Clinical trial NCT02089334: Dose-Finding, Safety and Efficacy Study of RX-0201 Plus Everolimus in Metastatic Renal Cell Cancer
Official title: A Multicenter, Open-label, Phase 1b/2 Study to Evaluate the Safety and Efficacy of RX-0201 in Combination With Everolimus to Treat Subjects With Advanced Renal Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Metastatic Renal Cell Cancer
Keywords: renal cell carcinoma
clear cell
renal cancer
metastatic renal cancer
Carcinoma, Renal Cell*/therapy
Humans
Kidney Neoplasms*/therapy
Lead sponsor: Rexahn Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2014-03-17
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the maximum tolerated dose of RX-0201, up to a target dose of 250 mg/m\^2/day, when given in combination with everolimus (Stage 1), and to assess the safety and efficacy of RX-0201 plus everolimus, in subjects with metastatic renal cell cancer (Stage 2).

Detailed description: This multi-center, open-label, randomized, parallel group study of RX-0201 in combination with everolimus, versus everolimus alone to treat subjects with advanced renal cell carcinoma will be conducted in 2 stages. Stage 1 will be an open-label, dose-escalation study of RX-0201 to identify a safe and tolerable dose of RX-0201 up to a target dose of 250 mg/m\^2/day when given in combination with everolimus. Stage 2 will be a randomized, open-label, 2-arm study of RX-0201 in combination with everolimus versus everolimus alone. Subjects will receive RX-0201, at the dose identified in Stage 1, in combination with everolimus or everolimus alone, for up to 8 cycles to determine safety and efficacy of the combination.

Eligibility criteria: Inclusion Criteria:

* Males and females ≥ 18 years of age at screening
* Histological or cytological diagnosis of renal cell cancer with a clear-cell component
* Measurable or evaluable disease defined by Response Evaluation Criteria for Solid Tumors (RECIST) ver. 1.1
* Must have received at least one course of therapy with a VEGFR-targeting tyrosine kinase inhibitor (eg, sorafenib, sunitinib, axitinib, pazopanib or tivozanib) and progressed within 6 months of planned first dose of study treatment
* ECOG performance status of 0,1 or 2
* Life expectancy \> 3 months
* Provide written informed consent

Exclusion Criteria:

* Brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery and stable for at least 3 months before planned first dose of study drug
* Radiation therapy for bone metastasis within 2 weeks, any other external radiation therapy within 4 weeks before planned first dose of study drug. Systemic treatment with radionuclides within 6 weeks before planned first dose of study drug. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible
* Prior treatment with everolimus, or any other specific or selective TORC1/PI3K/AKT inhibitor (eg, temsirolimus)
* Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before planned first dose of study drug
* Receipt of any type of anticancer antibody (including investigational antibody) within 4 weeks before planned first dose of study drug
* Taking strong inducers or inhibitors of CYP450s for subjects receiving everolimus
* Chronic treatment with corticosteroids or other immunosuppressive agents
* Concomitant anticoagulation at therapeutic doses with oral anticoagulants or platelet inhibitors
* Subjects with a known hypersensitivity to everolimus or other rapamycins (sirolimus, temsirolimus) or to its excipients
* Major surgery within 2 months before planned first dose of study drug
* Myocardial infarction within the previous 6 months before planned first dose of study drug
* Active infection requiring parenteral antibiotics within 2 weeks before planned first dose of study drug
* Diagnosis of another malignancy within 2 years before planned first dose of study drug, except for superficial skin cancers, or localized, low grade tumors
* Prior or current history of hepatitis B, hepatitis C or human immunodeficiency virus
* Sexually active fertile subjects (male and female) must agree to use medically accepted methods of contraception during the course of the study and for 30 days after the last dose of study treatment

Primary outcomes:
measure: Incidence of Dose-limiting Toxicities (DLTs) (Stage 1)
timeFrame: after 1 cycle (3 weeks) of treatment with RX-0201 and everolimus
measure: Progression Free Survival (Stage 2)
timeFrame: 4 months of treatment with RX-0201 and everolimus
Secondary outcomes:
measure: Steady State Concentration (Css) of RX-0201 (Stage 1)
timeFrame: predose, 1, 2, 3, 4, 6, and 24 hours after start of Cycle 1 RX-0201 infusion, and then immediately prior to the end of Cycle 1 infusion (Day 15), 1, 2, 3, 4, 6, and 24 hours after infusion is stopped
measure: Incidence of Adverse Events, Changes in Clinical Laboratory Tests and Vital Signs Over Time (Stage 1 and Stage 2)
timeFrame: up to 24 weeks of treatment with RX-0201 plus everolimus and at least 30 days of safety follow up
measure: Best Overall Response as Determined by RECIST v1.1.
timeFrame: Baseline and at weeks 6, 12, 18, and 24
Other outcomes:
measure: Biomarker Concentrations in Blood
timeFrame: Baseline and at weeks 6, 12, 18, and 24
measure: RX-0201 Concentration in the Blood (Stage 2 Only)
timeFrame: After 2 weeks of treatment
Locations:
city: Tucson
country: United States
facility: Rexahn Site
state: Arizona
city: Duarte
country: United States
facility: Rexahn Site
state: California
city: Albuquerque
country: United States
facility: Rexahn Site
state: New Mexico
city: Bronx
country: United States
facility: Rexahn Site
state: New York
city: New York
country: United States
facility: Rexahn Site
state: New York
city: Salt Lake City
country: United States
facility: Rexahn Site
state: Utah
city: Seattle
country: United States
facility: Rexahn Site
state: Washington
Study officials:
affiliation: Rexahn Pharmaceuticals, Inc.
name: Ely Benaim, MD
role: STUDY_DIRECTOR
References: