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

Sponsor
Tracon Pharmaceuticals Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT01326481
Collaborator
Roswell Park Cancer Institute (Other), United States Department of Defense (U.S. Fed)
19
2
1
42
9.5
0.2

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

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 Design

Study Type:
Interventional
Actual Enrollment :
19 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open Label Phase 1B Dose-Finding Study of TRC105 in Combination With Capecitabine for Progressive or Recurrent Metastatic Breast Cancer
Study Start Date :
Jun 1, 2011
Actual Primary Completion Date :
Sep 1, 2014
Actual Study Completion Date :
Dec 1, 2014

Arms and Interventions

Arm Intervention/Treatment
Experimental: Single

All patients received TRC105 + capecitabine

Drug: TRC105
IV
Other Names:
  • carotuximab
  • Drug: Capecitabine
    oral
    Other Names:
  • xeloda
  • Outcome Measures

    Primary Outcome Measures

    1. Determine Maximum Tolerated Dose of TRC105 in Combination With Capecitabine [1.5 years]

      Assess safety and dose limiting toxicity by dose cohort and coding all terms utilized MedDRA version 14.1.

    Secondary Outcome Measures

    1. TRC105 Steady State Pharmacokinetic Trough Concentration at the RP2D [Cycle 2 day 1 (3 weeks)]

      Mean trough concentration for patients dosed at 10 mg/kg at cycle 2 day 1

    2. Number of Patients With Positive Immune Response to TRC105 [1.5 years]

      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.

    3. Number of Patients With Objective Response According to RECIST 1.1 [1.5 years]

      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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 120 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Alabama at Birmingham Birmingham Alabama United States 35294-3300
    2 Roswell Park Cancer Institute Buffalo New York United States 14201

    Sponsors and Collaborators

    • Tracon Pharmaceuticals Inc.
    • Roswell Park Cancer Institute
    • United States Department of Defense

    Investigators

    • Study Chair: Charles Theuer, MD PhD, Tracon Pharmaceuticals Inc.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Tracon Pharmaceuticals Inc.
    ClinicalTrials.gov Identifier:
    NCT01326481
    Other Study ID Numbers:
    • 105BC102
    First Posted:
    Mar 31, 2011
    Last Update Posted:
    Mar 18, 2019
    Last Verified:
    Feb 1, 2019
    Keywords provided by Tracon Pharmaceuticals Inc.
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Carotuximab (TRC105) Plus Capecitabine
    Arm/Group Description All patients received TRC105 + capecitabine TRC105: IV (7.5 or 10 mg/kg weekly) Capecitabine: oral (1,000 mg/m2 BID)
    Period Title: 7.5 mg/kg TRC105, 1000 mg/m2 Cape
    STARTED 4
    COMPLETED 3
    NOT COMPLETED 1
    Period Title: 7.5 mg/kg TRC105, 1000 mg/m2 Cape
    STARTED 15
    COMPLETED 15
    NOT COMPLETED 0

    Baseline Characteristics

    Arm/Group Title Single
    Arm/Group Description All patients received TRC105 + capecitabine TRC105: IV (7.5 or 10 mg/kg weekly) Capecitabine: oral (1,000 mg/m2 BID)
    Overall Participants 19
    Age (Count of Participants)
    <=18 years
    0
    0%
    Between 18 and 65 years
    15
    78.9%
    >=65 years
    4
    21.1%
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    53
    Sex: Female, Male (Count of Participants)
    Female
    15
    78.9%
    Male
    4
    21.1%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    Asian
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    Black or African American
    4
    21.1%
    White
    15
    78.9%
    More than one race
    0
    0%
    Unknown or Not Reported
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    19
    100%

    Outcome Measures

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

    Outcome Measure Data

    Analysis Population Description
    All patients who received at least a portion of a dose of TRC105 enrolled in the dose escalation portion of the study
    Arm/Group Title Carotuximab (TRC105) Plus Capecitabine
    Arm/Group Description All patients received TRC105 + capecitabine TRC105: IV (7.5 or 10 mg/kg weekly) Capecitabine: oral (1,000 mg/m2 BID)
    Measure Participants 6
    Patients with DLT at 7.5 mg/kg
    0
    0%
    Patients without DLT at 7.5 mg/kg
    3
    15.8%
    Patients with DLT at 10 mg/kg
    0
    0%
    Patients without DLT at 10 mg/kg
    3
    15.8%
    2. Secondary Outcome
    Title TRC105 Steady State Pharmacokinetic Trough Concentration at the RP2D
    Description Mean trough concentration for patients dosed at 10 mg/kg at cycle 2 day 1
    Time Frame Cycle 2 day 1 (3 weeks)

    Outcome Measure Data

    Analysis Population Description
    All patients who received full TRC105 doses of 10 mg/kg in cycle 1.
    Arm/Group Title Single
    Arm/Group Description All patients dosed at 10 mg/kg TRC105 who received TRC105 + capecitabine TRC105: IV (10 mg/kg weekly) Capecitabine: oral (1,000 mg/m2 BID)
    Measure Participants 15
    Mean (Full Range) [ng/mL]
    66668.75
    3. Secondary Outcome
    Title Number of Patients With Positive Immune Response to TRC105
    Description 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.
    Time Frame 1.5 years

    Outcome Measure Data

    Analysis Population Description
    All patients who received at least a portion of a dose of TRC105
    Arm/Group Title Single
    Arm/Group Description All patients received TRC105 + capecitabine TRC105: IV Capecitabine: oral
    Measure Participants 19
    Post-Dose Positive Anti-Drug Antibody
    3
    15.8%
    Post-Dose Negative Anti-Drug Antibody
    16
    84.2%
    4. Secondary Outcome
    Title Number of Patients With Objective Response According to RECIST 1.1
    Description 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
    Time Frame 1.5 years

    Outcome Measure Data

    Analysis Population Description
    Patients who had measurable disease at baseline and received at least one follow up scan were evaluable for the primary efficacy outcome of ORR by RECIST 1.1
    Arm/Group Title Single
    Arm/Group Description All patients received TRC105 + capecitabine TRC105: IV Capecitabine: oral
    Measure Participants 16
    Partial Response
    1
    5.3%
    Stable Disease
    3
    15.8%
    Progressive Disease
    12
    63.2%

    Adverse Events

    Time Frame Adverse events are collected for each patient from the time of informed consent through 28 days following the last dose of study drug. Patients were eligible for participation in the trial until they progressed. The longest duration of AE collection for a given patient was 1 year.
    Adverse Event Reporting Description
    Arm/Group Title Single
    Arm/Group Description All patients received TRC105 + capecitabine TRC105: IV Capecitabine: oral
    All Cause Mortality
    Single
    Affected / at Risk (%) # Events
    Total 0/19 (0%)
    Serious Adverse Events
    Single
    Affected / at Risk (%) # Events
    Total 6/19 (31.6%)
    Blood and lymphatic system disorders
    Febrile neutropenia 1/19 (5.3%) 1
    General disorders
    Fatigue 1/19 (5.3%) 1
    Pyrexia 1/19 (5.3%) 1
    Injury, poisoning and procedural complications
    Fracture 1/19 (5.3%) 1
    Hip Fracture 1/19 (5.3%) 1
    Nervous system disorders
    Headache 1/19 (5.3%) 1
    Other (Not Including Serious) Adverse Events
    Single
    Affected / at Risk (%) # Events
    Total 19/19 (100%)
    Gastrointestinal disorders
    Gingival bleeding 7/19 (36.8%) 7
    Vomiting 5/19 (26.3%) 5
    Nausea 5/19 (26.3%) 5
    General disorders
    Fatigue 7/19 (36.8%) 7
    Injury, poisoning and procedural complications
    Infusion-related reactions 4/19 (21.1%) 4
    Nervous system disorders
    Headache 7/19 (36.8%) 7
    Respiratory, thoracic and mediastinal disorders
    Epistaxis 6/19 (31.6%) 6
    Skin and subcutaneous tissue disorders
    Rash 3/19 (15.8%) 3
    Vascular disorders
    Flushing 3/19 (15.8%) 3

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Charles Theuer, Medical Monitor
    Organization TRACON Pharmaceuticals Inc
    Phone 8585500780
    Email ctheuer@traconpharma.com
    Responsible Party:
    Tracon Pharmaceuticals Inc.
    ClinicalTrials.gov Identifier:
    NCT01326481
    Other Study ID Numbers:
    • 105BC102
    First Posted:
    Mar 31, 2011
    Last Update Posted:
    Mar 18, 2019
    Last Verified:
    Feb 1, 2019