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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.
 
ClinicalTrials.gov Identifier: NCT01711658
Recruitment Status : Active, not recruiting
First Posted : October 22, 2012
Results First Posted : November 29, 2021
Last Update Posted : November 29, 2021
Sponsor:
Collaborators:
GlaxoSmithKline
Novartis
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 human papillomavirus (HPV).

Condition or disease Intervention/treatment Phase
Non-HPV Locally Advanced Head and Neck Cancer Radiation: 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 15, 2013
Actual Primary Completion Date : December 1, 2020
Estimated Study Completion Date : January 1, 2026

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: IMRT + cisplatin + placebo
Intensity Modulated Radiation Therapy (IMRT) with cisplatin and placebo
Radiation: 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

Drug: Cisplatin
100 mg/m^2 administered intravenously on days 8 and 29

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

Active Comparator: IMRT + cisplatin + lapatinib
IMRT with cisplatin and lapatinib
Radiation: 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

Drug: Cisplatin
100 mg/m^2 administered intravenously on days 8 and 29

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




Primary Outcome Measures :
  1. Percentage of Participants Alive Without Progression (Progression-free Survival) [ Time Frame: From randomization to last follow-up. Maximum follow-up at time of analysis was 7.1 years. ]
    An event for progression-free survival is local, regional, or distant disease progression or death due to any cause. Progression-free survival time is defined as time from randomization to the date of progression/death or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. The protocol specifies that the distributions of survival times be compared between the arms, which is reported in the statistical analysis results. Five-year rates are provided. Analysis occurred after 67 progressions or deaths were reported.


Secondary Outcome Measures :
  1. Percentage of Participants Alive (Overall Survival) [ Time Frame: From randomization to last follow-up. Maximum follow-up at time of analysis was 7.1 years. ]
    An event for overall survival is death due to any cause. Overall survival time is defined as time from randomization to the date of death or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. The protocol specifies that the distributions of survival times be compared between the arms, which is reported in the statistical analysis results. Five-year rates are provided.

  2. Percentage of Participants With Distant Metastases [ Time Frame: From randomization to last follow-up. Maximum follow-up at time of analysis was 7.1 years. ]
    Failure for distant metastasis endpoint was defined as distant progression; local-regional failure and death due to any cause were considered competing risks. Distant metastasis time is defined as time from randomization to the date of progression/death or last known follow-up (censored). Rates are estimated by the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Five-year rates are provided.

  3. Percentage of Participants With Treatment-related Grade 3 or Higher Adverse Events [ Time Frame: From start of treatment to last follow-up. Maximum follow-up at time of analysis was 7.1 years. ]
    Adverse events (AE) were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grade refers to the severity of the AE. The CTCAE v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to adverse event. "Treatment-related" is defined definitely, probably, or possibly related to treatment.

  4. Percentage of Participants Who Complied With Protocol Treatment [ Time Frame: From start of treatment to end of treatment (approximately 5 months from randomization). ]
    Compliance with protocol treatment is defined as "per protocol" or "acceptable variation" per study chair review for IMRT, cisplatin, pre-IMRT lapatinib/placebo, concurrent lapatinib/placebo, and maintenance lapatinib/placebo. Rates of treatment compliance were compared between groups by a 2-sided Fisher's exact test.

  5. Percentage of Participants With Local-regional Progression [ Time Frame: From randomization to last follow-up. Maximum follow-up at time of analysis was 7.1 years. ]
    Failure for local-regional control endpoint was defined as local or regional progression, salvage surgery of the primary tumor with tumor present/unknown, salvage neck dissection with tumor present/unknown > 20 weeks after the end of radiation therapy, death due to study cancer without documented progression, or death due to unknown causes without documented progression; distant metastasis and death due to other causes were considered competing risks. Local-regional failure time is defined as time from randomization to the date of progression/death or last known follow-up (censored). Failure rates are estimated by the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Five-year rates are provided.

  6. Performance Status Scale for Head & Neck Cancer. [ Time Frame: 3 months, 1 year, and 2 years ]
  7. Functional Assessment of Cancer Therapy - Head & Neck. [ Time Frame: 3 months, 1 year, and 2 years. ]
  8. University of Michigan Xerostomia-Related Quality of Life Scale. [ Time Frame: 3 months, 1 year, and 2 years. ]
  9. HER2, EGFR, EMT as Biomarkers of Response. [ Time Frame: End of Study ]


Information from the National Library of Medicine

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

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 ClinicalTrials.gov identifier (NCT number): NCT01711658


Locations
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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
GlaxoSmithKline
Novartis
Investigators
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Principal Investigator: Stuart Wong, MD Medical College of Wisconsin
  Study Documents (Full-Text)

Documents provided by Radiation Therapy Oncology Group:
Informed Consent Form  [PDF] September 27, 2016

Publications:
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
ClinicalTrials.gov Identifier: NCT01711658    
Other Study ID Numbers: RF-3501
LAP116153 ( Other Identifier: GlaxoSmith Kline, LLC )
First Posted: October 22, 2012    Key Record Dates
Results First Posted: November 29, 2021
Last Update Posted: November 29, 2021
Last Verified: October 2021

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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
Neoplasms
Cisplatin
Lapatinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action