Clinical Trials /

Randomized Phase 2 Trial of Axitinib and TRC105 Versus Axitinib Alone in Patients Renal Cell Carcinoma

NCT01806064

Description:

Phase 1b: To evaluate safety and tolerability and determine a recommended phase 2 dose for TRC105 when added to standard dose axitinib in patients with advanced renal cell carcinoma. Phase 2: To estimate the PFS of patients with advanced or metastatic RCC by RECIST 1.1 criteria in patients treated with axitinib and TRC105 compared to those treated with axitinib alone, following failure of one prior VEGF TKI

Related Conditions:
  • Clear Cell Renal Cell Carcinoma
Recruiting Status:

Terminated

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Randomized Phase 2 Trial of Axitinib and TRC105 Versus Axitinib Alone in Patients With Advanced or Metastatic Renal Cell Carcinoma
  • Official Title: A Randomized Phase 2 Trial of Axitinib and TRC105 Versus Axitinib Alone (Including a lead-in Phase 1B Dose Escalation Portion) in Patients With Advanced or Metastatic Renal Cell Carcinoma

Clinical Trial IDs

  • ORG STUDY ID: 105RC101
  • NCT ID: NCT01806064

Conditions

  • Renal Cell Carcinoma

Interventions

DrugSynonymsArms
TRC105 and AxitinibChimeric Antibody (TRC105) to CD105, InlytaTRC105 and Axitinib
AxitinibInlytaAxitinib

Purpose

Phase 1b: To evaluate safety and tolerability and determine a recommended phase 2 dose for TRC105 when added to standard dose axitinib in patients with advanced renal cell carcinoma. Phase 2: To estimate the PFS of patients with advanced or metastatic RCC by RECIST 1.1 criteria in patients treated with axitinib and TRC105 compared to those treated with axitinib alone, following failure of one prior VEGF TKI

Detailed Description

      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.
    

Trial Arms

NameTypeDescriptionInterventions
TRC105 and AxitinibExperimental
  • TRC105 and Axitinib
AxitinibActive Comparator
  • Axitinib

Eligibility Criteria

        Inclusion Criteria:

          1. Histologically confirmed advanced or metastatic renal cell carcinoma with a clear cell
             component that has progressed by investigator assessment following treatment with one
             and only one multi-targeted tyrosine kinase inhibitor (TKI) other than axitinib that
             targets the VEGF receptor (VEGFR) (e.g., sunitinib, pazopanib, sorafenib, tivozanib,
             cabozantinib). One prior immunotherapy (interleukin-2 or interferon-alpha or immune
             checkpoint inhibitor or tumor vaccine) and one prior mTOR inhibitor treatment are
             allowed.

          2. No other prior malignancy is allowed except for the following: adequately treated
             basal cell or squamous cell skin cancer, adequately treated Stage I or II cancer from
             which the patient is currently in complete remission per investigators' clinical
             judgment.

          3. Measurable disease by RECIST 1.1 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. Adequate organ function as defined by the following criteria:

          8. Willingness and ability to consent for self to participate in study

          9. Willingness and ability to comply with scheduled visits, treatment plan, laboratory
             tests, and other study procedures

        Exclusion Criteria:

          1. Prior treatment with TRC105 or axitinib or any agent targeting the endoglin pathway
             (including a fusion protein that binds bone morphogenic protein)

          2. Grade 3 or 4 toxicity related to prior VEGFR TKI that did not resolve to grade 1

          3. Current treatment on another therapeutic clinical trial

          4. Receipt of a small molecule anticancer agent, including an investigational anticancer
             small molecule, within 14 days of starting study treatment or receipt of a biologic
             anticancer agent (e.g., antibody) within 28 days of starting study treatment.

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

          6. No major surgical procedure or significant traumatic injury within 6 weeks prior to
             study registration, and must have fully recovered from any such procedure; date of
             surgery (if applicable). Note: the following are not considered to be major procedures
             and are permitted up to 7 days before therapy initiation: Thoracentesis, paracentesis,
             port placement, laparoscopy, thorascopy, tube thoracostomy, bronchoscopy, endoscopic
             ultrasonographic procedures, mediastinoscopy, skin biopsies, incisional biopsies,
             imaging-guided biopsy for diagnostic purposes, and routine dental procedures

          7. 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 <
             150/90 mm Hg)

          8. 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 28 days.

          9. Angina, MI, symptomatic congestive heart failure, cerebrovascular accident, transient
             ischemic attack, arterial embolism, pulmonary embolism, PTCA or CABG within the past 6
             months. Deep venous thrombosis within 6 months unless the patient is anticoagulated
             without the use of warfarin for at least 2 weeks. In this situation, low molecular
             weight heparin is preferred.

         10. Active bleeding or pathologic condition that carries a high risk of bleeding (e.g.
             hereditary hemorrhagic telangiectasia).

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

         12. Known active viral or nonviral hepatitis or cirrhosis

         13. History of hemorrhage or hemoptysis (> ½ teaspoon bright red blood) within 3 months of
             starting study treatment

         14. History of peptic ulcer disease within 3 months of treatment, unless treated for the
             condition and complete resolution has been documented by esophagogastroduodenoscopy
             (EGD) within 28 days of starting study treatment

         15. History of gastrointestinal perforation or fistula in the past 6 months, or while
             previously on antiangiogenic therapy, unless underlying risk has been resolved (e.g.,
             through surgical resection or repair)

         16. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)
             related illness

         17. Requirement for concomitant medications that strongly induce or inhibit CYP3A4/5

         18. 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. All female patients
             of reproductive potential must have a negative pregnancy test (serum or urine) within
             7 days prior to first dose. Male patients must be surgically sterile or must agree to
             use effective contraception during the study and for 3 months following last dose of
             TRC105. The definition of effective contraception will be based on the judgment of the
             Principal Investigator or a designated associate.

         19. Other severe acute or chronic medical or psychiatric condition or laboratory
             abnormality that may increase the risk associated with study participation or may
             interfere with the interpretation of study results and, in the judgment of the
             Investigator, would make the patient inappropriate for this study
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase 1b
Time Frame:1 Year
Safety Issue:
Description:To evaluate safety and tolerability and determine a recommended phase 2 dose for TRC105 when added to standard dose axitinib in patients with advanced renal cell carcinoma

Secondary Outcome Measures

Measure:Phase 1b:
Time Frame:1 Year
Safety Issue:
Description:To look for preliminary evidence of antitumor activity when TRC105 is added to axitinib, by assessing overall response rate and progression-free survival To characterize the pharmacokinetic profile of TRC105 when given with axitinib To evaluate TRC105 immunogenicity by measuring human antimurine antibody (HAMA) and human antichimeric antibody (HACA) formation To explore the pharmacodynamic changes in circulating angiogenic biomarkers following treatment with TRC105 and axitinib
Measure:Phase 2
Time Frame:15 Months
Safety Issue:
Description:To estimate overall response rate by RECIST 1.1 and Choi criteria, including duration of response by RECIST 1.1 To estimate the disease control rate (CR + PR + SD) at 12 weeks by RECIST 1.1 and Choi criteria, and to estimate the time to next metastasis To determine the frequency and severity of adverse events as assessed by NCI CTCAE (Version 4.0) To evaluate TRC105 immunogenicity as measured by human anti-murine antibody (HAMA) and human anti-chimeric antibody (HACA) concentrations To explore the effects of TRC105 on circulating angiogenic protein biomarkers

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Tracon Pharmaceuticals Inc.

Trial Keywords

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

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