Open Label Dose-Finding Study of TRC105 Plus Capecitabine for Metastatic Breast Cancer
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
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Single All patients received TRC105 + capecitabine |
Drug: TRC105
IV
Other Names:
Drug: Capecitabine
oral
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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
- 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
- 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.
- 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
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.- 105BC102
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
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%
|
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
|
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%
|
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
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 |
ctheuer@traconpharma.com |
- 105BC102