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

NCT02089334 | Terminated Phase 1 Results

• 1 other identifier: RX-0201-P2-A-09
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 7

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).

Conditions

Metastatic Renal Cell Cancer

Keywords

renal cell carcinoma; clear cell; renal cancer; metastatic renal cancer; Carcinoma, Renal Cell*/therapy; Humans; Kidney Neoplasms*/therapy

Outcome Measures

Primary Outcomes (2)

• 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

• Progression Free Survival (Stage 2)

  Median PFS. Progression determined by RECIST v1.1

  4 months of treatment with RX-0201 and everolimus

Secondary Outcomes (3)

• 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

• 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

• Best Overall Response as Determined by RECIST v1.1.

  Baseline and at weeks 6, 12, 18, and 24

Other Outcomes (2)

• Biomarker Concentrations in Blood

  Baseline and at weeks 6, 12, 18, and 24

• RX-0201 Concentration in the Blood (Stage 2 Only)

  After 2 weeks of treatment

Study Arms (1)

RX-0201 plus everolimus (Stage 1 & 2)

EXPERIMENTAL

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

Drug: RX-0201

Interventions

RX-0201 DRUG

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.

Also known as: Archexin

RX-0201 plus everolimus (Stage 1 & 2)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Rexahn Pharmaceuticals, Inc.: lead

Study Sites (7)

Rexahn Site

Tucson, Arizona, 85719, United States

Location

Rexahn Site

Duarte, California, 91010, United States

Location

Rexahn Site

Albuquerque, New Mexico, 87106, United States

Location

Rexahn Site

New York, New York, 10065, United States

Location

Rexahn Site

The Bronx, New York, 10467, United States

Location

Rexahn Site

Salt Lake City, Utah, 84112, United States

Location

Rexahn Site

Seattle, Washington, 98101, United States

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell; Kidney Neoplasms; Carcinoma

Interventions

RX-0201

Condition Hierarchy (Ancestors)

Adenocarcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Limitations and Caveats

Early termination lead to small numbers of subjects analyzed. Missing samples and technical problems with the bioanalysis resulted in uninterpretable PK data.

Results Point of Contact

• Title: Doug Swirsky/ Chief Executive Officer
• Organization: Rexahn Pharmaceuticals Inc.

swirskyd@rexahn.com

240-268-5300

Study Officials

• Ely Benaim, MD

  Rexahn Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2014
• First Posted: March 17, 2014
• Study Start: August 1, 2014
• Primary Completion: April 26, 2018
• Study Completion: May 17, 2018
• Last Updated: June 30, 2020
• Results First Posted: June 30, 2020

Record last verified: 2020-06

Locations

US (7)