Clinical trial NCT04759664: LUT014 for the Reduction of Dose-Limiting Acneiform Lesions Associated With EGFRI Treatment of mCRC
Official title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study of Topically Administered LUT014 in Metastatic Colorectal Cancer Patients With EGFR Inhibitor Induced Acneiform Lesions
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: EGFRI Induced Acneiform Lesions
Keywords: EGFRI, Acneiform, Acneiform lesions, Acneiform rash, EGFRI induced skin toxicities
Lead sponsor: Lutris Pharma Ltd.
Sponsor class: INDUSTRY
First posted: 2021-02-18
Enrollment: 117
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study evaluates the efficacy and safety of two strengths of LUT014 Gel topically applied once a day for 4 weeks, compared to placebo, in metastatic colorectal cancer (mCRC) patients who developed Grade 2 or non-infected Grade 3 EGFRI induced acneiform lesions


Eligibility criteria: Inclusion Criteria:

1. Diagnosed with mCRC;
2. Currently being treated with an FDA approved monoclonal antibody EGFRI for the treatment of mCRC, including but not limited to Erbitux® (cetuximab) Injection and Vectibix® (panitumumab) Injection, as directed by the approved labeling;
3. Grade 2 or Grade 3 non-infected acneiform lesions at the Screening and Baseline;
4. A reversed score of no more than 44 for the skin-specific questions (first 13 questions) of the FACT-EGFRI-18 HRQoL questionnaire at the Screening and Baseline;
5. Age ≥18 years at the time of signing the informed consent form (ICF);
6. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2;
7. Expected life expectancy greater than 3 months;
8. Subject can understand and sign the ICF, can communicate with the Investigator, can understand and comply with the requirements of the protocol, and can apply the study drug by himself/herself or has a care giver that can apply the drug;
9. Women of childbearing potential (WCBP) must have a negative serum pregnancy test at Screening and a negative urine pregnancy test at Baseline (Day 0);

Exclusion Criteria:

1. Active infection within the treatment area or in other body areas that requires initiation of systemic antibiotics ;
2. Significant skin disease other than EGFRI induced acneiform lesions within the same body areas planned for study drug application;
3. Has a beard that would interfere with administration of study drug and assessment of study endpoints (scoring of lesions);
4. Any cancer other than mCRC within 3 years of Screening, except for carcinoma in situ of the cervix;
5. Any condition which, in the opinion of the Investigator, places the subject at unacceptable risk if he/she were to participate in the study;
6. Clinically relevant serious co-morbid medical conditions including, but not limited to, unstable angina, symptomatic congestive heart failure, uncontrolled hypertension, uncontrolled cardiac arrhythmias, chronic obstructive or chronic restrictive pulmonary disease, active central nervous system (CNS) disease uncontrolled by standard of care, known positive status for human immunodeficiency virus (HIV) and/or active hepatitis B or C, cirrhosis, or psychiatric illness/social situations that would limit compliance with study requirements;
7. Pregnant or lactating;
8. Treatment with an EGFRI other than the FDA approved monoclonal antibody EGFRI for the treatment of mCRC within 30 days or 5 half-lives of the drug prior to Screening, whichever is longer;
9. Treatment with a serine/threonine-protein kinase B-Raf (B-Raf) inhibitor, including but not limited to Zelboraf® (vemurafenib), Tafinlar® (dabrafenib), Braftovi® (encorafenib), and Nexavar® (sorafenib), within 30 days or 5 half-lives of the drug prior to Screening, whichever is longer. Patients whose mCRC is being treated with a monoclonal antibody EGFRI in combination with a B-Raf inhibitor, such as Erbitux® (cetuximab) Injection in combination with Braftovi® (encorafenib) Capsules, will not be eligible to participate in this trial;
10. Treatment with a systemic corticosteroid 14 days prior to Baseline or treatment with a topical corticosteroid to the face, neck, or upper portion of the anterior or posterior chest within 7 days prior to Baseline (Day 0). Patients receiving systemic corticosteroids for 24 hours or less only at the time of chemotherapy infusions (for the prevention or treatment of chemotherapy-induced nausea and vomiting) will be allowed to enroll into this study;
11. Treatment with a topical antibiotic to the face, neck, or upper portion of the anterior or posterior chest within 7 days prior to Baseline (Day 0);
12. Initiation of treatment with systemic antibiotic(s) \< 28 days prior to Baseline (Day 0) or any change in dose or frequency of systemic antibiotic(s) within 28 days prior to Baseline. Patients that undergo a washout from systemic antibiotic(s) will be allowed to participate in this trial as long as no systemic antibiotics are taken within 7 days prior to Baseline and they meet all other eligibility criteria;
13. Treatment with any other topical medication applied to the face, neck, or upper portion of the anterior or posterior chest within 7 days prior to Baseline (Day 0).
14. Treatment with an oral retinoid within 30 days or 5 half-lives of the drug prior to Baseline (Day 0), whichever is longer. Patients that undergo a washout from oral retinoids will be allowed to participate
15. Treatment with another investigational drug within 30 days or 5 half-lives of drug prior to Screening, whichever is longer;
16. Known hypersensitivity to the inactive ingredients of the study drug (active or placebo).

Primary outcomes:
measure: The proportion of subjects in each treatment group who reached treatment success
timeFrame: Four weeks (28 days)
Secondary outcomes:
measure: Change in the severity of acneiform lesions based on CTCAE grading scale from baseline to Days 7, 14, 21, 28, and 55. For subjects enrolled in the OLE, the change from pre-dose Day 28 to Days 35, 42, 49, 56, and 84 will also be evaluated;
timeFrame: 8-16 weeks (56-84 days)
measure: Change in the FACT-EGFRI-18 questionnaire total score for the skin-specific questions from baseline to Days 7, 14, 21, 28, and 55. For subjects enrolled in the OLE, the change from pre-dose Day 28 to Days 35, 42, 49, 56, and 84 will also be evaluated;
timeFrame: 8 -16 weeks (56-84 days)
measure: Relative change in the FACT-EGFRI-18 HRQoL questionnaire
timeFrame: 8 weeks (56 days)
measure: Proportion of subjects whose dose of EGFRI was decreased, delayed, or stopped during the RDPBC and the OLE treatment period
timeFrame: 4 weeks (28 days)
measure: Number of AEs and the number and percentage of subjects with AEs
timeFrame: 8 weeks (6 days)
Other outcomes:
Locations:
city: Glendale
country: United States
facility: Innovative Clinical Research Institute
state: California
city: Santa Monica
country: United States
facility: UCLA
state: California
city: Miami
country: United States
facility: Miami Dermatology & Laser Research
state: Florida
city: Miami
country: United States
facility: Miami Dermatology and Laser Institute
state: Florida
city: Tampa
country: United States
facility: Moffit Cancer Center
state: Florida
city: Hazard
country: United States
facility: Appalachian Regional Healthcare
state: Kentucky
city: Shreveport
country: United States
facility: Willis-Knighton Cancer Center
state: Louisiana
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Neptune
country: United States
facility: Hackensack Meridian Health
state: New Jersey
city: New York
country: United States
facility: Memorial Sloane Kettering
state: New York
city: New York
country: United States
facility: New York Cancer and Blood Specialists
state: New York
city: Cincinnati
country: United States
facility: The Christ Hospital
state: Ohio
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center Investigational Drug Service
state: Pennsylvania
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Everett
country: United States
facility: Providence Regional Cancer Partnership
state: Washington
city: Tacoma
country: United States
facility: MultiCare Institute for Research and Innovation
state: Washington
city: Ashdod
country: Israel
facility: Assuta Ashdod
city: H̱olon
country: Israel
facility: E. Wolfson Medical Center
city: Jerusalem
country: Israel
facility: Shaara Zedek Medical Center
Study officials:
References: