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

NCT06120140
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Phase
Phase 2
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Recruitment status
Active, not recruiting
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Participants
305
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Lead sponsor
Janssen Research & Development, LLC
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Start date
2024-02-16
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Number of sites
93
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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 and with modified enhanced dermatologic 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. The study also includes Expansion cohorts (in 2 different schedules) to evaluate enhanced dermatologic management and early intervention for DAEIs or paronychia, in participants receiving subcutaneous amivantamab and lazertinib. A substudy will enroll participants from Arms A and B who experience specific new-onset or persistent DAEIs (Grade \>=2) during treatment with intravenous (IV) amivantamab and lazertinib. This substudy aims to assess the reactive use of dermatologic treatment strategies in these participants.
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Acronym
COCOON
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Short title
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
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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
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Control arm
Active comparator
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Active, not recruiting
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Phase
Phase 2
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Study type
Interventional
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Completion date
2030-06-30
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First posted
2023-11-07
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Registry last updated
2026-08-28
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Primary completion date
2027-05-31
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Start date
2024-02-16
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Actual participants
305
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Participants
305
clinicaltrials.gov
Participant count basis
Actual
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Protocol amendments
13
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Number of sites
93
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Data monitoring committee
Yes
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Registry sponsor category
Industry
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Lead sponsor
Janssen Research & Development, LLC
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Source registry
ClinicalTrials.gov
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Registry ID
NCT06120140
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ClinicalTrials.gov ID
NCT06120140
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Registry record
Open registry record
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Allocation
Randomised
Model
Parallel groups
Purpose
Treatment
Masking
No masking
Sources for study design
clinicaltrials.gov

  1. 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

    Timeframe: Up to 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.

  1. Number of Participants With DAEIs by Severity Based on NCI-CTCAE v 5.0

    Timeframe: Up to 12 weeks after initiation of anticancer treatment

    Number of participants with DAEIs by severity based on NCI-CTCAE v 5.0 will be reported.

  2. Number of Participants With Grade >=2 DAEIs Within 6 Months After Initiation of Anticancer Treatment Based on NCI-CTCAE v 5.0

    Timeframe: Up to 6 months after initiation of anticancer treatment

    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.

  3. Number of Grade >= 2 DAEI Per Participants

    Timeframe: Up to 12 months

    Number of grade \>= 2 DAEI per participants will be reported.

  4. Time to First Occurrence of Grade >=2 DAEI

    Timeframe: Up to 12 months

    Time to first occurrence of Grade \>=2 DAEI will be reported.

  5. Time to Resolution of Grade >= 2 DAEI

    Timeframe: Up to 12 months

    Time to resolution of Grade \>= 2 DAEI will be reported.

  6. Number of Participants With Paronychia by Severity Based on NCI-CTCAE v 5.0

    Timeframe: Up to 6 months after initiation of anticancer treatment

    Number of participants with paronychia by severity based on NCI-CTCAE v 5.0 will be reported.

  7. Number of Participants With Scalp Rash by Severity Based on NCI-CTCAE v 5.0

    Timeframe: Up to 12 months after initiation of anticancer treatment

    Number of participants with scalp rash by severity based on NCI-CTCAE v 5.0 will be reported.

  8. Change From Baseline in Skindex Symptoms Domain Score up to 12 Months

    Timeframe: Baseline, up to Month 12

    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.

  9. Change From Baseline in Patient's Global Impression-Severity (PGI-S) Rash up to 12 Months

    Timeframe: Baseline, up to Month 12

    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.

  10. 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

    Timeframe: Baseline, up to Month 12

    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.

  11. Change From Baseline in EuroQol 5 - Dimension (EQ-5D) Patient-reported Outcome (PRO) up to 12 Months (for Amivantamab Subcutaneous Expansion Cohort Only)

    Timeframe: Baseline, up to Month 12

    The EQ-5D questionnaire is a brief, generic HRQOL assessment that can that can also be used to incorporate participant preferences into health economic evaluations. The EQ-5D questionnaire assesses HRQOL in terms of degree of limitation on 5 health dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) and as overall health using a visual analog scale with response options ranging from 0 (worst imaginable health) to 100 (best imaginable health). Lower scores indicate worsening. EQ-5D scores include EQ-5D valuation index score (a weighted scoring of the 5 dimension scores with a possible range from 0 to 1), EQ-5D visual analog scale (VAS) is a vertical VAS with scores ranging from 0 (worst imaginable health) to 100 (perfect health), and EQ5D descriptive system scores (five scores reflecting each of the 5 EQ-5D health dimensions ranging from 0 \[no limitation\] to 4 \[incapacity\]).

  12. Percentage of Participants With Dose Reductions, Dose Interruptions, and Dose Discontinuations of Anticancer Treatment due to DAEIs

    Timeframe: Up to 12 months

    Percentage of participants with dose reductions, dose interruptions, and dose discontinuations of anticancer treatment due to DAEIs will be reported.

  13. Relative Dose Intensity (RDI) of Anticancer Treatment

    Timeframe: Up to 12 months

    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.

  14. Percentage of Participants With Venous Thromboembolism (VTE) Adverse Events (AEs) by Severity Based on NCI-CTCAE v 5.0

    Timeframe: Up to 12 months

    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.

  15. Percentage of Participants With Adverse Events (AEs) by Severity Based on NCI-CTCAE v 5.0

    Timeframe: Up to 12 months

    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.

  16. Progression Free Survival (PFS)

    Timeframe: Up to 12 months

    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.

  17. Overall Response Rate (ORR)

    Timeframe: Up to 12 months

    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.

  18. Duration of Response (DoR)

    Timeframe: Up to 12 months

    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.

  19. Amivantamab SC Expansion Cohorts: Number of Participants With Grade >= 2 DAEIs Within 12 Weeks After Initiation of Anticancer Treatment

    Timeframe: Up to 12 weeks after initiation of anticancer treatment

    Participants with Grade \>= 2 DAEIs within 12 weeks after initiation of anticancer treatment based on NCI-CTCAE 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.

  20. Amivantamab SC Expansion Cohorts: Percentage of Participants With an Improvement in DAEI After Starting Early Intervention

    Timeframe: Up to 12 months

    Percentage of participants showing an improvement in DAEI by a minimum of 1 NCI-CTCAE grade after starting early intervention will be reported. 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.

  21. Amivantamab SC Expansion Cohorts: Time to Improvement of DAEIs After Starting Early Intervention

    Timeframe: Up to 12 months

    Time to improvement of DAEIs by a minimum of 1 NCI-CTCAE grade after starting early intervention will be reported. 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.

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

  • Have histologically or cytologically confirmed, locally advanced or metastatic non-small cell lung cancer (NSCLC); Is treatment naive and not amenable to curative therapy including surgical resection or (chemo) radiation. Adjuvant or neoadjuvant therapy for Stage I, Stage II or Stage IIIA disease is allowed if last dose 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
  • A participant with asymptomatic or previously treated and stable brain metastases may participate in this study. Participants with a history of symptomatic 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). For the amivantamab SC expansion cohorts: Due to the increased risk of skin cancer with ruxolitinib, participants with any prior or concurrent skin malignancies will be excluded
  • Sub-study: Participants must have new-onset or persistent (defined as non-responsive to standard of care [SoC]) Grade >=2 specific DAEIs of the scalp, face, or body, as defined by NCI-CTCAE Grading v5.0 for DAEIs (excluding paronychia)

  • 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). For the amivantamab SC expansion cohorts, this includes active localized serious infections; 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, timolol*, ruxolitinib*, zinc*, corticosteroids* or their excipients or to any component of the enhanced dermatologic management (*for the amivantamab SC expansion cohorts)
  • Participant has received any prior systemic treatment at any time for locally advanced stage III B/C or metastatic stage IV disease (adjuvant or neoadjuvant therapy for stage I, II or IIIA disease is allowed if last dose 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
  • Sub-study: Participants who have received prior treatment for epidermal growth factor receptor (EGFR)-induced DAEIs with JAK inhibitors (for Cohort A) or calcineurin inhibitors (for Cohort B)
Sources for eligibility
clinicaltrials.gov

  • Ironwood Cancer and Research CenterChandler, United States
  • City of HopeDuarte, United States
  • Providence FullertonFullerton, United States
  • Los Angeles Cancer NetworkGlendale, United States
  • City of Hope SeacliffHuntington Beach, United States
  • City of Hope Orange County Lennar Foundation Cancer CenterIrvine, United States
  • City of Hope Long Beach ElmLong Beach, United States
  • Cancer and Blood Specialty ClinicLos Alamitos, United States
  • Keck Hospital of USCLos Angeles, United States
  • USC Norris Oncology Hematology Newport BeachNewport Beach, United States
  • Kaiser Permanente Oakland Medical CenterOakland, United States
  • Kaiser Permanente Roseville Medical CenterRoseville, United States
  • Kaiser Permanente San Francisco Medical CenterSan Francisco, United States
  • Kaiser Permanente Santa Clara Medical CenterSanta Clara, United States
  • City of Hope South PasadenaSouth Pasadena, United States
  • Kaiser Permanente Northern CaliforniaVallejo, United States
  • Kaiser Permanente Walnut Creek Medical CenterWalnut Creek, United States
  • University Cancer & Blood CenterAthens, United States
  • Hope and Healing CareHinsdale, United States
  • Oncology Hematology AssociatesSpringfield, United States
  • Renown Health Medical OncologyReno, United States
  • Hunterdon Hematology OncologyFlemington, United States
  • Clinical Research Alliance IncWestbury, United States
  • Regional Medical Oncology CenterWilson, United States
  • University Hospitals Cleveland Medical CenterCleveland, United States

And 68 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

  • 2023
  • 2023-505863-35-00
  • 61186372NSC2007
Sources for references
clinicaltrials.gov

Related records

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