Neoplasms

All Conditions

Head and Neck Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Cisplatin

Lapatinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Intensity Modulated Radiation Therapy (IMRT) with cisplatin and placebo

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

IMRT

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

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

placebo

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

Stuart Wong, MD

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).

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

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

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.

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.

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.

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.

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.

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.

GlaxoSmithKline

Novartis

Radiation Therapy Oncology Group

All-cause mortality was assessed in all randomized participants. Adverse events were assessed in participants who started protocol treatment

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

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

IMRT + Cisplatin + Placebo

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

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

IMRT + Cisplatin + Lapatinib

Total

Age, Continuous

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

0 = Asymptomatic; 1 = Symptomatic but completely ambulatory; 2 = Symptomatic, \<50% in bed during the day; 3 = Symptomatic, \>50% in bed, but not bedbound; 4 = Bedbound; 5 = Death

Zubrod performance status

Smoking history as measured in pack-years. It is calculated by multiplying the number of packs of cigarettes smoked per day by the number of years the person has smoked.

Two patients are missing smoking history data.

Smoking history: pack-years

Primary site

Tumor stage per the American Joint Committee on Cancer (AJCC) 7th ed. refers to the size and/or extent of the main tumor. The higher the number after the T, the larger the tumor or the more it has grown into nearby tissues.

T stage (stratification factor)

Regional lymph nodes staging per American Joint Committee on Cancer (AJCC) 7th ed. refers to the number and/or extent of spread of lymph nodes that contain cancer. N0 means lymph nodes aren't involved. A higher number means the cancer is in more lymph nodes, farther away from the original tumor.

N stage (stratification factor)

Overall cancer stage per American Joint Committee on Cancer (AJCC) 7th ed. combines tumor (T), regional lymph node (N), and distant metastasis (M) staging to determine an overall stage of II, III, or IV, ranging from least to most advanced, respectively. Stage II: T2/N0/M0; Stage III: T3/N0/M0 or T1-3/N1/M0; Stage IV: T4a/N0-1/M0 or T4b/any N/M0 or any T/N2-3/M0. The higher the number after the T, the larger the tumor or the more it has grown into nearby tissues. The higher the number after the N, the greater the involvement of regional lymph nodes. M0 indicates no distant metastasis.

Overall stage

A total of 69 progression-free survival (PFS) were required. As of September 13, 2020, the number of observed PFS events was 66. At the Radiation Therapy Oncology Group Foundation Data Monitoring Committee meeting on October 22, 2020, a decision was made to report the final results using data through November 30, 2020. This decision has a minor impact (\<1%) on the power given that 67 PFS events are included in the final analysis of this trial.

Wendy Seiferheld

Hazard ratio (lapatinib/placebo) set at 0.65 (35% reduction), 1-sided alpha 0.20 (final test at 0.1803 accounting for 1 interim analysis), logrank test, 80% power, 69 events in 128 randomized (142 total enrolled) patients required. Final analysis at 67 (of 69) events drops power to 79%.

Percentage of Participants Alive Without Progression (Progression-free Survival)

Percentage of Participants Alive (Overall Survival)

Percentage of Participants With Distant Metastases

Participants Who Started Protocol Treatment

Percentage of Participants With Treatment-related Grade 3 or Higher Adverse Events

Pre-IMRT lapatinib/placebo

Concurrent lapatinib/placebo

Maintenance lapatinib/placebo

Percentage of Participants Who Complied With Protocol Treatment

Percentage of Participants With Local-regional Progression

Performance Status Scale for Head & Neck Cancer.

Functional Assessment of Cancer Therapy - Head & Neck.

University of Michigan Xerostomia-Related Quality of Life Scale.

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

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

No assays were performed, and no data were collected for this outcome measure. Specimen use will require funding separate from this trial.

Spots Global Cancer Trial Database for TRYHARD: Radiation Therapy Plus Cisplatin With or Without Lapatinib in Treating Patients With Head and Neck Cancer.

Trial Identification

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Study Description

Keywords

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