A Phase 1B Dose-escalation Study of TRC105 in Combination With Axitinib in Patients With Advanced Renal Cell Carcinoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Tracon Pharmaceuticals Inc.
Sponsor:
Information provided by (Responsible Party):
Tracon Pharmaceuticals Inc.
ClinicalTrials.gov Identifier:
NCT01806064
First received: February 26, 2013
Last updated: May 5, 2014
Last verified: May 2014
  Purpose

To evaluate safety and tolerability and determine a recommended phase 2 dose for TRC105 when added to standard dose axitinib in patients with advanced renal cell carcinoma.


Condition Intervention Phase
Renal Cell Carcinoma
Drug: TRC105 and Axitinib
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A PHASE 1B DOSE-ESCALTION STUDY OF TRC105 IN COMBINATION WITH AXITINIB IN PATIENTS WITH ADVANCED RENAL CELL CARCINOMA

Resource links provided by NLM:


Further study details as provided by Tracon Pharmaceuticals Inc.:

Primary Outcome Measures:
  • Determine Maximum Tolerated Dose of TRC105 in Combination with Axitinib [ Time Frame: 1 Year ] [ Designated as safety issue: Yes ]
    Safety and dose limiting toxicity will be assessed by dose cohort.


Secondary Outcome Measures:
  • TRC105 Pharmacokinetic Concentrations [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
    Plasma TRC105 concentrations will be measured at specified timepoints.


Estimated Enrollment: 18
Study Start Date: March 2013
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TRC105 and Axitinib Drug: TRC105 and Axitinib
Other Names:
  • Chimeric Antibody (TRC105) to CD105
  • INLYTA

Detailed Description:

Axitinib is an oral inhibitor of multiple receptor tyrosine kinases including vascular endothelial growth factor receptor VEGFR-1, VEGFR-2, and VEGFR-3 at therapeutic plasma concentrations. These receptors are implicated in pathologic angiogenesis, tumor growth, and cancer progression. Axitinib is approved for the treatment of advanced renal cell carcinoma, following progression on one prior systemic therapy. TRC105 is an antibody to CD105, an important angiogenic target on vascular endothelial cells that is distinct from VEGFR. TRC105 inhibits angiogenesis, tumor growth and metastases in preclinical models and complements the activity of bevacizumab and multi-kinase inhibitors that target VEGFR. In a phase 1 study of advanced solid tumors,TRC105 therapy caused a global reduction in angiogenic biomarkers and reduced tumor burden at doses that were well-tolerated. By targeting a non-VEGF pathway that is upregulated following VEGF inhibition, TRC105 has the potential to complement VEGF inhibitors and could represent a major advance in cancer therapy. TRC105 potentiates bevacizumab and VEGFR tyrosine kinases (VEGFR TKI) in preclinical models. In a phase 1b study, the combination of TRC105 and bevacizumab produced radiographic reductions in tumor volume in bevacizumab refractory patients. Together, the use of TRC105 with axitinib may result in more effective angiogenesis inhibition and improved clinical efficacy over that seen with axitinib alone.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologically confirmed advanced renal cell carcinoma that has progressed following treatment with at least one multi-targeted tyrosine kinase inhibitor that targets the VEGF receptor (e.g., sunitinib, pazopanib, sorafenib, tivozanib). Prior immunotherapy, bevacizumab or mTOR inhibitor treatment is allowed. Patients who experienced > grade 3 toxicity on prior VEGF or VEGF receptor treatment are excluded unless the toxicity resolved to grade 1 following medical intervention and continued VEGF or VEGF receptor treatment.
  2. No history of other carcinoma within the last five years, and/or where the risk of recurrence is known to be under 5%
  3. Measurable disease by RECIST criteria
  4. Age of 18 years or older
  5. ECOG performance status ≤ 1
  6. Resolution of all acute adverse events resulting from prior cancer therapies to NCI CTCAE grade ≤ 1 or baseline (except alopecia)
  7. Willingness and ability to consent for self to participate in study

Exclusion Criteria:

  1. Prior treatment with TRC105
  2. Current treatment on another therapeutic clinical trial
  3. Receipt of a small molecule anticancer agent, including an investigational anticancer small molecule, within 14 days of starting study treatment
  4. Receipt of a large molecule anticancer agent (e.g., antibody), including an investigational anticancer antibody, within 28 days of starting study treatment
  5. Prior surgery (including open biopsy) within 28 days of starting the study treatment or the anticipated need for a major surgical procedure within the next six months
  6. Prior radiation therapy within 28 days of starting the study treatment, except radiation therapy for bone metastases is permitted up to 14 days of starting treatment
  7. Minor surgical procedures such as fine needle aspiration, Mediport placement or core biopsy within 7 days of study treatment
  8. Uncontrolled chronic hypertension defined as systolic > 150 or diastolic > 90 despite optimal therapy (initiation or adjustment of BP medication prior to study entry is allowed provided that the average of 3 BP readings at a visit prior to enrollment is < 140/90 mm Hg)
  9. Symptomatic ascites or pericardial or pleural effusion
  10. History of brain involvement with cancer, spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease. Patients with radiated or resected lesions are permitted, provided the lesions are fully treated and inactive, patients are asymptomatic, and no steroids have been administered for at least 30 days.
  11. Angina, MI, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, arterial embolism, pulmonary embolism, Venous thrombosis, including pulmonary embolism and deep venous thrombosis (unless adequately anticoagulated without warfarin for more than two weeks), PTCA or CABG within the past 6 months
  12. Active bleeding or pathologic condition that carries a high risk of bleeding (e.g. hereditary hemorrhagic telangiectasia). Patients who have been uneventfully anti-coagulated with low molecular weight heparin are eligible.
  13. Thrombolytic use (except to maintain i.v. catheters) within 10 days prior to first day of study therapy
  14. Cardiac dysrhythmias of NCI CTCAE grade ≥ 2 within the last 28 days
  15. Known active viral or nonviral hepatitis or cirrhosis
  16. History of hemorrhage or hemoptysis (> ½ teaspoon bright red blood) within 6 months of starting study treatment
  17. Pregnancy or breastfeeding. Female patients must be surgically sterile (i.e.: hysterectomy) or be postmenopausal, or must agree to use effective contraception during the study and for 3 months following last dose of TRC105.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01806064

Contacts
Contact: Manoj Jivani mjivani@traconpharma.com
Contact: Bonne Adams badams@traconpharma.com

Locations
United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35294
Contact: Sharon R Barkley    205-975-2008    sbarkley@uab.edu   
Principal Investigator: Guru P. Sonpavde, MD         
United States, California
Cedars-Sinai Medical Center Recruiting
Los Angeles, California, United States, 90048
Contact: Nancy Moldawer       Nancy.Moldawer@cshs.org   
Principal Investigator: Edwin Posadas, MD         
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Carol Gurski       cgurski@partners.org   
Sub-Investigator: M. Dror Michaelson, MD         
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Meghara Walsh       MWALSH10@PARTNERS.ORG   
Principal Investigator: Toni K. Choueiri, MD         
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02215
Sub-Investigator: David McDermott, MD         
Sponsors and Collaborators
Tracon Pharmaceuticals Inc.
  More Information

No publications provided

Responsible Party: Tracon Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT01806064     History of Changes
Other Study ID Numbers: 105RC101
Study First Received: February 26, 2013
Last Updated: May 5, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Tracon Pharmaceuticals Inc.:
TRC105
CD105
RCC
Renal Cell Carcinoma
Axitinib
INLYTA
Advanced Renal Cell Carcinoma

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Axitinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014