A Randomized Phase 2 Trial of Axitinib and TRC105 Versus Axitinib Alone in Patients With Advanced or Metastatic 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: September 8, 2014
Last verified: May 2014
  Purpose

Phase 1b: 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.

Phase 2: To estimate the PFS of patients with advanced or metastatic RCC by RECIST 1.1 criteria in patients treated with axitinib and TRC105 compared to those treated with axitinib alone, following failure of one prior VEGF TKI


Condition Intervention Phase
Renal Cell Carcinoma
Drug: TRC105 and Axitinib
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase 2 Trial of Axitinib and TRC105 Versus Axitinib Alone (Including a lead-in Phase 1B Dose Escalation Portion) in Patients With Advanced or Metastatic Renal Cell Carcinoma

Resource links provided by NLM:


Further study details as provided by Tracon Pharmaceuticals Inc.:

Primary Outcome Measures:
  • Phase 1b [ Time Frame: 1 Year ] [ Designated as safety issue: Yes ]
    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

  • Phase 2 [ Time Frame: 15 Months ] [ Designated as safety issue: No ]
    To estimate the PFS of patients with advanced or metastatic RCC by RECIST 1.1 criteria in patients treated with axitinib and TRC105 compared to those treated with axitinib alone, following failure of one prior VEGF TKI.


Secondary Outcome Measures:
  • Phase 1b: [ Time Frame: 1 Year ] [ Designated as safety issue: No ]

    To look for preliminary evidence of antitumor activity when TRC105 is added to axitinib, by assessing overall response rate and progression-free survival

    To characterize the pharmacokinetic profile of TRC105 when given with axitinib

    To evaluate TRC105 immunogenicity by measuring human antimurine antibody (HAMA) and human antichimeric antibody (HACA) formation

    To explore the pharmacodynamic changes in circulating angiogenic biomarkers following treatment with TRC105 and axitinib


  • Phase 2 [ Time Frame: 15 Months ] [ Designated as safety issue: No ]
    To estimate overall response rate by RECIST 1.1 and Choi criteria, including duration of response by RECIST 1.1 To estimate the disease control rate (CR + PR + SD) at 12 weeks by RECIST 1.1 and Choi criteria, and to estimate the time to next metastasis To determine the frequency and severity of adverse events as assessed by NCI CTCAE (Version 4.0) To evaluate TRC105 immunogenicity as measured by human anti-murine antibody (HAMA) and human anti-chimeric antibody (HACA) concentrations To explore the effects of TRC105 on circulating angiogenic protein biomarkers


Estimated Enrollment: 168
Study Start Date: March 2013
Estimated Study Completion Date: July 2016
Estimated Primary Completion Date: July 2016 (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 or metastatic renal cell carcinoma with a clear cell component that has progressed by investigator assessment following treatment with one and only one multi-targeted tyrosine kinase inhibitor (TKI) other than axitinib that targets the VEGF receptor (VEGFR) (e.g., sunitinib, pazopanib, sorafenib, tivozanib, cabozantinib). One prior immunotherapy (interleukin-2 or interferon-alpha or immune checkpoint inhibitor or tumor vaccine) and one prior mTOR inhibitor treatment are allowed.
  2. No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission per investigators' clinical judgment.
  3. Measurable disease by RECIST 1.1 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. Adequate organ function as defined by the following criteria:
  8. Willingness and ability to consent for self to participate in study
  9. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures

Exclusion Criteria:

  1. Prior treatment with TRC105 or axitinib or any agent targeting the endoglin pathway (including a fusion protein that binds bone morphogenic protein)
  2. Grade 3 or 4 toxicity related to prior VEGFR TKI that did not resolve to grade 1
  3. Current treatment on another therapeutic clinical trial
  4. Receipt of a small molecule anticancer agent, including an investigational anticancer small molecule, within 14 days of starting study treatment or receipt of a biologic anticancer agent (e.g., antibody) within 28 days of starting study treatment.
  5. Prior radiation therapy within 28 days of starting the study treatment, except radiation therapy for bone metastases or radiosurgery is permitted up to 14 days of starting treatment
  6. No major surgical procedure or significant traumatic injury within 6 weeks prior to study registration, and must have fully recovered from any such procedure; date of surgery (if applicable). Note: the following are not considered to be major procedures and are permitted up to 7 days before therapy initiation: Thoracentesis, paracentesis, port placement, laparoscopy, thorascopy, tube thoracostomy, bronchoscopy, endoscopic ultrasonographic procedures, mediastinoscopy, skin biopsies, incisional biopsies, imaging-guided biopsy for diagnostic purposes, and routine dental procedures
  7. 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 < 150/90 mm Hg)
  8. 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 28 days.
  9. Angina, MI, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, arterial embolism, pulmonary embolism, PTCA or CABG within the past 6 months. Deep venous thrombosis within 6 months unless the patient is anticoagulated without the use of warfarin for at least 2 weeks. In this situation, low molecular weight heparin is preferred.
  10. Active bleeding or pathologic condition that carries a high risk of bleeding (e.g. hereditary hemorrhagic telangiectasia).
  11. Thrombolytic use (except to maintain i.v. catheters) within 10 days prior to first day of study therapy
  12. Known active viral or nonviral hepatitis or cirrhosis
  13. History of hemorrhage or hemoptysis (> ½ teaspoon bright red blood) within 3 months of starting study treatment
  14. History of peptic ulcer disease within 3 months of treatment, unless treated for the condition and complete resolution has been documented by esophagogastroduodenoscopy (EGD) within 28 days of starting study treatment
  15. History of gastrointestinal perforation or fistula in the past 6 months, or while previously on antiangiogenic therapy, unless underlying risk has been resolved (e.g., through surgical resection or repair)
  16. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness
  17. Requirement for concomitant medications that strongly induce or inhibit CYP3A4/5
  18. 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. All female patients of reproductive potential must have a negative pregnancy test (serum or urine) within 7 days prior to first dose. Male patients must be surgically sterile or must agree to use effective contraception during the study and for 3 months following last dose of TRC105. The definition of effective contraception will be based on the judgment of the Principal Investigator or a designated associate.
  19. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for this study
  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: Dayle R Craig, RN    205-975-8080    dc0350@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
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02215
Sub-Investigator: David McDermott, MD         
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Meghara Walsh       MWALSH10@PARTNERS.ORG   
Principal Investigator: Toni K. Choueiri, MD         
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Carol Gurski       cgurski@partners.org   
Sub-Investigator: M. Dror Michaelson, 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: September 8, 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
Adenocarcinoma
Kidney Diseases
Kidney Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Urogenital Neoplasms
Urologic Diseases
Urologic Neoplasms
Axitinib
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on October 20, 2014