Clinical trial NCT02577458: Study of the Combination of CM082 With Everolimus in Patients With mRCC
Official title: Phase 1 Study of the Combination of CM082 With Everolimus in Patients With Metastatic Renal Cell Carcinoma (RCC): Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Renal Cell Carcinoma Recurrent
Lead sponsor: AnewPharma
Sponsor class: INDUSTRY
Collaborators: name: Peking University Cancer Hospital & Institute
First posted: 2015-10-16
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Maximum Tolerated Dose
timeFrame: 12 months
Secondary outcomes:
measure: Pharmacokinetics assessed by area under the plasma concentration versus time curve (AUC) of CM082 and everolimus
timeFrame: 12 months
measure: Objective response rate
timeFrame: 18 months
measure: Progress free survival
timeFrame: 24 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
Study officials:
affiliation: Peking University Cancer Hospital & Institute
name: Jun Guo, M.D
role: STUDY_CHAIR
affiliation: Peking University Cancer Hospital & Institute
name: Xinan Sheng, M.D
role: PRINCIPAL_INVESTIGATOR
References: