Study of the Combination of CM082 With Everolimus in Patients With mRCC

Phase 1 Study of the Combination of CM082 With Everolimus in Patients With Metastatic Renal Cell Carcinoma (RCC): Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy

This is a Phase I Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of CM082 in Combination with Everolimus in Chinese Patients With Advanced Renal Cell Carcinoma.

Study Overview

• Status: Unknown
• Conditions: Renal Cell Carcinoma Recurrent
• Intervention / Treatment: Drug: CM082; Drug: Everolimus

Detailed Description

This is a Phase I Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of CM082 in Combination with Everolimus in Chinese Patients With Renal Cell Carcinoma (RCC). After the maximum tolerated dose (MTD) or the optimal biological dose is identified, an expansion cohort of ~10 advanced renal cell carcinoma patients will be enrolled to further characterize the safety and tumor response by CT.

• Study Type: Interventional
• Enrollment (Anticipated): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100142
      • Recruiting
      • Beijing Cancer Hospital
      • Contact: Xinan Sheng, M.D; Phone Number: 010-88196951; Email: doctor_sheng@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of clear cell renal cell carcinoma
• Progressed on at least one standard therapy
• Measurable disease per Recist1.1
• Eastern Cooperative Group (ECOG) Performance Status score of 0 or 1
• Life expectancy of at least 12 weeks
• No abnormal bone marrow function

• Adequate heart, lung, liver, kidney organ system functions, and meet the following requirements:

  • 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 ≤5x the upper limit of normal with liver involvement.
  • Creatinine ≤ 1.5 x ULN
  • Urine protein <1+
  • QTcF < 450 ms
  • LVEF ≥ 50%
• At least 4 weeks after receiving cancer therapy (i.e., chemotherapy, radiation therapy, biologic therapy, hormonal therapy); 3 months after surgery and recovered
• 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:

• Currently receiving anti-cancer treatment
• Other tumors in addition to renal cell carcinoma
• 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) or everolimus
• 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 or everolimus
• Patients with known severe lung disorders such as asthma, chronic obstructive pulmonary disease (COPD)
• Patients who are HIV positive
• Drug or alcohol 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 plus everolimus	Drug: CM082; CM082 tablets taken orally once a day on 28-day cycles; Other Names: X-82; Drug: Everolimus; Everolimus tablets taken orally once a day on 28-day cycles; Other Names: Affinitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Tolerated Dose	To determine the Maximum Tolerated Dose of the Combination in Chinese RCC Patients	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics assessed by area under the plasma concentration versus time curve (AUC) of CM082 and everolimus		12 months
Objective response rate	Objective response rate (ORR)	18 months
Progress free survival	Progress free survival (PFS)	24 months

Collaborators and Investigators

• Sponsor: AnewPharma
• Collaborators: Peking University Cancer Hospital & Institute
• Investigators: Principal Investigator: Xinan Sheng, M.D, Peking University Cancer Hospital & Institute

Study record dates

Study Major Dates

• Study Start: September 1, 2015
• Primary Completion (Anticipated): March 1, 2018
• Study Completion (Anticipated): June 1, 2018

Study Registration Dates

• First Submitted: October 12, 2015
• First Submitted That Met QC Criteria: October 15, 2015
• First Posted (Estimate): October 16, 2015

Study Record Updates

• Last Update Posted (Actual): January 10, 2018
• Last Update Submitted That Met QC Criteria: January 8, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Carcinoma; Physiological Effects of Drugs; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Everolimus
• Other Study ID Numbers: CM082-CA-I-103