Know Cancer

or
forgot password

A PHASE 1B DOSE-ESCALTION STUDY OF TRC105 IN COMBINATION WITH AXITINIB IN PATIENTS WITH ADVANCED RENAL CELL CARCINOMA


Phase 1
18 Years
N/A
Not Enrolling
Both
Renal Cell Carcinoma

Thank you

Trial Information

A PHASE 1B DOSE-ESCALTION STUDY OF TRC105 IN COMBINATION WITH AXITINIB IN PATIENTS WITH ADVANCED RENAL CELL CARCINOMA


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.


Inclusion Criteria:



1. Histologically confirmed advanced renal cell carcinoma that has progressed following
treatment with at least one multi-targeted tyrosine kinase inhibitor that targets the
VEGF receptor (e.g., sunitinib, pazopanib, sorafenib, tivozanib). Prior
immunotherapy, bevacizumab or mTOR inhibitor treatment is allowed. Prior axitinib is
allowed if the drug was not discontinued for toxicity.

2. No history of other carcinoma within the last five years, and/or where the risk of
recurrence is known to be under 5%

3. Measurable disease by RECIST 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. Willingness and ability to consent for self to participate in study

Exclusion Criteria:

1. Prior treatment with TRC105

2. Current treatment on another therapeutic clinical trial

3. Receipt of a small molecule anticancer agent, including an investigational anticancer
small molecule, within 14 days of starting study treatment

4. Receipt of a large molecule anticancer agent (e.g., antibody), including an
investigational anticancer antibody, within 28 days of starting study treatment

5. Prior surgery (including open biopsy) within 28 days of starting the study treatment
or the anticipated need for a major surgical procedure within the next six months

6. Prior radiation therapy within 28 days of starting the study treatment, except
radiation therapy for bone metastases is permitted up to 14 days of starting
treatment

7. Minor surgical procedures such as fine needle aspiration, Mediport placement or core
biopsy within 7 days of study treatment

8. 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
< 140/90 mm Hg)

9. Symptomatic ascites or pericardial or pleural effusion

10. 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 30 days.

11. Angina, MI, symptomatic congestive heart failure, cerebrovascular accident, transient
ischemic attack, arterial embolism, pulmonary embolism, Venous thrombosis, including
pulmonary embolism and deep venous thrombosis (unless adequately anticoagulated
without warfarin for more than two weeks), PTCA or CABG within the past 6 months

12. Active bleeding or pathologic condition that carries a high risk of bleeding (e.g.
hereditary hemorrhagic telangiectasia). Patients who have been uneventfully
anti-coagulated with low molecular weight heparin are eligible.

13. Thrombolytic use (except to maintain i.v. catheters) within 10 days prior to first
day of study therapy

14. Cardiac dysrhythmias of NCI CTCAE grade ≥ 2 within the last 28 days

15. Known active viral or nonviral hepatitis or cirrhosis

16. History of hemorrhage or hemoptysis (> ½ teaspoon bright red blood) within 6 months
of starting study treatment

17. 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.

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Determine Maximum Tolerated Dose of TRC105 in Combination with Axitinib

Outcome Description:

Safety and dose limiting toxicity will be assessed by dose cohort.

Outcome Time Frame:

1 Year

Safety Issue:

Yes

Authority:

United States: Food and Drug Administration

Study ID:

105RC101

NCT ID:

NCT01806064

Start Date:

March 2013

Completion Date:

May 2014

Related Keywords:

  • Renal Cell Carcinoma
  • TRC105
  • CD105
  • RCC
  • Renal Cell Carcinoma
  • Axitinib
  • INLYTA
  • Advanced Renal Cell Carcinoma
  • Carcinoma
  • Carcinoma, Renal Cell

Name

Location

Massachusetts General HospitalBoston, Massachusetts  02114-2617
University of Alabama at BirminghamBirmingham, Alabama  35294-3300
Dana Farber Cancer InstituteBoston, Massachusetts  02115