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

Metastatic Renal Cell Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02089334
• Other study ID #: RX-0201-P2-A-09
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: August 2014
• Est. completion date: May 17, 2018

Study information

• Verified date: June 2020
• Source: Rexahn Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Terminated
• Enrollment: 24
• Est. completion date: May 17, 2018
• Est. primary completion date: April 26, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Renal Cell
• Metastatic Renal Cell Cancer

Intervention

Drug:
• RX-0201
RX-0201 will be administered in a dose up to 250mg/m^2/day as a continuous infusion for a cycle of 21 days (14 days infused followed by 7 days off) for up to 8 cycles in Stage 1. In Stage 2, RX-0201 will be administered the dose determined in Stage 1 as a continuous infusion for a cycle of 21 days (14 days infused followed by 7 days off) for up to 8 cycles.

Locations

Country	Name	City	State
United States	Rexahn Site	Albuquerque	New Mexico
United States	Rexahn Site	Bronx	New York
United States	Rexahn Site	Duarte	California
United States	Rexahn Site	New York	New York
United States	Rexahn Site	Salt Lake City	Utah
United States	Rexahn Site	Seattle	Washington
United States	Rexahn Site	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Rexahn Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Biomarker Concentrations in Blood	Exploratory analysis of AKT pathway biomarkers, tumor apoptosis biomarkers and other biomarkers in blood or tumor samples	Baseline and at weeks 6, 12, 18, and 24
Other	RX-0201 Concentration in the Blood (Stage 2 Only)	Exploratory analysis of plasma concentrations of RX-0201 at the end of infusion	After 2 weeks of treatment
Primary	Incidence of Dose-limiting Toxicities (DLTs) (Stage 1)	Incidence of adverse events and clinical laboratory abnormalities defined as dose-limiting toxicities	after 1 cycle (3 weeks) of treatment with RX-0201 and everolimus
Primary	Progression Free Survival (Stage 2)	Median PFS. Progression determined by RECIST v1.1	4 months of treatment with RX-0201 and everolimus
Secondary	Steady State Concentration (Css) of RX-0201 (Stage 1)	Css of RX-0201 at the beginning and end of the 14 day continuous infusion	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
Secondary	Incidence of Adverse Events, Changes in Clinical Laboratory Tests and Vital Signs Over Time (Stage 1 and Stage 2)	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.	up to 24 weeks of treatment with RX-0201 plus everolimus and at least 30 days of safety follow up
Secondary	Best Overall Response as Determined by RECIST v1.1.	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.	Baseline and at weeks 6, 12, 18, and 24