LEAC-102 for Advanced Colorectal Cancer

Phase 1

• Conditions: Advanced Colorectal Cancer
• Interventions: Drug: LEAC-102 500mg capsule and FOLFOX + Bevacizumab/Cetuximab

• Registration Number: NCT02826837
• Lead Sponsor: Taiwan Leader Biotech Corp.

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-06-07
• Study First Submitted QC: 2016-07-05
• Study First Posted: 2016-07-11
• Status Verified: 2021-09
• Last Update Submitted: 2021-09-28
• Last Update Posted: 2021-10-06
• Study Start: 2022-09-01
• Primary Completion: 2024-02-01
• Study Completion: 2024-02-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

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

4. Subjects with grade 2 or above chronic neuropathy

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
LEAC-102 and FOLFOX+Bevacizumab/Cetuximab	LEAC-102 500mg capsule 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)

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Response rate	Week 24
Overall survival	Week 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 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
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 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
Progression free survival	Week 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
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
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