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

NCT01806064 | Terminated Phase 1 Results DMC

• 1 other identifier: 105RC101
• Study Type: interventional
• Target: 173
• Locations: 4 countries
• Sites: 39

Brief Summary

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

Conditions

Renal Cell Carcinoma

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Phase 1b: Number of Patients With DLT

  Phase 1b: For dose limiting toxicity (DLT) evaluation, severity (grade) was classified according to common terminology criteria for adverse events version 4.0 (CTCAE v4.0).

  12 Months

• Phase 2: Progression Free Survival (PFS) of Patients With RCC

  Median progression free survival (PFS) of patients with advanced or metastatic RCC by RECIST 1.1. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

  15 Months

Secondary Outcomes (4)

• Phase 1b & 2: Response Rate of Patients With RCC

  15 Months

• Phase 2: Overall Response Rate of Patients With RCC by Choi

  15 Months

• Phase 1b & 2: Trough Concentrations of TRC105 by Dose Level in Phase 1b

  2.5 months (cycle 2 day 15)

• Phase 1b & 2: Number of Patients With Development of Immunogenicity Antibodies.

  12 months

Study Arms (2)

TRC105 and Axitinib

EXPERIMENTAL

Patients randomized to receive TRC105 at 3 mg/kg on day 1, 7 mg/kg on day 4, and 10 mg/kg on day 8 and weekly thereafter in combination with axitinib 5 mg twice daily

Drug: TRC105 and Axitinib

Axitinib

ACTIVE COMPARATOR

Patients randomized to receive axitinib 5 mg twice daily

Drug: Axitinib

Interventions

TRC105 and Axitinib DRUG

Also known as: Chimeric Antibody (TRC105) to CD105, Inlyta

TRC105 and Axitinib

Axitinib DRUG

Also known as: Inlyta

Axitinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• Measurable disease by RECIST 1.1 criteria
• Age of 18 years or older
• ECOG performance status ≤ 1
• Resolution of all acute adverse events resulting from prior cancer therapies to NCI CTCAE grade ≤ 1 or baseline (except alopecia)
• Adequate organ function as defined by the following criteria:
• Willingness and ability to consent for self to participate in study
• Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures

You may not qualify if:

• Prior treatment with TRC105 or axitinib or any agent targeting the endoglin pathway (including a fusion protein that binds bone morphogenic protein)
• Grade 3 or 4 toxicity related to prior VEGFR TKI that did not resolve to grade 1
• Current treatment on another therapeutic clinical trial
• 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.
• 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
• 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
• 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)
• 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.
• 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.
• Active bleeding or pathologic condition that carries a high risk of bleeding (e.g. hereditary hemorrhagic telangiectasia).
• Thrombolytic use (except to maintain i.v. catheters) within 10 days prior to first day of study therapy
• Known active viral or nonviral hepatitis or cirrhosis
• History of hemorrhage or hemoptysis (\> ½ teaspoon bright red blood) within 3 months of starting study treatment
• 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
• 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)

Sponsors & Collaborators

• Tracon Pharmaceuticals Inc.: lead

Study Sites (39)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Mayo Clinic Arizona

Scottsdale, Arizona, 85054, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

St. Joseph Heritage Healthcare

Fullerton, California, 92805, United States

Location

University of California, Irvine

Irvine, California, 92697, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

University of California, Davis

Sacramento, California, 95616, United States

Location

University of Florida

Gainesville, Florida, 32611, United States

Location

University of Miami

Miami, Florida, 33124, United States

Location

Moffitt Cancer Center

Tampa, Florida, 100271, United States

Location

Illinois CancerCare

Peoria, Illinois, 61615, United States

Location

Indiana Univeristy

Indianapolis, Indiana, 47405, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

University of Kentucky

Lexington, Kentucky, 40526, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 220071, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Washington University in St. Louis

St Louis, Missouri, 63110, United States

Location

Nebraska Cancer Specialists

Omaha, Nebraska, 68124, United States

Location

Atlantic Health System

Morristown, New Jersey, 07960, United States

Location

Gabrail Cancer Center Research

Canton, Ohio, 44718, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

Joe Arrington Cancer Research & Treatment Center

Lubbock, Texas, 79410, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Masaryk Institute

Brno, Czechia

Location

St. Anne's

Brno, Czechia

Location

University Hospital Brno

Brno, Czechia

Location

Na Bulovce Hospital

Prague, Czechia

Location

Thomayer Hospital

Prague, Czechia

Location

Integrated Szent Istvan and Szent Laszlo Hospital

Budapest, Hungary

Location

National Institute of Oncology

Budapest, Hungary

Location

University of Debrecen Medical Center Institute of Oncology

Debrecen, Hungary

Location

Kaposi Mor Teaching Hospital

Kaposvár, Hungary

Location

Medical Center of the University of Pecs

Pécs, Hungary

Location

Sussex Cancer Center, Royal Sussex County Hospital

Brighton, East Sussex, United Kingdom

Location

Related Publications (1)

• Choueiri TK, Michaelson MD, Posadas EM, Sonpavde GP, McDermott DF, Nixon AB, Liu Y, Yuan Z, Seon BK, Walsh M, Jivani MA, Adams BJ, Theuer CP. An Open Label Phase Ib Dose Escalation Study of TRC105 (Anti-Endoglin Antibody) with Axitinib in Patients with Metastatic Renal Cell Carcinoma. Oncologist. 2019 Feb;24(2):202-210. doi: 10.1634/theoncologist.2018-0299. Epub 2018 Sep 6.

  PMID: 30190302 DERIVED

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

carotuximab; Axitinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Indazoles; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

The study was terminated early due to lack of efficacy therefore protein biomarkers (P1b and P2), PK (P2), immunogenicity (P2) and disease control rate at 16 weeks by RECIST 1.1 and Choi criteria were not analyzed.

Results Point of Contact

• Title: Charles Theuer
• Organization: TRACON Pharmaceuticals Inc.

ctheuer@traconpharma.com

(858) 550-0780

Study Officials

• Charles Theuer, MD PhD

  ctheuer@traconpharma.com

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2013
• First Posted: March 7, 2013
• Study Start: March 8, 2013
• Primary Completion: December 21, 2018
• Study Completion: June 12, 2019
• Last Updated: October 19, 2020
• Results First Posted: October 19, 2020

Record last verified: 2020-10

Locations

HU (5); CZ (5); GB (1); US (28)