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

Primary Purpose

Metastatic Renal Cell Cancer

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
RX-0201
Sponsored by
Rexahn Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Renal Cell Cancer focused on measuring renal cell carcinoma, clear cell, renal cancer, metastatic renal cancer, Carcinoma, Renal Cell*/therapy, Humans, Kidney Neoplasms*/therapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Rexahn Site
  • Rexahn Site
  • Rexahn Site
  • Rexahn Site
  • Rexahn Site
  • Rexahn Site
  • Rexahn Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

RX-0201 plus everolimus (Stage 1 & 2)

Arm Description

RX-0201 and everolimus will be taken together as described in the Interventions description.

Outcomes

Primary Outcome Measures

Incidence of Dose-limiting Toxicities (DLTs) (Stage 1)
Incidence of adverse events and clinical laboratory abnormalities defined as dose-limiting toxicities
Progression Free Survival (Stage 2)
Median PFS. Progression determined by RECIST v1.1

Secondary Outcome Measures

Steady State Concentration (Css) of RX-0201 (Stage 1)
Css of RX-0201 at the beginning and end of the 14 day continuous infusion
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.
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.

Full Information

First Posted
March 13, 2014
Last Updated
June 15, 2020
Sponsor
Rexahn Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02089334
Brief Title
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

2. Study Status

Record Verification Date
June 2020
Overall Recruitment Status
Terminated
Study Start Date
August 2014 (Actual)
Primary Completion Date
April 26, 2018 (Actual)
Study Completion Date
May 17, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Rexahn Pharmaceuticals, Inc.

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Renal Cell Cancer
Keywords
renal cell carcinoma, clear cell, renal cancer, metastatic renal cancer, Carcinoma, Renal Cell*/therapy, Humans, Kidney Neoplasms*/therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
24 (Actual)

8. Arms, Groups, and Interventions

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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ely Benaim, MD
Organizational Affiliation
Rexahn Pharmaceuticals, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Rexahn Site
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85719
Country
United States
Facility Name
Rexahn Site
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
Rexahn Site
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87106
Country
United States
Facility Name
Rexahn Site
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
Rexahn Site
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Rexahn Site
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Facility Name
Rexahn Site
City
Seattle
State/Province
Washington
ZIP/Postal Code
98101
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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