Trebananib With or Without Bevacizumab, Pazopanib Hydrochloride, Sorafenib Tosylate, or Sunitinib Malate in Treating Patients With Advanced Kidney Cancer

NCT01664182 | Completed Phase 2 Results

• 7 other identifiers: NCI-2012-01289PHII-122P9048_A12PAMDREVW01CDR00007387859048N01CM00038P30CA033572
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 12

Brief Summary

This randomized phase II trial studies how well trebananib with or without bevacizumab, pazopanib hydrochloride, sorafenib tosylate, or sunitinib malate works in treating patients with kidney cancer that has spread to other places in the body and usually cannot be cured or controlled with treatment (advanced). Trebananib may stop the growth of tumor cells by blocking blood flow to the tumor. Immunotherapy with monoclonal, such as bevacizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Pazopanib hydrochloride, sorafenib tosylate, and sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the tumor. It is not yet known whether giving trebananib with or without bevacizumab, pazopanib hydrochloride, sorafenib tosylate, or sunitinib malate is more effective in treating kidney cancer.

Conditions

Advanced Renal Cell Carcinoma; Advanced Sarcomatoid Renal Cell Carcinoma; Stage III Renal Cell Cancer AJCC v7; Stage IV Renal Cell Cancer AJCC v7

Outcome Measures

Primary Outcomes (2)

• Observed Response Rate

  Defined as the total number of efficacy-evaluable patients who achieve a complete or partial response by RECIST version 1.1 criteria, assessed by MRI: Complete Response (CR), Disappearance of all target lesions: any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm; Partial Response (PR), \>= 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Best response will be listed for each patient and summarized using standard descriptive methods-point estimate and associated confidence intervals.

  Up to 8 weeks

• Tumor Response

  Tumor Response Classification

  at 8 weeks

Secondary Outcomes (2)

• Progression Free Survival (PFS)

  From start of treatment to time of progression or death, whichever occurs first, assessed up to 8 weeks

• Number of Participants With Grade 3, 4, 5 Toxicities Related to the Treatment Drugs

  8 weeks for adverse events. Until removal from the study or to death for late adverse events, up to 12 weeks

Other Outcomes (1)

• Changes in Circulating Angiogenic Factors

  Baseline to up to 8 weeks

Study Arms (2)

Arm I (trebananib monotherapy)

EXPERIMENTAL

Patients receive trebananib IV over 30-60 minutes on days 1, 8, 15, 22, 29, and 36. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity.

Biological: Trebananib

Arm II (trebananib and anti-VEGF therapy)

EXPERIMENTAL

Patients receive trebananib as in Arm I and either bevacizumab IV over 30-90 minutes on days 1, 15, and 29, pazopanib hydrochloride PO QD on days 1-42, sorafenib tosylate PO BID on days 1-42, or sunitinib malate PO QD on days 1-28. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity.

Biological: Bevacizumab; Drug: Pazopanib Hydrochloride; Drug: Sorafenib Tosylate; Drug: Sunitinib Malate; Biological: Trebananib

Interventions

Bevacizumab BIOLOGICAL

Given IV

Also known as: Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF rhuMAb, Avastin, Bevacizumab awwb, Bevacizumab Biosimilar BEVZ92, Bevacizumab Biosimilar BI 695502, Bevacizumab Biosimilar CBT 124, Bevacizumab Biosimilar CT-P16, Bevacizumab Biosimilar FKB238, Bevacizumab Biosimilar GB-222, Bevacizumab Biosimilar HD204, Bevacizumab Biosimilar HLX04, Bevacizumab Biosimilar IBI305, Bevacizumab Biosimilar LY01008, Bevacizumab Biosimilar MIL60, Bevacizumab Biosimilar QL 1101, Bevacizumab Biosimilar RPH-001, Bevacizumab Biosimilar SCT501, BP102, BP102 Biosimilar, HD204, Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer, Recombinant Humanized Anti-VEGF Monoclonal Antibody, rhuMab-VEGF, SCT501

Arm II (trebananib and anti-VEGF therapy)

Pazopanib Hydrochloride DRUG

Given PO

Also known as: GW786034B, Votrient

Arm II (trebananib and anti-VEGF therapy)

Sorafenib Tosylate DRUG

Given PO

Also known as: BAY 43-9006 Tosylate, BAY 54-9085, Nexavar, sorafenib

Arm II (trebananib and anti-VEGF therapy)

Sunitinib Malate DRUG

Given PO

Also known as: SU011248, SU11248, sunitinib, Sutent

Arm II (trebananib and anti-VEGF therapy)

Trebananib BIOLOGICAL

Given IV

Also known as: AMG 386, AMG386, Angiopoietin 1/2-Neutralizing Peptibody AMG 386

Arm I (trebananib monotherapy); Arm II (trebananib and anti-VEGF therapy)

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically or cytologically confirmed renal cell carcinoma except medullary or collecting duct subtypes; sarcomatoid differentiation will be allowed
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>= 20 mm with conventional techniques or as \>= 10 mm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
• Patients must have documented radiologic or clinical progressive disease following at least one prior anti-VEGF regimen administered either as a single agent or in combination with other agents for at least 8 weeks; the prior anti-VEGF treatment regimen must have included bevacizumab, pazopanib, sorafenib or sunitinib administered not more than 12 weeks before study entry; Note: enrollment not more than 8 weeks after the last dose of anti-VEGF therapy is encouraged; nevertheless, intercurrent therapy with an mTOR inhibitor (everolimus or temsirolimus) will be allowed if progression on that treatment is observed within 12 weeks of the prior anti-VEGF therapy
• Any number of prior regimens is allowed; prior investigational therapy is allowed
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 70%)
• Life expectancy of greater than 3 months
• Leukocytes \>= 3,000/mcL
• Absolute neutrophil count \>= 1,500/mcL
• Platelets \>= 100,000/mcL
• Total bilirubin =\< institutional upper limits of normal
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional upper limit of normal
• Partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) =\< upper limit of normal (ULN) per institutional laboratory range
• International normalized ratio (INR) =\< 1.5
• Creatinine within normal institutional limits OR creatinine clearance \> 40 mL/min per 24 hour (h) urine collection or calculated according to the Cockcroft-Gault formula
• Urinary protein =\< 100 mg/dL in urinalysis or =\< 1+ on dipstick, unless quantitative protein is \< 1000 mg in a 24 h urine sample

You may not qualify if:

• Intolerance of prior treatment with bevacizumab, pazopanib, sorafenib, or sunitinib; Note: subjects who required a dose reduction of pazopanib, sorafenib, or sunitinib during prior therapy MAY be eligible if they tolerated the agent after dose level reduction (to a minimum of dose level -2 as defined in this protocol)
• Central nervous system metastases unless: (1) metastases have been treated and have remained controlled for at least two weeks following treatment, AND (2) patient has no residual neurological dysfunction off corticosteroids for at least one week; a CT or MRI to evaluate for central nervous system (CNS) disease is required for symptomatic patients only
• History of venous or arterial thromboembolism within 12 months prior to enrollment/randomization
• History of clinically significant bleeding within 6 months of enrollment/randomization
• Unresolved toxicities from prior systemic therapy that are Common Terminology Criteria in Adverse Events (CTCAE) version 3.0 or 4.0 \>= grade 2 in severity except alopecia
• Currently or previously treated with AMG 386, or other molecules that inhibit the angiopoietins or Tie2 receptor
• Clinically significant cardiovascular disease within 12 months prior to enrollment/randomization, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure, or arrhythmias not controlled by outpatient medication or placement of percutaneous transluminal coronary angioplasty/stent
• Major surgery within 28 days prior to enrollment or still recovering from prior surgery
• Minor surgical procedures except placement of tunneled central venous access device within 3 days prior to enrollment
• Non-healing wound, ulcer (including gastrointestinal), or fracture
• Subject not consenting to the use of highly effective contraceptive precautions (e.g., double barrier method \[i.e., condom plus diaphragm\]) during the course of the study and for 6 months after administration of the last study medication
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to AMG 386 or the anti-VEGF agent used in study
• History of allergic reactions to bacterially-produced proteins
• Patients who have had anti-VEGFR tyrosine kinase inhibitor within 1 week, mTOR inhibitor within 1 week or anti-VEGF antibody therapy within 3 weeks prior to entering the study; patients who have had other forms of chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
• Patients who have not yet completed at least 21 days (30 days for prior monoclonal antibody therapy) since ending other investigational device or drug trials, or who are currently receiving other investigational treatments

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (12)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

City of Hope South Pasadena

South Pasadena, California, 91030, United States

Location

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Metro Minnesota Community Oncology Research Consortium

Saint Louis Park, Minnesota, 55416, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, 17033-0850, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

VCU Massey Cancer Center at Hanover Medical Park

Mechanicsville, Virginia, 23116, United States

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Bevacizumab; Immunoglobulin G; Disulfides; pazopanib; Sorafenib; Sunitinib; trebananib

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)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immunoglobulin Isotypes; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals; Phenylurea Compounds; Urea; Amides; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Pyrroles; Azoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Thomas J Semrad, MD, MAS
• Organization: Gene Upshaw Memorial Tahoe Forest Cancer Center, Truckee, CA 96161

tsemrad@tfhd.com

+1 530 582 6450

Study Officials

• Thomas J Semrad

  City of Hope Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 10, 2012
• First Posted: August 14, 2012
• Study Start: August 1, 2012
• Primary Completion: December 7, 2020
• Study Completion: December 7, 2020
• Last Updated: June 7, 2022
• Results First Posted: June 7, 2022

Record last verified: 2022-05

Locations

US (12)