Enhanced Dermatological Care to Reduce Rash and Paronychia in Epidermal Growth Factor Receptor (EGRF)-Mutated Non-Small Cell Lung Cancer (NSCLC) Treated First-line With Amivantamab Plus Lazertinib

Carcinoma, Non-Small-Cell Lung Clinical Trial

— COCOON  

Official title:

A Phase 2, Open-Label, Randomized Trial Evaluating the Impact of Enhanced Versus Standard Dermatologic Management on Selected Dermatologic Adverse Events Among Patients With Locally Advanced or Metastatic EGFR-Mutated NSCLC Treated First-Line With Amivantamab + Lazertinib

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06120140
• Other study ID #: 61186372NSC2007
• Secondary ID: 2023-505863-35-0
• Status: Recruiting
• Phase: Phase 2
• Start date: February 16, 2024
• Est. completion date: March 31, 2026

Study information

• Verified date: June 2024
• Source: Janssen Research & Development, LLC
• Contact: Study Contact
• Phone: 844-434-4210
• Email: Participate-In-This-Study[@]its.jnj.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate whether enhanced dermatologic management can reduce incidence of grade greater than or equal to (>=) 2 dermatologic adverse events of interest (DAEIs) when compared with standard-of-care skin management in participants with locally advanced or metastatic stage IIIB/C-IV epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) treated first-line with amivantamab and lazertinib.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: March 31, 2026
• Est. primary completion date: July 3, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Have histologically or cytologically confirmed, locally advanced or metastatic non-small cell lung cancer (NSCLC) that is treatment-naive and not amenable to curative therapy including surgical resection or (chemo) radiation. Adjuvant or neoadjuvant therapy for Stage I or Stage II disease is allowed if administered more than 12 months prior to the development of locally advanced or metastatic disease
• Have a tumor that harbors an epidermal growth factor receptor (EGFR) exon 19del or exon 21 L858R substitution, as detected by an Food and Drug Administration (FDA)-approved or other validated test in a clinical laboratory improvement amendments (CLIA)-certified laboratory (sites in the United States) or an accredited local laboratory (sites outside of the United States) in accordance with site standard of care
• Participants with a history of brain metastases must have had all lesions treated as clinically indicated (that is, no current indication for further definitive local therapy). Any definitive local therapy to brain metastases must have been completed at least 14 days prior to randomization, and the participant can be receiving no greater than 10 milligram (mg) prednisone or equivalent daily for the treatment of intracranial disease
• Can have prior or concurrent second malignancy (other than the disease under study)which natural history or treatment is unlikely to interfere with any study endpoints, safety, or the efficacy of the study treatment(s)
• Have an eastern cooperative oncology group (ECOG) performance status of 0 to 1

Exclusion Criteria:

• History of uncontrolled illness, including but not limited to uncontrolled diabetes; ongoing or active infection (includes infection requiring treatment with antimicrobial therapy [participants will be required to complete antibiotics 1 week prior to starting background anticancer treatment] or diagnosed or suspected viral infection); active bleeding diathesis; impaired oxygenation requiring continuous oxygen supplementation; refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of background anticancer treatment or doxycycline/minocycline; psychiatric illness, social situation, or any other circumstances that would limit compliance with study requirements; any ophthalmologic condition that is clinically unstable; pre-existing skin condition that would prevent adequate evaluations of dermatologic toxicity, as determined by the investigator
• Medical history of interstitial lung disease (ILD), including drug-induced ILD or radiation pneumonitis
• Known allergy, hypersensitivity, or intolerance to the excipients of amivantamab, lazertinib, or to tetracyclines, doxycycline, minocycline, or their excipients or to any component of the enhanced dermatologic management
• Participant has received any prior systemic treatment at any time for locally advanced stage III or metastatic stage IV disease (adjuvant or neoadjuvant therapy for stage I or II disease is allowed if administered more than 12 months prior to the development of locally advanced or metastatic disease)
• Participant has an active or past medical history of leptomeningeal disease

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung

Intervention

Drug:
• Amivantamab
Amivantamab will be administered as intravenous (IV) infusion.
• Lazertinib
Lazertinib tablet will be administered orally.
• Doxycycline
Doxycycline tablet will be administered orally.
• Minocycline
Minocycline capsule will be administered orally.
• Clindamycin
Clindamycin lotion will be used as topical application on the scalp.
• Chlorhexidine
Chlorhexidine solution will be used as topical application on hands and feet.

Other:
• Noncomedogenic skin moisturizer
Noncomedogenic skin moisturizer will be used as topical application.

Locations

Country	Name	City	State
Argentina	Hospital Italiano de Buenos Aires	Buenos Aires
Argentina	IADT Instituto Argentino de Diagnostico y Tratamiento	Caba
Argentina	Centro Medico Austral	Capital Federal
Argentina	Hospital Italiano de La Plata	La Plata
Argentina	Hospital Privado de la Comunidad	Mar del Plata
Brazil	Fundacao Doutor Amaral Carvalho	Jaú
Brazil	Fundacao Antonio Prudente A C Camargo Cancer Center	Sao Paulo
Brazil	Associacao Feminina de Educacao e Combate ao Cancer Hospital Santa Rita de Cassia	Vitoria
China	Changzhou No 2 Peoples Hospital	Changzhou
China	West China Hospital	Chengdou
China	Sichuan Cancer Hospital	Chengdu
China	The First Affiliated Hospital Sun Yat sen University	Guang Zhou
China	Huizhou Municipal Central Hospital	Huizhou
China	Fudan University Shanghai Cancer Center	ShangHai
France	Hopital Nord	Marseille Cedex 20
France	Hopital PASTEUR	Nice
France	Institut Curie	Paris
Germany	Universitaetsklinikum der RWTH Aachen	Aachen
Germany	Kliniken Essen-Mitte	Essen
Germany	Universitaetsklinikum Giessen und Marburg GmbH	Giessen
Germany	Thoraxklinik am Universitatsklinikum Heidelberg	Heidelberg
Germany	Klinikum Kassel GmbH	Kassel
Korea, Republic of	Chungbuk National University Hospital	Cheongju-si
Korea, Republic of	Gachon University Gil Hospital	Incheon
Korea, Republic of	Severance Hospital Yonsei University Health System	Seoul
Malaysia	Hospital Pulau Pinang	Georgetown
Malaysia	University Malaya Medical Centre	Kuala Lumpur
Malaysia	Hospital Tengku Ampuan Afzan	Kuantan
Malaysia	Hospital Umum Sarawak	Kuching
Spain	Hosp. Univ. A Coruna	A Coruna
Spain	Hosp. Gral. Univ. de Alicante	Alicante
Spain	Hosp. Univ. Quiron Dexeus	Barcelona
Spain	Hosp. Univ. Vall D Hebron	Barcelona
Spain	Hosp. Univ. de Jaen	Jaen
Spain	Hosp. Univ. Lucus Augusti	Lugo
Spain	Hosp. Gral. Univ. Gregorio Maranon	Madrid
Spain	Hosp. Regional Univ. de Malaga	Malaga
Spain	Hosp. Ntra. Sra. de Valme	Sevilla
Taiwan	National Taiwan University Hospital Hsin Chu Branch	Hsin Chu
Taiwan	Chang Kung Memorial Hospital	Kaohsiung City
Taiwan	Taichung Veterans General Hospital	Taichung City
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Linkou Chang Gung Memorial Hospital	Taoyuan City
Turkey	Adana City Hospital	Adana
Turkey	Ankara Bilkent City Hospital	Ankara
Turkey	Gazi University Hospital	Ankara
Turkey	Gulhane Training and Research Hospital	Ankara
Turkey	I A U VM Medical Park Florya Hastanesi	Istanbul
Turkey	Ege University Medical Faculty	Izmir
Turkey	Ondokuz Mayis University	Samsun
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	City of Hope	Duarte	California
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	Hunterdon Hematology Oncology	Flemington	New Jersey
United States	Hope and Healing Care	Hinsdale	Illinois
United States	City of Hope Huntington Beach	Huntington Beach	California
United States	City of Hope Orange County Lennar Foundation Cancer Center	Irvine	California
United States	City of Hope Long Beach Elm	Long Beach	California
United States	Cancer and Blood Specialty Clinic	Los Alamitos	California
United States	Keck Hospital of USC	Los Angeles	California
United States	USC Norris Oncology Hematology Newport Beach	Newport Beach	California
United States	Renown Regional Medical Center	Reno	Nevada
United States	Valley Medical Center	Renton	Washington
United States	City of Hope South Pasadena	South Pasadena	California
United States	Oncology Hematology Associates	Springfield	Missouri
United States	Gundersen Health System	W. Salem	Wisconsin
United States	Clinical Research Alliance, Inc.	Westbury	New York
United States	Regional Medical Oncology Center	Wilson	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  China,  France,  Germany,  Korea, Republic of,  Malaysia,  Spain,  Taiwan,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Grade Greater Than or Equal to (>=) 2 Dermatologic Adverse Events of Interest (DAEIs) Within 12 Weeks After Initiation of Anticancer Treatment	Number of participants with Grade >= 2 DAEIs within 12 weeks after initiation of anticancer treatment based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 will be reported. DAEIs includes rash, dermatitis acneiform, pruritus, skin fissures, acne, folliculitis, erythema, eczema, rash maculo-papular, skin exfoliation, skin lesion, skin irritation, dermatitis, rash erythematous, rash macular, rash popular, rash pruritic, rash pustular, dermatitis contact, dermatitis exfoliative generalized, drug eruption, dyshidrotic eczema, eczema asteatotic and paronychia. As per NCI CTCAE v 5.0, severity scale ranges from Grade 1 (mild) to Grade 5 (death). Grade 1= mild, Grade 2= moderate, Grade 3= severe, Grade 4= life-threatening, and Grade 5= death related to adverse event.	Up to 12 weeks after initiation of anticancer treatment
Secondary	Number of Participants With DAEIs by Severity Based on NCI CTCAE v 5.0	Number of participants with DAEIs by severity based on NCI CTCAE v 5.0 will be reported.	Up to 12 weeks after initiation of anticancer treatment
Secondary	Number of Participants With Grade >=2 DAEIs Within 6 Months After Initiation of Anticancer Treatment Based on NCI CTCAE v 5.0	Number of participants with Grade >=2 DAEIs within 6 months after initiation of anticancer treatment based on NCI CTCAE v 5.0 will be reported.	Up to 6 months after initiation of anticancer treatment
Secondary	Time to First Occurrence of Grade >=2 DAEI	Time to first occurrence of Grade >=2 DAEI will be reported.	Up to 12 months
Secondary	Number of Participants With Paronychia by Severity Based on NCI CTCAE v 5.0	Number of participants with paronychia by severity based on NCI CTCAE v 5.0 will be reported.	Up to 6 months after initiation of anticancer treatment
Secondary	Number of Participants With Scalp Rash by Severity Based on NCI CTCAE v 5.0	Number of participants with scalp rash by severity based on NCI CTCAE v 5.0 will be reported.	Up to 12 months after initiation of anticancer treatment
Secondary	Change From Baseline in Skindex Symptoms Domain Score up to 12 Months	Change from baseline in skindex symptoms domain score up to 12 months will be reported. The score of quality of life will be assessed using the Skindex-16 questionnaire. Skindex-16 is used for participants to rate skin conditions.	Baseline, up to Month 12
Secondary	Change From Baseline in Patient's Global Impression-Severity (PGI-S) Rash up to 12 Months	Change from baseline in PGI-S rash up to 12 months will be reported. Participant quality of life will be evaluated using PGI-S Rash. PGI-S is a single-item questionnaire assessing participants disease severity on a 7-point response scale.	Baseline, up to Month 12
Secondary	Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) Score up to 12 Months	Change from baseline in EORTC-QLQ-C30 score up to 12 months will be reported. EORTC-QLQ-C30 is a core 30-item questionnaire for evaluating the health-related quality of life (HRQoL) of participants participating in cancer clinical studies.	Baseline, up to Month 12
Secondary	Percentage of Participants With Dose Reductions, Dose Interruptions, and Dose Discontinuations of Anticancer Treatment due to DAEIs	Percentage of participants with dose reductions, dose interruptions, and dose discontinuations of anticancer treatment due to DAEIs will be reported.	Up to 12 months
Secondary	Relative Dose Intensity (RDI) of Anticancer Treatment	Relative dose intensity of anticancer treatment will be reported. The relative dose intensity is defined as the ratio of total actually received dose versus total prescribed dose.	Up to 12 months
Secondary	Percentage of Participants With Venous Thromboembolism (VTE) Adverse Events (AEs) by Severity Based on NCI CTCAE v 5.0	Percentage of participants with VTE AEs (pulmonary embolism and deep vein thrombosis) by severity based on NCI CTCAE v 5.0 will be reported. An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention.	Up to 12 months
Secondary	Percentage of Participants With Adverse Events (AEs) by Severity Based on NCI CTCAE v 5.0	Percentage of participants with AEs by severity based on NCI CTCAE v 5.0 will be reported. An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention.	Up to 12 months
Secondary	Progression Free Survival (PFS)	PFS is defined as the time from the date of randomization to the date of first documented disease progression, as defined in the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, or death due to any cause, whichever occurs first.	Up to 12 months
Secondary	Overall Response Rate (ORR)	ORR is defined as the percentage of participants who achieve a partial response (PR) or better response using RECIST v1.1 as assessed by the investigator.	Up to 12 months
Secondary	Duration of Response (DoR)	DOR will be calculated among responders (with a PR or better response) from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease, as defined in the RECIST v1.1 response criteria.	Up to 12 months