Study of TRC105 Combined With Standard-Dose Bevacizumab for Advanced Solid Tumors for Which Bevacizumab is Indicated

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Tracon Pharmaceuticals Inc.
ClinicalTrials.gov Identifier:
NCT01332721
First received: April 7, 2011
Last updated: February 12, 2014
Last verified: February 2014
  Purpose

The purpose of the study is to evaluate safety and tolerability and determine a recommended Phase 2 dose for TRC105 when added to standard dose bevacizumab in patients with advanced solid tumors for which bevacizumab is indicated.


Condition Intervention Phase
Adult Solid Tumor
Drug: TRC105 and Bevacizumab
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: An Open Label Phase 1B Dose-Escalation Study of TRC105 Combined With Standard-Dose Bevacizumab for Advanced Solid Tumors

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 Bevacizumab [ Time Frame: 1.5 years ] [ Designated as safety issue: Yes ]
    Safety and dose limiting toxicity will be assessed by dose cohort.


Secondary Outcome Measures:
  • TRC105 Pharmacokinetic Concentrations [ Time Frame: 1.5 years ] [ Designated as safety issue: No ]
    Plasma TRC105 concentrations will be measured at specified timepoints.

  • Immune Response to TRC105 [ Time Frame: 1.5 years ] [ Designated as safety issue: Yes ]
    HAMA and HACA titers will be measured at specified time-points.

  • Objective Response According to RECIST 1.1 [ Time Frame: 1.5 years ] [ Designated as safety issue: No ]
    The best response according to RECIST 1.1 for each patient with measurable disease and who received at least one dose of study drug will be listed by cohort and tumor type


Enrollment: 38
Study Start Date: April 2011
Study Completion Date: December 2013
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TRC105 and Bevacizumab
Escalating doses of i.v. TRC105 will be administered weekly beginning with 3 mg/kg in combination with 15 mg/kg bevacizumab given every 3 weeks. Patients will receive TRC105 treatment on Days 1, 8, and 15 and bevacizumab treatment on Day 1 of each 21-day cycle.
Drug: TRC105 and Bevacizumab
Escalating doses of i.v. TRC105 will be administered weekly beginning with 3 mg/kg in combination with 15 mg/kg bevacizumab given every 3 weeks. Patients will receive TRC105 treatment on Days 1, 8, and 15 and bevacizumab treatment on Day 1 of each 21-day cycle.
Other Names:
  • Chimeric Antibody (TRC105) to CD105
  • Avastin

Detailed Description:

Bevacizumab is a monoclonal antibody to vascular endothelial growth factor (VEGF) that inhibits angiogenesis and extends survival in patients with a wide variety of solid tumor types. TRC105, a monoclonal antibody to CD105, is a novel angiogenesis inhibitor that complements bevacizumab in preclinical models. Together, these antibodies may result in more effective angiogenesis inhibition and improved clinical efficacy over that seen with bevacizumab alone. The purpose of the study is to evaluate safety and tolerability and determine a recommended Phase 2 dose for TRC105 when added to standard dose bevacizumab in patients with advanced solid tumors for which bevacizumab is indicated.

  Eligibility

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

Inclusion Criteria:

  1. Histologically proven advanced or metastatic solid cancer
  2. Measurable disease, evaluable disease or elevation of a relevant soluble tumor marker (e.g., CEA, PSA, CA125)
  3. Age of 18 years or older
  4. ECOG performance status of 0 or 1
  5. Resolution of all acute AEs resulting from prior cancer therapies to NCI CTCAE Grade ≤ 1 or baseline (except alopecia)
  6. Adequate organ function
  7. Willing and able to consent for self to participate in study

Exclusion Criteria:

  1. Prior treatment with TRC105
  2. Serious dose-limiting toxicity related to prior bevacizumab
  3. Current treatment on another therapeutic clinical trial
  4. Receipt of an investigational agent within 28 days of starting study treatment
  5. Prior surgery (including open biopsy) within 28 days of starting the study treatment
  6. Prior radiation therapy or systemic therapy within 21 days of starting the study treatment
  7. Minor surgical procedures such as fine needle aspirations, Mediport placement or core biopsies within 7 days of study treatment
  8. Uncontrolled chronic hypertension defined as systolic > 140 or diastolic > 90 despite optimal therapy (initiation or adjustment of BP medication prior to study entry allowed provided that the average of 3 BP readings at a visit prior to enrollment is < 140/90 mm Hg)
  9. Symptomatic pericardial or pleural effusions
  10. Uncontrolled peritoneal effusions requiring paracentesis more frequently than every 2 weeks
  11. History of brain involvement with cancer, spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease (except in the expansion cohort at the MTD where brain metastases or primary brain tumors are eligible)
  12. Angina, MI, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, arterial embolism, pulmonary embolism, DVT, PTCA or CABG within the past 6 months
  13. Active bleeding or pathologic condition that carries a high risk of bleeding
  14. Thrombolytic or anticoagulant use (except to maintain i.v. catheters) within 10 days prior to first day of study therapy
  15. Cardiac dysrhythmias of NCI CTCAE Grade ≥ 2 within the last 28 days
  16. Known active viral or nonviral hepatitis
  17. Centrally located non-small cell lung cancer (regardless of histologic sub-type), or non-small cell lung cancer of squamous histology.
  18. History of hemorrhage or hemoptysis (>½ teaspoon bright red blood) within 6 months of starting study treatment
  19. Open wounds or unhealed fractures within 28 days of starting study treatment
  20. History of peptic ulcer disease or erosive gastritis within the past 6 months, unless treated for the condition and complete resolution has been documented by esophagogastroduodenoscopy (EGD) within 28 days of starting study treatment
  21. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness
  22. Pregnancy or breastfeeding
  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: NCT01332721

Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35249
United States, Arizona
Pinnacle Oncology Hematology
Scottsdale, Arizona, United States, 85258
United States, California
UCLA Hematology and Oncology
Santa Monica, California, United States, 90404
United States, Indiana
Indiana University Simon Cancer Center
Indianapolis, Indiana, United States, 46202
Sponsors and Collaborators
Tracon Pharmaceuticals Inc.
Investigators
Study Director: Charles P Theuer, MD Tracon Pharmaceuticals Inc.
  More Information

No publications provided

Responsible Party: Tracon Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT01332721     History of Changes
Other Study ID Numbers: 105ST102
Study First Received: April 7, 2011
Results First Received: February 12, 2014
Last Updated: February 12, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Tracon Pharmaceuticals Inc.:
TRC105
CD105
Endoglin
Solid Tumors
Avastin
Bevacizumab

Additional relevant MeSH terms:
Neoplasms
Bevacizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014