A Study of LUT014 in Patients With Metastatic Colorectal Cancer With EGFR Inhibitor Induced Acneiform Lesions

• ClinicalTrials.gov Identifier: NCT03876106
• Recruitment Status: Completed
• First Posted: March 15, 2019
• Last Update Posted: April 6, 2022
• Sponsor: Lutris Pharma Ltd.
• Information provided by (Responsible Party): Lutris Pharma Ltd.

Tracking Information

• First Submitted Date: March 11, 2019
• First Posted Date: March 15, 2019
• Last Update Posted Date: April 6, 2022
• Actual Study Start Date: August 21, 2019
• Actual Primary Completion Date: July 9, 2020 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: March 12, 2019): Safety and tolerability (maximum tolerated dose, MTD) of LUT014 topically applied qd for 4 weeks in metastatic colorectal cancer (mCRC) patients with epidermal growth factor receptor inhibitor (EGFRI) induced acneiform lesions. [ Time Frame: From Day 0 (following administration of the first dose of study drug) through the Day 55 ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 14, 2019)

• Maximum concentration (Cmax) in plasma after a single administration and after qd administrations for 8 days [ Time Frame: Pre-dose through Day 8 ]
• Time to maximum concentration (Tmax) in plasma after a single administration and after qd administrations for 8 days [ Time Frame: Pre-dose through Day 8 ]
• Area under the concentration-time curve from time zero to last measurable concentration (AUC0-T) [ Time Frame: Pre-dose through Day 8 ]
• Area under the concentration-time cure from time zero extrapolated to infinity (AUC0-∞) [ Time Frame: Pre-dose through Day 8 ]
• Plasma elimination half-life (t1/2) [ Time Frame: Pre-dose through Day 8 ]
• Plasma clearance (CL) [ Time Frame: Pre-dose through Day 8 ]
• Volume of distribution (Vd) [ Time Frame: Pre-dose through Day 8 ]
• NCI, Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 skin and subcutaneous tissue disorders grading scale performed locally by the Investigator [ Time Frame: Pre-dose through Day 55 ]
  The scale contains 5 grades from 1 which demonstrates the mild form of the disease up to 5, defined as death.
• MASCC Study Group EGFRI-dermatologic AE grading by central reader based on photographs [ Time Frame: Pre-dose through Day 55 ]
• Functional Assessment of Cancer Therapy-EGFRI 18 (FACT-EGFRI-18) on health-related quality of life (HRQoL) questionnaire [ Time Frame: Pre-dose through Day 55 ]
  FACT-EGFRI-18 is a patient-reported outcomes questionnaire developed to assess the effect of EGFRI on health-related quality of life The questionnaire includes 18 questions, each should be graded from 0, not suffering from this side effect at all, up to 4, suffering greatly from this side effect

Original Secondary Outcome Measures (submitted: March 12, 2019)

• Maximum concentration (Cmax) in plasma after a single administration and after qd administrations for 8 days [ Time Frame: Pre-dose through Day 8 ]
• Time to maximum concentration (Tmax) in plasma after a single administration and after qd administrations for 8 days [ Time Frame: Pre-dose through Day 8 ]
• Area under the concentration-time curve from time zero to last measurable concentration (AUC0-T) [ Time Frame: Pre-dose through Day 8 ]
• Area under the concentration-time cure from time zero extrapolated to infinity (AUC0-∞) [ Time Frame: Pre-dose through Day 8 ]
• Plasma elimination half-life (t1/2) [ Time Frame: Pre-dose through Day 8 ]
• Plasma clearance (CL) [ Time Frame: Pre-dose through Day 8 ]
• Volume of distribution (Vd) [ Time Frame: Pre-dose through Day 8 ]
• NCI CTCAE Version 5.0 skin and subcutaneous tissue disorders grading scale performed locally by the Investigator [ Time Frame: Pre-dose through Day 55 ]
• MASCC Study Group EGFRI-dermatologic AE grading by central reader based on photographs [ Time Frame: Pre-dose through Day 55 ]
• FACT-EGFRI-18 HRQoL questionnaire [ Time Frame: Pre-dose through Day 55 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of LUT014 in Patients With Metastatic Colorectal Cancer With EGFR Inhibitor Induced Acneiform Lesions
• Official Title: A Phase 1, Open-Label, Dose Escalation Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy Study of Topically Administered LUT014 in Metastatic Colorectal Cancer Patients With EGFR Inhibitor Induced Acneiform Lesions
• Brief Summary: The purpose of this phase 1, multicenter study is to evaluate the safety, tolerability and preliminary efficacy of LUT014 in adult metastatic colorectal cancer patients with EGFR Inhibitor induced acneiform lesions
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1

Study Design

Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

3+3 Dose escalation of LUT014

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: EGFR Inhibitor Induced Acneiform Lesions

Intervention

Drug: LUT014

Topical

Study Arms

• Experimental: LUT014 dose level 1
  LUT014 will be topically applied to the face, neck, and upper portion of the anterior and posterior chest once a day for 4 weeks.
  Intervention: Drug: LUT014
• Experimental: LUT014 dose level 2
  LUT014 will be topically applied to the face, neck, and upper portion of the anterior and posterior chest once a day for 4 weeks.
  Intervention: Drug: LUT014
• Experimental: LUT014 dose level 3
  LUT014 will be topically applied to the face, neck, and upper portion of the anterior and posterior chest once a day for 4 weeks.
  Intervention: Drug: LUT014

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 7, 2020): 10
• Original Estimated Enrollment (submitted: March 12, 2019): 9
• Actual Study Completion Date: November 18, 2020
• Actual Primary Completion Date: July 9, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Diagnosed with mCRC;
• Currently being treated with an FDA approved EGFRI for the treatment of mCRC, including but not limited to Erbitux® (cetuximab) Injection and Vectibix® (panitumumab) Injection, as directed by the approved labeling;
• Treatment with the FDA approved EGFRI initiated within 12 weeks prior to the Screening Visit;
• Grade 1 or 2 acneiform lesions at the Screening and Baseline (Day 0) Visits; A minimum of 3 subjects per dose cohort must have Grade 2 non-infected acneiform lesions at the Screening and Baseline (Day 0) Visits;
• Age ≥18 years at the time of signing the informed consent form (ICF);
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2;
• Expected life expectancy greater than 3 months;
• 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;
• Women of childbearing potential (WCBP) must have a negative serum pregnancy test at Screening and a negative urine pregnancy test at baseline (Day 0);
• WCBP must agree to abstain from sex or use an adequate method of contraception from the time of informed consent through the Day 55 Visit and for 90 days after the last dose of study drug (LUT014);
• Males must abstain from sex with WCBP or use an adequate method of contraception from the time of informed consent through the Day 55 Visit and for 90 days after the last dose of study drug (LUT014).

Exclusion Criteria:

• Active infection;
• Significant skin disease other than EGFRI induced acneiform lesions;
• Any cancer other than mCRC within 3 years of Screening;
• Any condition which, in the opinion of the Investigator, places the subject at unacceptable risk if he/she were to participate in the study;
• 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;
• Pregnant or lactating;
• Treatment with an EGFRI other than those specified in the inclusion criteria within 30 days or 5 half-lives of the drug prior to Screening, whichever is longer;
• Treatment with a serine/threonine-protein kinase B-Raf (B-Raf) inhibitor, including but not limited to Zelboraf® (vemurafenib), Tafinlar® (dabrafenib), BraftoviTM (encorafenib), and Nexavar® (sorafenib), within 30 days or 5 half-lives of the drug prior to Screening, whichever is longer;
• Treatment with a systemic antibiotic within 7 days prior to Screening;
• Treatment with a topical corticosteroid to the face, neck, or upper portion of the anterior or posterior chest within 14 days prior to Screening or treatment with a systemic corticosteroid within 14 days prior to Screening, except for low dose systemic corticosteroids (e.g., 8-20 mg dexamethasone or comparable) given for up to one or two days every two weeks as part of standard of care for the prevention or treatment of chemotherapy-induced nausea and vomiting (CINV) for subjects being treated with FDA-approved EGFRI and chemotherapy combinations for mCRC;
• Treatment with an oral retinoid within 7 days prior to Screening;
• Treatment with another investigational drug within 30 days or 5 half-lives of drug prior to Screening, whichever is longer;
• Known hypersensitivity to the inactive ingredients of the study drug (LUT014).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Israel, United States

Administrative Information

• NCT Number: NCT03876106
• Other Study ID Numbers: L-01-01
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Lutris Pharma Ltd.
• Original Responsible Party: Same as current
• Current Study Sponsor: Lutris Pharma Ltd.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Lutris Pharma Ltd.
• Verification Date: April 2022