LEAC-102 for Advanced Colorectal Cancer

A Phase I/IIa Dose-Escalation Study Evaluating the Safety, Tolerability and Efficacy of LEAC-102 in Combination With FOLFOX + Bevacizumab/Cetuximab in Subjects With Advanced Colorectal Cancer

A Phase I/IIa Dose-Escalation Study Evaluating the Safety, Tolerability and Efficacy of LEAC-102 in Combination with FOLFOX + Bevacizumab/Cetuximab in Subjects with Advanced Colorectal Cancer

Study Overview

• Status: Not yet recruiting
• Conditions: Advanced Colorectal Cancer
• Intervention / Treatment: Drug: LEAC-102 500mg capsule and FOLFOX + Bevacizumab/Cetuximab

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Cora Chen, Ph.D,; Phone Number: +886-978723555; Email: cora_chen@twleaderlife.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects aged at least 20 years old
2. Histologically or cytologically confirmed measurable and/or evaluable advanced (stage III/IV) colorectal cancer that can be accurately assessed by CT/MRI scan (RECIST v1.1) for which regimen of FOLFOX + Bevacizumab/Cetuximab is arranged by the investigator
3. Subjects may be treatment naïve, or may have received therapy for colorectal cancer.
4. ECOG performance status ≤ 2 and life expectancy ≥ 12 months Note: ECOG = Eastern Cooperative Oncology Group
5. Dated and signed informed consent

Exclusion Criteria:

1. Primary CNS malignancies or clinically active CNS metastases Note: CNS = central nervous system
2. Ascertained hypersensitivity to any component of investigational product or FOLFOX + Bevacizumab/Cetuximab that the subject will be treated

3. Any of the following hematologic abnormalities:

   1. Hemoglobin < 10.0 g/dL,
   2. ANC < 1,500/μL,
   3. Platelets < 100,000 /μL Note: ANC = absolute neutrophil count

4. Any of the following serum chemistry abnormalities:

   1. Total bilirubin > 1.5 × ULN,
   2. AST or ALT > 2.5 × ULN,
   3. Gamma-GT > 2.5 x ULN,
   4. Alk-P > 2.5 x ULN,
   5. serum albumin < 3.0 g/dL,
   6. creatinine > 1.5 × ULN,
   7. any other ≥ Grade 3 laboratory abnormality at baseline (other than those listed above)

   Note: ULN = upper limit of normal. AST = aspartate transaminase, ALT: alanine transaminase, Gamma-GT = Gamma-glutamyl transferase, Alk-P = alkaline phosphatase

5. Requirement for ongoing systemic steroid, or immunosuppressive agents
6. Uncontrolled nausea or vomiting or any symptom that would prevent the ability to comply with daily oral LEAC-102 treatment
7. Active clinically serious infection
8. Known history of HIV or hepatitis B or C Note: HIV = human immunodeficiency virus
9. Uncontrolled psychiatric disorder or altered mental status precluding informed consent or necessary testing
10. Consumption of herbal preparations/supplements (except for a daily multivitamin/mineral supplement not containing herbal components) within 2 weeks prior to the start of Cycle 1 of FOLFOX + Bevacizumab/Cetuximab administration

11. Significant cardiovascular disease, including:

    1. Active clinically symptomatic left ventricular failure
    2. Active hypertension (diastolic blood pressure > 100 mmHg). Subjects with a history of hypertension must have been on stable doses of anti-hypertensive drugs for ≥ 4 weeks prior to start of Cycle 1 of FOLFOX + Bevacizumab/Cetuximab administration
    3. Uncontrolled hypertension: Blood pressure >140/90 mmHg on more than 2 antihypertensive medications
    4. Myocardial infarction, severe angina, or unstable angina within 12 weeks prior to start of Cycle 1 of FOLFOX + Bevacizumab/Cetuximab administration
    5. History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation)
12. Significant gastrointestinal disorder(s) that would, in the opinion of the Principal Investigator, prevent absorption of an orally available agent
13. Has received an investigational agent within 4 weeks of entering this study
14. With any condition judged by the investigator that entering the trial may be detrimental to the subject

15 Female with childbearing potential who is lactating or has positive urine pregnancy test at Screening visit

16. Subject with either gender refuses to adopt at least two forms of birth control (at least one of which must be a barrier method) during the study and until 30 days after study treatment.

Note: Acceptable forms include:

1. Established use of oral, injected or implanted hormonal methods of contraception.
2. Placement of an intrauterine device (IUD) or intrauterine system (IUS).
3. Barrier methods of contraception: Condom OR Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository

17. Subjects with grade 2 or above chronic neuropathy

18. Subjects with known dihydropyrimidine dehydrogenase (DPD) deficiency.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: LEAC-102 and FOLFOX+Bevacizumab/Cetuximab; The subjects will be administered folinic acid (Leucovorin; LV), Fluorouracil (5-FU) and Oxaliplatin (FOLFOX) + Bevacizumab/Cetuximab by intravenous infusion. Cycles repeat every 2 weeks. Dose and schedule modifications may be made at the treating physician's discretion. A standard 3+3 trial design will be used for LEAC-102 dose escalation cohorts.The dosing of LEAC-102 will be divided into 3 cohorts, the subjects will receive LEAC-102 every day Cohort 1: LEAC-102 500 mg capsule, 3 capsules, three times per day for 24 weeks (oral), Cohort 2: LEAC-102 500 mg capsule, 4 capsules, three times per day for 24 weeks (oral), Cohort 3: LEAC-102 500 mg capsule, 5 capsules, three times per day for 24 weeks (oral)

Drug: LEAC-102 500mg capsule and FOLFOX + Bevacizumab/Cetuximab; The subjects will be administered FOLFOX + Bevacizumab/Cetuximab by intravenous infusion. Cycles repeat every 2 weeks. Dose and schedule modifications may be made at the treating physician's discretion. A standard 3+3 trial design will be used for LEAC-102 dose escalation cohorts.The dosing of LEAC-102 will be divided into 3 cohorts, the subjects will receive LEAC-102 every day Cohort 1: LEAC-102 500 mg capsule, 3 capsules, three times per day for 24 weeks (oral), Cohort 2: LEAC-102 500 mg capsule, 4 capsules, three times per day for 24 weeks (oral), Cohort 3: LEAC-102 500 mg capsule, 5 capsules, three times per day for 24 weeks (oral)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum tolerated dose	First two cycles of FOLFOX + Bevacizumab/Cetuximab for advanced Colorectal Cancer (cycle length = 2 weeks)	Week 4

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of adverse events (AEs)	Weeks 0, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22,24
Incidence of serious adverse events (SAEs)	Weeks 0, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22,24
Response rate	Week 24
Progression free survival	Week 24
Overall survival	Week 24
Incidences of myelosuppression	Weeks Weeks 0, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22,24
Change in white blood cells (WBCs) level at all post-treatment visits compared to baseline	Weeks 0, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22,24
Change in platelet level at all post-treatment visits compared to baseline	Weeks 0, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22,24
Change in hemoglobin level at all post-treatment visits compared to baseline	Weeks 0, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22,24
Change in serum inflammatory cytokines level at all post-treatment visits compared to baseline	Weeks 0, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22,24
Change in serum c-reactive protein level at all post-treatment visits compared to baseline	Weeks 0, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22,24
Changes in global health/QoL standardized score at post-treatment visits compared to baseline	Weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22,24

Collaborators and Investigators

• Sponsor: Taiwan Leader Biotech Corp.

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2022
• Primary Completion (Anticipated): February 1, 2024
• Study Completion (Anticipated): February 1, 2024

Study Registration Dates

• First Submitted: June 7, 2016
• First Submitted That Met QC Criteria: July 5, 2016
• First Posted (Estimate): July 11, 2016

Study Record Updates

• Last Update Posted (Actual): October 6, 2021
• Last Update Submitted That Met QC Criteria: September 28, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Advanced Colorectal Cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab; Cetuximab
• Other Study ID Numbers: LEAC-102-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No