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

NCT01711658 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: RF-3501LAP116153
• Study Type: interventional
• Target: 142
• Locations: 2 countries
• Sites: 16

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

Outcome Measures

Primary Outcomes (1)

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

  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.

  From randomization to last follow-up. Maximum follow-up at time of analysis was 7.1 years.

Secondary Outcomes (9)

• Percentage of Participants Alive (Overall Survival)

  From randomization to last follow-up. Maximum follow-up at time of analysis was 7.1 years.

• Percentage of Participants With Distant Metastases

  From randomization to last follow-up. Maximum follow-up at time of analysis was 7.1 years.

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

  From start of treatment to last follow-up. Maximum follow-up at time of analysis was 7.1 years.

• Percentage of Participants Who Complied With Protocol Treatment

  From start of treatment to end of treatment (approximately 5 months from randomization).

• Percentage of Participants With Local-regional Progression

  From randomization to last follow-up. Maximum follow-up at time of analysis was 7.1 years.

Study Arms (2)

IMRT + cisplatin + placebo

PLACEBO COMPARATOR

Intensity Modulated Radiation Therapy (IMRT) with cisplatin and placebo

Radiation: IMRT; Drug: Cisplatin; Drug: placebo

IMRT + cisplatin + lapatinib

ACTIVE COMPARATOR

IMRT with cisplatin and lapatinib

Radiation: IMRT; Drug: Cisplatin; Drug: Lapatinib

Interventions

IMRT 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

IMRT + cisplatin + lapatinib; IMRT + cisplatin + placebo

Cisplatin DRUG

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

IMRT + cisplatin + lapatinib; IMRT + cisplatin + placebo

placebo 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 + placebo

Lapatinib 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

IMRT + cisplatin + lapatinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Radiation Therapy Oncology Group: lead
• GlaxoSmithKline: collaborator
• Novartis: collaborator

Study Sites (16)

University of Alabama at Birmingham Comprehensive Cancer Center

Birmingham, Alabama, 35294, United States

Location

University of California, San Diego

La Jolla, California, 92093, United States

Location

Sutter General Hospital

Sacramento, California, 95816, United States

Location

University of California San Francisco

San Francisco, California, 94143, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

Emory University

Atlanta, Georgia, 30308, United States

Location

James Graham Brown Cancer Center at University of Louisville

Louisville, Kentucky, 40202, United States

Location

University Hospitals of Cleveland

Cleveland, Ohio, 44106, United States

Location

Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73190, United States

Location

Fox Chase Cancer Center Buckingham

Furlong, Pennsylvania, 18925, United States

Location

University of Texas Southwestern Medical School

Dallas, Texas, 75390, United States

Location

University of Texas - MD Anderson Cancer Center

Houston, Texas, 77030-4009, United States

Location

University of Wisconsin Comprehensive Cancer Center

Madison, Wisconsin, 53792, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

McGill Cancer Centre at McGill University

Montreal, Quebec, H2W 1S6, Canada

Location

Related Publications (3)

• 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.

  PMID: 20530316 BACKGROUND

• 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

  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.

  PMID: 37768670 DERIVED

MeSH Terms

Conditions

Head and Neck Neoplasms

Interventions

Cisplatin; Lapatinib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

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.

Results Point of Contact

• Title: Wendy Seiferheld
• Organization: NRG Oncology

seiferheldw@nrgoncology.org

215-574-3208

Study Officials

• Stuart Wong, MD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 16, 2012
• First Posted: October 22, 2012
• Study Start: March 15, 2013
• Primary Completion: December 1, 2020
• Study Completion: September 21, 2022
• Last Updated: October 17, 2023
• Results First Posted: November 29, 2021

Record last verified: 2021-10

Locations

US (15); CA (1)