Phase 1 Study of CM082 (X-82) Tablets in Advanced Cancer Patients in China

Phase 1 Safety, Tolerability, and Pharmacokinetic Study of CM082 (X-82) Tablets in Advanced Cancer Patients in China

This is a Phase I Dose-Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of CM082 tablets in Chinese Patients With Advanced Solid Tumors.

Study Overview

• Status: Completed
• Conditions: Advanced Cancer
• Intervention / Treatment: Drug: CM082 Tablet

Detailed Description

This is a Phase I Dose-Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of CM082 tablets in Chinese Patients With Advanced Solid Tumors. After the maximum tolerated dose (MTD) or the optimal biological dose is identified, an expansion cohort of ~20 advanced renal cell carcinoma patients will be enrolled to further characterize the safety and tumor response by CT.

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100021
    • Cancer Institute and Hospital, Chinese Academy of Medical Sciences
  • Beijing
    • Beijing, Beijing, China, 100034
      • Beijing University First Hospital
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Tianjin Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of advanced solid tumor malignancy that is not responsive to standard therapies or for which there is no effective therapy.
• Eastern Cooperative Group (ECOG) Performance Status score of 0 or 1.
• Life expectancy of at least 12 weeks.
• No immuno deficiency.

• Adequate organ system function, defined as follows:

  • Absolute neutrophil count (ANC) ≥1.5 x 10**9/L
  • Platelets ≥100 x 10**9/L
  • Hemoglobin ≥10 g/dL
  • Total bilirubin ≤1.5 times the upper limit of normal (ULN)
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤1.5x the upper limit of normal (ULN) if no liver involvement or ≤2.5x the upper limit of normal with liver involvement.
  • Creatinine ≤ 1.5 x ULN.
• At least 4 weeks or 5 half-life after receiving cancer therapy (i.e., chemotherapy, radiation therapy, immunotherapy, biologic therapy, hormonal therapy, surgery and/or tumor embolization.
• Willingness and ability to comply with trial and follow-up procedures.
• Ability to understand the nature of this trial and give written informed consent.

Exclusion Criteria:

• Not recovered from prior anti-cancer therapy or surgery.
• Have taken strong cytochrome P450 3A4 inhibitors or inducers in the last 2 weeks.
• Concomitant use of drugs with a risk of causing prolonged corrected QT interval and/or Torsades de Pointes.
• Patients with a history of intolerance to, or significant toxicity with, VEGFR tyrosine kinase inhibitor(s) (TKI).
• Females who are pregnant or breastfeeding.
• Those in reproductive ages who refuse to use contraception.
• Those with concurrent condition(e.g. psychological, neuronal, cardiovascular, respiratory conditions or infections) that in the investigator's opinion would jeopardize compliance with the protocol.
• Patients with known central nervous system (CNS) metastases.
• Presence of active gastrointestinal (GI) disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of CM082 (X-82).
• Patients with known GI disorders such as vomiting, diarrhea.
• Patients who are hepatitis B virus positive.
• Drug abuser.

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: CM082; CM082 tablet	Drug: CM082 Tablet; CM082 tablets taken orally once a day on 28-day cycles; Other Names: X-82

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Tolerated Dose	To determine the Maximum Tolerated Dose in Chinese patients with advanced solid tumors.	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Preliminary biological activity	clinical tumor response by computed tomography (CT) after treatment with CM082 tablets given as a single agent.	24 months
Area Under Curve		2 months
Half-life time		2 months
Cmax	Peak concentration	2 months
Tmax	Time to Cmax	2 months

Collaborators and Investigators

• Sponsor: AnewPharma
• Collaborators: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
• Investigators: Principal Investigator: Jin-Wan Wang, M.D., Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing

Study record dates

Study Major Dates

• Study Start: May 1, 2013
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): May 1, 2016

Study Registration Dates

• First Submitted: May 22, 2013
• First Submitted That Met QC Criteria: May 23, 2013
• First Posted (Estimate): May 29, 2013

Study Record Updates

• Last Update Posted (Actual): July 5, 2019
• Last Update Submitted That Met QC Criteria: July 2, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: advanced cancer
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Vorolanib
• Other Study ID Numbers: CM082-CA-I-001; 2013L00579、2013L00581 (Other Identifier: China FDA)