Open Label Dose-Finding Study of TRC105 Plus Capecitabine for Metastatic Breast Cancer (TRC105)

An Open Label Phase 1B Dose-Finding Study of TRC105 in Combination With Capecitabine for Progressive or Recurrent Metastatic Breast Cancer

The purpose of this study is to determine the recommended phase 2 dose and overall safety and tolerability of TRC105 when given in combination with capecitabine for the treatment of patients with progressive or recurrent metastatic breast cancer.

Study Overview

• Status: Completed
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Drug: Capecitabine; Drug: TRC105

Detailed Description

All patients were required to sign a consent form prior to undertaking any study-related procedures. Prospective patients were screened to determine if they qualified for the study within 28 days of enrollment. Patients who qualified received TRC105 i.v. over 1 to 4 hours on Day 1, Day 4, Day 8 and Day 15 of the initial 21-day cycle and Day 1, Day 8 and Day 15 of every subsequent 21-day cycle in combination with 1000 mg/m2 capecitabine BID for 14 days of each 21-day cycle. Those who tolerated TRC105 without any infusion reactions were eligible for reduced infusion durations. After 3 cycles of treatment, patients who demonstrated a response of complete response (CR), partial response (PR) or stable disease (SD) were eligible for additional treatment for up to six months (9 total cycles). Upon discussion with TRACON, patients judged by the Principal Investigator to be benefiting from treatment were able to continue treatment on this protocol beyond six months.

Toxicities were graded according to the NCI CTCAE Version 4.0. Patients who exited the study for reasons other than drug-related toxicity prior to completion of the first 21-day cycle were replaced. Intra-patient dose escalation was not allowed.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-3300
      • University of Alabama at Birmingham
  • New York
    • Buffalo, New York, United States, 14201
      • Roswell Park Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically proven advanced solid cancer for which curative therapy is not available (Part 1 only)
• Histologically proven metastatic Her-2-negative breast cancer (Part 2 only)
• Measurable disease by RECIST 1.1 criteria (Part 2 only)
• Willing and able to consent for self to participate in study
• Progressive or recurrent disease after prior systemic chemotherapy regimen
• Age ≥ 18 years
• ECOG performance status of 0 or 1
• Resolution of all acute toxic effects of prior therapy to NCI CTCAE Grade ≤ 1 or baseline (except alopecia)
• Adequate organ function

Exclusion Criteria:

• Prior treatment with more than one systemic chemotherapy regimen for metastatic disease.
• Prior treatment with TRC105
• History of hypersensitivity reaction to antimetabolite therapy
• Receipt of an investigational agent within 28 days of starting study treatment
• Prior surgery (including open biopsy), radiation therapy or systemic therapy within 28 days of starting study treatment
• Minor surgical procedures within 14 days prior to first dose of TRC105
• History of brain metastasis, spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease
• Angina, MI, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, arterial embolism, pulmonary embolism, DVT, PTCA or CABG within the past 6 months
• Uncontrolled chronic hypertension defined as systolic > 140 or diastolic > 90 despite optimal therapy
• Past medical history of acquired or inherited coagulopathy including patients with known hereditary hemorrhagic telangiectasia
• Thrombolytic or anticoagulant use (except to maintain i.v. catheters) within 10 days prior to first dose with TRC105
• Cardiac dysrhythmias of NCI CTCAE Grade ≥ 2 within the last month
• Hemorrhage within 28 days of starting study treatment
• Unhealed wounds within 28 days of starting study treatment
• History of peptic ulcer disease or 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
• Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness
• Known active viral or nonviral hepatitis
• History of hypersensitivity reaction to human or mouse antibody products
• Lung cancer with central chest lesions
• Pregnancy or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single; All patients received TRC105 + capecitabine	Drug: Capecitabine; oral; Other Names: xeloda; Drug: TRC105; IV; Other Names: carotuximab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine Maximum Tolerated Dose of TRC105 in Combination With Capecitabine	Assess safety and dose limiting toxicity by dose cohort and coding all terms utilized MedDRA version 14.1.	1.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TRC105 Steady State Pharmacokinetic Trough Concentration at the RP2D	Mean trough concentration for patients dosed at 10 mg/kg at cycle 2 day 1	Cycle 2 day 1 (3 weeks)
Number of Patients With Positive Immune Response to TRC105	Serial blood samples will be tested for anti-drug antibody (ADA) immune response to TRC105. Patients who are positive at baseline (prior to receiving TRC105) are excluded from analysis.	1.5 years
Number of Patients With Objective Response According to RECIST 1.1	The best response according to RECIST 1.1 for each patient with measurable disease who received at least one dose of study drug will be listed by cohort and tumor type	1.5 years

Collaborators and Investigators

• Sponsor: Tracon Pharmaceuticals Inc.
• Collaborators: United States Department of Defense; Roswell Park Cancer Institute
• Investigators: Study Chair: Charles Theuer, MD PhD, Tracon Pharmaceuticals Inc.

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Actual): September 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: March 25, 2011
• First Submitted That Met QC Criteria: March 29, 2011
• First Posted (Estimate): March 31, 2011

Study Record Updates

• Last Update Posted (Actual): March 18, 2019
• Last Update Submitted That Met QC Criteria: February 28, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: Breast Cancer; Endoglin; Department of Defense; TRC105; CD105; TRACON Pharma; Roswell Park Cancer Institute
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Capecitabine
• Other Study ID Numbers: 105BC102