Safety and Pharmacokinetic Study of CVM-1118 Extended-Release in Advanced Cancer Patients

NCT04336124 | Completed Phase 1 FDA Drug

• 1 other identifier: CVMEX-001
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 2

Brief Summary

CVM-1118 Immediate-release (IR) Capsule and CVM-1118 Extended-release (ER) Capsule are proprietary oncology products developed by TaiRx, Inc. for the treatment of patients suffering from advanced cancer. Due to the short elimination half-life of CVM-1118 IR capsules, the extended release (ER) formulation, containing mini-tablets in hard capsule, has been developed to prolong the drug absorption and longer exposure after oral administration. The designed dose of CVM-1118 ER was 200 mg per capsule to provide a more patient-compliant and safe dosage of CVM-1118. The clinical study CVMEX-001 is therefore designed to evaluate the safety and pharmacokinetics of CVM-1118 extend release (ER) Capsule (200 mg/capsule) in patients with advanced cancer.

Conditions

Advanced Cancer

Keywords

Oncology; Advanced Solid Malignancy; Tumor Response; Safety and pharmacokinetics

Outcome Measures

Primary Outcomes (2)

• Dose limiting toxicity (DLT) of CVM-1118 ER Capsule

  Dose escalation will occur until DLT occurs in 2 or more patients within a dose level. In any cohort, if 1 patient experiences a DLT, 3 additional patients will be enrolled to that dose level. If 2 or more patients experience a DLT, no further dose escalation will occur.

  up to 28 days

• Maximum tolerated dose (MTD) of CVM-1118 ER Capsule

  The MTD will be defined as the dose level at which at most one of six patients experiences a DLT after 28 days of treatment have occurred, with the next higher dose having at least 2/3 or 2/6 patients experiencing a DLT. The Safety Committee may expand the cohort beyond six patients to better define the safety profile of this cohort in the search for the MTD.

  up to 28 days

Secondary Outcomes (6)

• Preliminary assessment of anti-tumor activity of CVM-1118 ER Capsule

  up to 56 days

• Measure of plasma pharmacokinetic (PK) profiles of CVM-1118 and its metabolite CVM-1125 to include AUC(0-last)

  Cycle 1 Day 1 and Day 15: pre-dose, 2, 3.5, 5, 7, 9, and 12 hours post dose

• Measure of plasma pharmacokinetic (PK) profiles of CVM-1118 and its metabolite CVM-1125 to include Cmax

  Cycle 1 Day 1 and Day 15: pre-dose, 2, 3.5, 5, 7, 9, and 12 hours post dose

• Measure of plasma pharmacokinetic (PK) profiles of CVM-1118 and its metabolite CVM-1125 to include Tmax

  Cycle 1 Day 1 and Day 15: pre-dose, 2, 3.5, 5, 7, 9, and 12 hours post dose

• Measure of plasma pharmacokinetic (PK) profiles of CVM-1118 and its metabolite CVM-1125 to include T(1/2)

  Cycle 1 Day 1 and Day 15: pre-dose, 2, 3.5, 5, 7, 9, and 12 hours post dose

Study Arms (1)

CVM-1118 ER

EXPERIMENTAL

Dose escalation (escalation from 400, 600, 800 to 1200 mg of CVM-1118 ER Capsule)

Drug: CVM-1118 Extended-Release (ER) Capsules (200 mg/capsule)

Interventions

CVM-1118 Extended-Release (ER) Capsules (200 mg/capsule) DRUG

Patients will receive initial dose regimen: 400 mg of CVM-1118 ER Capsule per day (200 mg BID) in a 28-day cycle for 4 cycles. Dose escalates from 400, 600, 800, to 1200 mg of CVM-1118 ER capsules with either BID or TID dosing. A single-patient cohort per dose level (accelerated titration design) will be applied to the first two cohorts, 400 and 600 mg daily, and followed by the conventional 3+3 dose escalation design from the dose level of 800 mg/day. If 2 or more patients experience a DLT, no further dose escalation will occur.

Also known as: TRX-818 ER

CVM-1118 ER

Eligibility Criteria

• Age: 20 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Tumor eligibility:
• Histologically or cytologically confirmed advanced malignancies, which is refractory to standard of care therapy, or for whom no standard of care therapy is available.
• Solid tumors must have measurable or evaluable disease as per Response Evaluation Criteria in Solid Tumors (RECIST v. 1.1). Target lesions that have been previously irradiated will not be considered measurable (lesion) unless increase in size is observed following completion of radiation therapy. Lymphomas must have measurable disease as per Revised Response Criteria for Malignant Lymphomas.
• ECOG performance status 0 to 2. Resolution of all acute toxic effects of prior therapy or surgical procedures to grade 1 (except alopecia).
• Adequate organ function as defined by the following criteria:
• Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) ≤3 x upper limit of normal (ULN), or AST and ALT ≤5 x ULN if liver function abnormalities are due to underlying malignancy
• Total serum bilirubin ≤1.5 x ULN (except for patients with documented Gilbert's syndrome)
• Absolute neutrophil count (ANC) 1,500/µL
• Platelets 90,000/µL
• Hemoglobin 9.0 g/dL
• Serum creatinine ≤1.5 x ULN or creatinine clearance of ≥ 60 mL/min
• Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all the pertinent aspects of the study prior to enrollment.
• Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.

You may not qualify if:

• Patients presenting with any of the following will not be included in the study:
• Major surgery, radiation therapy, or systemic anti-cancer therapy within 4 weeks of starting study treatment.
• Prior high-dose chemotherapy requiring hematopoietic stem cell rescue except for patients with lymphoma
• Current treatment on another clinical study.
• Brain metastases, spinal cord compression, carcinomatous meningitis, or leptomeningeal disease unless appropriately treated and neurologically stable for at least 4 weeks.
• Any of the following within 12 months prior to starting study treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure, or cerebrovascular accident including transient ischemic attack; within 6 months prior to starting study treatment for pulmonary embolus. However, upon agreement between the investigator and sponsor, the 6-month post-event-free period for a patient with a pulmonary embolus can be waived if due to advanced cancers. Appropriate treatment with anticoagulants is permitted.
• Hypertension that cannot be controlled by medications (\>160/100 mmHg despite optimal medical therapy).
• Current treatment with therapeutic doses of warfarin (low dose warfarin up to 2 mg PO daily is allowed).
• Known human immunodeficiency virus infection.
• Hepatitis B virus (HBV) or hepatitis C virus (HCV) with evidence of chronic active disease or receiving/requiring antiviral therapy.
• History of receiving organ transplantation or immune disorders that require continuous immunosuppressant agent therapy.
• Pregnancy or breastfeeding. Female patients must be surgically sterile or be post-menopausal or must agree to the use of effective contraception during the period of therapy. All female patients with reproductive potential must have a negative pregnancy test (serum or urine) prior to enrollment. Male patients must be surgically sterile or must agree to use effective contraception during the period of therapy. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate.
• Other severe acute or chronic medical or psychiatric conditions or laboratory abnormalities that would impart, in the judgment of the investigator and/or sponsor, excess risk associated with study participation or study drug administration, which would make the patient inappropriate for entry into this study.

Sponsors & Collaborators

• TaiRx, Inc.: lead

Study Sites (2)

China Medical University Hospital

Taichung, Taiwan

Location

National Cheng Kung University Hospital

Tainan, 704, Taiwan

Location

MeSH Terms

Conditions

Neoplasms

Interventions

Capsules

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Study Officials

• Wu-Chou Su, M.D.

  National Cheng Kung University Hospital,Taiwan

  PRINCIPAL INVESTIGATOR

• Li-Yuan Bai, M.D.

  China Medical University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 31, 2020
• First Posted: April 7, 2020
• Study Start: May 25, 2020
• Primary Completion: February 8, 2021
• Study Completion: April 8, 2022
• Last Updated: November 28, 2022

Record last verified: 2022-11

Locations

TW (2)