Dose-Finding, Safety and Efficacy Study of RX-0201 Plus Everolimus in Metastatic Renal Cell Cancer

Phase 1

Terminated

Conditions: Metastatic Renal Cell Cancer

Interventions: Drug: RX-0201

Registration Number: NCT02089334

Lead Sponsor: Rexahn Pharmaceuticals, Inc.

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 24

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
RX-0201 plus everolimus (Stage 1 & 2)	RX-0201	RX-0201 and everolimus will be taken together as described in the Interventions description.

Primary Outcome Measures

Name	Time	Method
Incidence of Dose-limiting Toxicities (DLTs) (Stage 1)	after 1 cycle (3 weeks) of treatment with RX-0201 and everolimus	Incidence of adverse events and clinical laboratory abnormalities defined as dose-limiting toxicities
Progression Free Survival (Stage 2)	4 months of treatment with RX-0201 and everolimus	Median PFS. Progression determined by RECIST v1.1

Secondary Outcome Measures

Name	Time	Method
Incidence of Adverse Events, Changes in Clinical Laboratory Tests and Vital Signs Over Time (Stage 1 and Stage 2)	up to 24 weeks of treatment with RX-0201 plus everolimus and at least 30 days of safety follow up	safety of RX-0201 was evaluated through reporting using the grading system in the CTCAE version 4.03 for adverse events and laboratory abnormalities. All statistical methods for safety were descriptive in nature.
Steady State Concentration (Css) of RX-0201 (Stage 1)	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	Css of RX-0201 at the beginning and end of the 14 day continuous infusion
Best Overall Response as Determined by RECIST v1.1.	Baseline and at weeks 6, 12, 18, and 24	Best overall response as determined by RECIST v1.1. Not Evaluable included the subjects who had completed at least one treatment cycle but no overall response evaluation. Not Done included the subjects who dropped out from the study without completing any treatment cycle and overall response evaluation. The best overall response for each subject from all post-baseline time point overall responses was used. The best overall response was the best response recorded from the start of the treatment until disease progression/recurrence, or occurrence of intolerable toxicity, whatever came first.