primary, the tumor must be negative for p16 by immunohistochemistry).
• Patients with selected Stage III or IV disease (T2 N2-3 M0, T3-4 any N M0, T1 N2b, N2c or N3 p16 negative oropharynx cancer or T1-2 any N+ hypopharynx cancer) including no distant metastases.
• History/Physical examination by a Radiation Oncologist and Medical oncologist prior to entering the study.
• Examination by an ears, nose, throat (ENT) or Head & Neck Surgeon including laryngopharyngoscopy prior to entering the study.
• Patients must have a chest CT scan, or positron emission tomography (PET)/CT scan to rule out metastatic disease
• Patients must have a contrast enhanced CT scan or MRI or PET/CT scan of the tumor site and neck nodes prior to entering the study.
• Patients must have an EKG and echocardiogram (ECHO) or multigated acquisition (MUGA) scan prior to entering the study.
• Patients must have Zubrod Performance Status of 0-1.
• Patients must be ≥ 18 years of age.
• Patients must have normal organ and marrow function as defined below:

• Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3
• Platelets ≥ 100,000 cells/mm3
• Hemoglobin ≥ 8.0 g/dl
• Serum creatinine < 1.5 mg/dl or creatinine clearance (CC) ≥ 50 ml/min
• Total bilirubin < 2 x the institutional upper limit of normal
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 3 x the institutional upper limit of normal
• Patient must have magnesium, calcium, glucose, potassium and sodium levels within normal limits
• Women of childbearing potential must have a negative pregnancy test prior to registration.
• Patients of reproductive potential must practice effective contraception while on study and for at least 60 calendar days following treatment.
• All patients must sign an informed consent prior to enrollment.
• Patients must comply with the treatment plan and follow-up schedule.

Exclusion Criteria

• Patients with simultaneous primaries or bilateral tumors.
• Patients who have had gross total excision of the primary tumor.
• Patients with initial surgical treatment, radical or modified neck dissection.
• Patients who received prior systemic chemotherapy for the study cancer.
• Patients who received prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields.
• Patients with primary tumor of oral cavity, nasopharynx, sinuses or salivary glands.
• Prior allergic reaction to the study drugs.
• Patients who have had prior therapy that specifically and directly targets the epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor 2 (HER2) pathway.
• Patients who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, or stable chronic liver disease per investigator assessment);
• Pregnant women or sexually active patients not willing or able to use medically acceptable forms of contraceptive method while on treatment.
• Patients with severe, active co-morbidity, defined as follows:

• Uncontrolled cardiac disease, such as uncontrolled hypertension, unstable angina, and/or congestive heart failure requiring hospitalization within the last 6 months
• Transmural myocardial infarction within the last 6 months
• Left ventricular ejection fraction < 45%
• 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 within 30 calendar days prior to registration
• Hepatic insufficiency resulting in clinical jaundice and/or Coagulation defects
• Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

Novartis

INDUSTRY

Sponsor Role: collaborator

Radiation Therapy Oncology Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stuart Wong, MD

Role: PRINCIPAL_INVESTIGATOR

Medical College of Wisconsin

Locations

University of Alabama at Birmingham Comprehensive Cancer Center

Birmingham, Alabama, United States

University of California, San Diego

La Jolla, California, United States

Sutter General Hospital

Sacramento, California, United States

University of California San Francisco

San Francisco, California, United States

Yale University

New Haven, Connecticut, United States

Emory University

Atlanta, Georgia, United States

James Graham Brown Cancer Center at University of Louisville

Louisville, Kentucky, United States

University Hospitals of Cleveland

Cleveland, Ohio, United States

Ohio State University Medical Center

Columbus, Ohio, United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Fox Chase Cancer Center Buckingham

Furlong, Pennsylvania, United States

University of Texas Southwestern Medical School

Dallas, Texas, United States

University of Texas - MD Anderson Cancer Center

Houston, Texas, United States

University of Wisconsin Comprehensive Cancer Center

Madison, Wisconsin, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

McGill Cancer Centre at McGill University

Montreal, Quebec, Canada

Countries

United States; Canada

References

Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tan PF, Westra WH, Chung CH, Jordan RC, Lu C, Kim H, Axelrod R, Silverman CC, Redmond KP, Gillison ML. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010 Jul 1;363(1):24-35. doi: 10.1056/NEJMoa0912217. Epub 2010 Jun 7.

Reference Type: BACKGROUND

PMID: 20530316 (View on PubMed)

Harrington K. et al. Phase II study of oral Lapatinib, a dual-tyrosine kinase inhibitor, combined with chemoradiotherapy (CRT) in patients with advanced squamous cell carcinoma of the head and neck (SCCHN). J Clin Oncol. 28:15s, 2010 suppl. Abstract 5505. GSK study 884

Reference Type: BACKGROUND

Wong SJ, Torres-Saavedra PA, Saba NF, Shenouda G, Bumpous JM, Wallace RE, Chung CH, El-Naggar AK, Gwede CK, Burtness B, Tennant PA, Dunlap NE, Redman R, Stokes WA, Rudra S, Mell LK, Sacco AG, Spencer SA, Nabell L, Yao M, Cury FL, Mitchell DL, Jones CU, Firat S, Contessa JN, Galloway T, Currey A, Harris J, Curran WJ Jr, Le QT. Radiotherapy Plus Cisplatin With or Without Lapatinib for Non-Human Papillomavirus Head and Neck Carcinoma: A Phase 2 Randomized Clinical Trial. JAMA Oncol. 2023 Nov 1;9(11):1565-1573. doi: 10.1001/jamaoncol.2023.3809.

Reference Type: DERIVED

PMID: 37768670 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

LAP116153

Identifier Type: OTHER

Identifier Source: secondary_id

RF-3501

Identifier Type: -

Identifier Source: org_study_id