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

June 15, 2020 updated by: Rexahn Pharmaceuticals, Inc.

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

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).

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

24

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Tucson, Arizona, United States, 85719
        • Rexahn Site
    • California
      • Duarte, California, United States, 91010
        • Rexahn Site
    • New Mexico
      • Albuquerque, New Mexico, United States, 87106
        • Rexahn Site
    • New York
      • Bronx, New York, United States, 10467
        • Rexahn Site
      • New York, New York, United States, 10065
        • Rexahn Site
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Rexahn Site
    • Washington
      • Seattle, Washington, United States, 98101
        • Rexahn Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: RX-0201 plus everolimus (Stage 1 & 2)
RX-0201 and everolimus will be taken together as described in the Interventions description.
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.

Other Names:
  • Archexin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Dose-limiting Toxicities (DLTs) (Stage 1)
Time Frame: 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
after 1 cycle (3 weeks) of treatment with RX-0201 and everolimus
Progression Free Survival (Stage 2)
Time Frame: 4 months of treatment with RX-0201 and everolimus
Median PFS. Progression determined by RECIST v1.1
4 months of treatment with RX-0201 and everolimus

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Steady State Concentration (Css) of RX-0201 (Stage 1)
Time Frame: 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
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
Incidence of Adverse Events, Changes in Clinical Laboratory Tests and Vital Signs Over Time (Stage 1 and Stage 2)
Time Frame: 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.
up to 24 weeks of treatment with RX-0201 plus everolimus and at least 30 days of safety follow up
Best Overall Response as Determined by RECIST v1.1.
Time Frame: 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.
Baseline and at weeks 6, 12, 18, and 24

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Biomarker Concentrations in Blood
Time Frame: Baseline and at weeks 6, 12, 18, and 24
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
RX-0201 Concentration in the Blood (Stage 2 Only)
Time Frame: After 2 weeks of treatment
Exploratory analysis of plasma concentrations of RX-0201 at the end of infusion
After 2 weeks of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Rexahn Pharmaceuticals, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

August 1, 2014

Primary Completion (ACTUAL)

April 26, 2018

Study Completion (ACTUAL)

May 17, 2018

Study Registration Dates

First Submitted

March 13, 2014

First Submitted That Met QC Criteria

March 13, 2014

First Posted (ESTIMATE)

March 17, 2014

Study Record Updates

Last Update Posted (ACTUAL)

June 30, 2020

Last Update Submitted That Met QC Criteria

June 15, 2020

Last Verified

June 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RX-0201-P2-A-09

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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