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Trial record 1 of 1 for:    RTOG 3501
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TRYHARD: Radiation Therapy Plus Cisplatin With or Without Lapatinib in Treating Patients With Head and Neck Cancer. (TRYHARD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01711658
Recruitment Status : Active, not recruiting
First Posted : October 22, 2012
Last Update Posted : April 21, 2020
NRG Oncology
Information provided by (Responsible Party):
Radiation Therapy Oncology Group

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 HPV virus.

Condition or disease Intervention/treatment Phase
Non-HPV Locally Advanced Head and Neck Cancer Radiation: Intensity Modulated Radiation Therapy (IMRT) Drug: Cisplatin Drug: placebo Drug: Lapatinib Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 142 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: TRYHARD: A Phase II, Randomized, Double Blind, Placebo-Controlled Study of Lapatinib (Tykerb®) for Non-HPV Locally Advanced Head and Neck Cancer With Concurrent Chemoradiation
Actual Study Start Date : March 18, 2013
Estimated Primary Completion Date : January 1, 2021
Estimated Study Completion Date : January 1, 2026

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Placebo Comparator: Radiation therapy (IMRT) + cisplatin + placebo
Radiation therapy: Intensity Modulated Radiation Therapy (IMRT) + cisplatin + placebo
Radiation: Intensity Modulated Radiation Therapy (IMRT)
70 Gy in 2 Gy fractions

Drug: Cisplatin
100 mg/m2 on days 8 and 29

Drug: placebo
1500 mg daily one week prior to radiation, followed by 1500 mg daily concurrent with radiation, followed by 1500 mg daily for 3 months

Active Comparator: Radiation therapy (IMRT) + cisplatin + lapatinib
Radiation therapy: Intensity Modulated Radiation Therapy (IMRT) + cisplatin + lapatinib
Radiation: Intensity Modulated Radiation Therapy (IMRT)
70 Gy in 2 Gy fractions

Drug: Cisplatin
100 mg/m2 on days 8 and 29

Drug: Lapatinib
1500 mg daily one week prior to radiation, followed by 1500 mg daily concurrent with radiation, followed by 1500 mg daily for 3 months

Primary Outcome Measures :
  1. Progression-Free survival [ Time Frame: 2 years ]
    The time from randomization until local, regional, or distant disease progression, or death.

Secondary Outcome Measures :
  1. Distant metastasis [ Time Frame: 2 years ]
    The time from randomization until development of distant metastasis.

  2. Adverse Events [ Time Frame: Participants are followed for up to 8 months from the start of treatment ]
    Data is collected during protocol treatment and 30 days after whether or not related to the study drug.

  3. Compliance with planned treatment [ Time Frame: maintenance therapy is 3 months and could be different for each patient. ]
  4. Local-regional failure [ Time Frame: 2 years ]
    The time from randomization until local-regional recurrence or progression.

  5. Performance Status Scale for Head & Neck Cancer. [ Time Frame: 3 months, 1 year, and 2 years ]
  6. Functional Assessment of Cancer Therapy - Head & Neck. [ Time Frame: 3 months, 1 year, and 2 years. ]
  7. University of Michigan Xerostomia-Related Quality of Life Scale. [ Time Frame: 3 months, 1 year, and 2 years. ]
  8. HER2, EGFR, EMT as biomarkers of response. [ Time Frame: End of Study ]
  9. Overall Survival [ Time Frame: 2 years ]
    The time from randomization until death

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 N3p16 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 ENT or Head & Neck Surgeon including laryngopharyngoscopy prior to entering the study.
  • Patients must have a chest CT scan, or 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 ECHO or 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
    • AST or 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 EGFR/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 CDC definition

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01711658

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United States, Alabama
University of Alabama at Birmingham Comprehensive Cancer Center
Birmingham, Alabama, United States, 35294
United States, California
University of California, San Diego
La Jolla, California, United States, 92093
Sutter General Hospital
Sacramento, California, United States, 95816
University of California San Francisco
San Francisco, California, United States, 94143
United States, Connecticut
Yale University
New Haven, Connecticut, United States, 06520
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30308
United States, Kentucky
James Graham Brown Cancer Center at University of Louisville
Louisville, Kentucky, United States, 40202
United States, Ohio
University Hospitals of Cleveland
Cleveland, Ohio, United States, 44106
Ohio State University Medical Center
Columbus, Ohio, United States, 43210
United States, Oklahoma
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States, 73190
United States, Pennsylvania
Fox Chase Cancer Center Buckingham
Furlong, Pennsylvania, United States, 18925
United States, Texas
University of Texas Southwestern Medical School
Dallas, Texas, United States, 75390
University of Texas - MD Anderson Cancer Center
Houston, Texas, United States, 77030-4009
United States, Wisconsin
University of Wisconsin Comprehensive Cancer Center
Madison, Wisconsin, United States, 53792
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Canada, Quebec
McGill Cancer Centre at McGill University
Montreal, Quebec, Canada, H2W 1S6
Sponsors and Collaborators
Radiation Therapy Oncology Group
NRG Oncology
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Principal Investigator: Stuart Wong, MD Medical College of Wisconsin

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

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Responsible Party: Radiation Therapy Oncology Group Identifier: NCT01711658    
Other Study ID Numbers: RF-3501
LAP116153 ( Other Identifier: GlaxoSmith Kline, LLC )
First Posted: October 22, 2012    Key Record Dates
Last Update Posted: April 21, 2020
Last Verified: April 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Head and Neck Neoplasms
Neoplasms by Site
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action