A Study to Compare Tivozanib (AV-951) to Sorafenib in Subjects With Advanced Renal Cell Carcinoma

NCT01030783 | Completed Phase 3 Results DMC

• 1 other identifier: AV-951-09-301
• Study Type: interventional
• Target: 517
• Locations: 16 countries
• Sites: 86

Brief Summary

This is an open-label, randomized, controlled, multi-national, multi-center, parallel-arm trial comparing tivozanib to sorafenib in subjects with advanced RCC. The study is designed to compare the PFS, OS, ORR, DR, safety and tolerability, and kidney specific symptoms/health outcome measurements of tivozanib and sorafenib.

Conditions

Advanced Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS) of Subjects With Advanced Renal Cell Cancer (RCC) Randomized to Treatment With Tivozanib or Sorafenib

  Progression-Free Survival (PFS) is defined as the time from randomization to first documentation of objective tumor progression (progressive disease) or death due to any reasons whichever comes first. Disease progression per RECIST 1.0 criteria is defined 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.

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first. Disease progression was assessed every 8 weeks.

Secondary Outcomes (6)

• Overall Survival (OS) of Subjects Randomized to Treatment With Tivozanib or Sorafenib

  Date of randomization to date of death

• Objective Response Rate (ORR) of Subjects Randomized to Treatment With Tivozanib or Sorafenib

  Every 8 weeks from date of randomization until disease progression

• Duration of Response (DR) of Subjects Randomized to Treatment With Tivozanib or Sorafenib

  Assessed every 8 weeks from date of randomization until date of progression

• Safety and Tolerability of Tivozanib and Sorafenib

  From start of treatment therapy to completion of treatment therapy, an average of 11 months

• To Compare Kidney-specific Symptoms and Health Outcome Measurements in Subjects Randomized to Treatment With Tivozanib or Sorafenib

  At Day 1 of each 28 day cycle throughout the course of the study, for an average of 11 months per subject

Study Arms (2)

tivozanib (AV-951)

EXPERIMENTAL

Drug: tivozanib (AV-951)

sorafenib

ACTIVE COMPARATOR

Drug: Sorafenib

Interventions

tivozanib (AV-951) DRUG

Tivozanib: 1.5 mg orally once daily. Subjects will receive 1.5 mg tivozanib once daily beginning on Day 1 for 3 weeks followed by 1 week off treatment. One cycle will be defined as 4 weeks of treatment. Cycles will be repeated every 4 weeks.

tivozanib (AV-951)

Sorafenib DRUG

Sorafenib: 400 mg orally twice daily. Subjects will receive 400 mg (2 x 200 mg tablets) sorafenib twice daily continuously, beginning on Day 1. One cycle will be defined as 4 weeks of treatment. Cycles will be repeated every 4 weeks.

sorafenib

Eligibility Criteria

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

You may qualify if:

• ≥ 18-years of age.
• Subjects with recurrent or metastatic RCC.
• Subjects must have undergone prior nephrectomy (complete or partial) for excision of the primary tumor.
• Histologically or cytologically confirmed RCC with a clear cell component (subjects with pure papillary cell tumor or other non-clear cell histologies, including collecting duct, medullary, chromophobe, mixed tumor containing predominantly sarcomatoid cells, and unclassified RCC are excluded).
• Measurable disease per the RECIST criteria Version 1.0.
• Treatment naïve subjects or subjects who have received no more than one prior systemic treatment (immunotherapy, including interferon-alfa or interleukin-2 based therapy, chemotherapy, hormonal therapy or an investigational agent) for metastatic RCC. Postoperative or adjuvant systemic therapy will not be counted as a prior therapy unless recurrence is detected within 6 months of completion of treatment, in which case it will be counted as a prior therapy for metastatic disease.
• ECOG performance status of 0 or 1, and life expectancy ≥ 3 months.
• If female and of childbearing potential, documentation of negative pregnancy test prior to enrollment.
• Ability to give written informed consent and comply with protocol requirements.

You may not qualify if:

• Any prior VEGF-directed therapy including VEGF antibody (eg, bevacizumab), VEGF receptor tyrosine kinase inhibitor (eg, sunitinib, sorafenib, axitinib, pazopanib, etc.), VEGF trap (eg, aflibercept), or any other agent or investigational agent targeting the VEGF pathway.
• Any prior therapy with an agent targeting the mTOR pathway (eg, temsirolimus, everolimus, etc)
• Primary CNS malignancies or CNS metastases; subjects with previously treated brain metastasis will be allowed if the brain metastasis have been stable without steroid treatment for at least 3 months following prior treatment (radiotherapy or surgery).
• Any hematologic abnormalities (as noted in the protocol).
• Any serum chemistry abnormalities (as noted in the protocol).
• Significant cardiovascular disease.
• Non-healing wound, bone fracture, or skin ulcer.
• Active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis, or other gastrointestinal condition with increased risk of perforation; history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 4 weeks prior to administration of first dose of study drug.
• Serious/active infection or infection requiring parenteral antibiotics.
• Inadequate recovery from any prior surgical procedure or major surgical procedure within 4 weeks prior to administration of first dose of study drug.
• Significant thromboembolic or vascular disorders within 6 months prior to administration of first dose of study drug.
• Significant bleeding disorders within 6 months prior to administration of first dose of study drug.
• Currently active second primary malignancy, including hematologic malignancies (leukemia, lymphoma, multiple myeloma, etc.), other than non-melanoma skin cancers, non-metastatic prostate cancer, in situ cervical cancer and ductal or lobular carcinoma in situ of the breast. Subjects are not considered to have a currently active malignancy if they have completed anti-cancer therapy and have been disease free for \>2 years.
• Pregnant or lactating females.
• History of genetic or acquired immune suppression disease such as HIV; subjects on immune suppressive therapy for organ transplant.

Sponsors & Collaborators

• AVEO Pharmaceuticals, Inc.: lead

Study Sites (86)

Site 185

Los Angeles, California, 90095, United States

Location

Site 180

Gainesville, Florida, 32625, United States

Location

Site 184

Orlando, Florida, 32806, United States

Location

Site 182

Minneapolis, Minnesota, 55455, United States

Location

Site 186

New York, New York, 10065, United States

Location

Site 187

Dallas, Texas, 75246, United States

Location

Site 102

Sante Fe, 3077, Argentina

Location

Site 403

Plovdiv, 4004, Bulgaria

Location

Site 404

Sofia, 1431, Bulgaria

Location

Site 400

Sofia, 1756, Bulgaria

Location

Site 401

Varna, 9002, Bulgaria

Location

Site 402

Veliko Tarnovo, 5000, Bulgaria

Location

Site 110

Montreal, Quebec, H2X 1N8, Canada

Location

Site 121

La Reina, Santiago de Chile, 7510009, Chile

Location

Site 122

Santiago, 8320000, Chile

Location

Site 123

Temuco, 4810469, Chile

Location

Site 411

Prague, 180 81, Czechia

Location

Site 130

Marseille, 13009, France

Location

Site 133

Saint-Herblain, 44805, France

Location

Site 423

Budapest, H-1108, Hungary

Location

Site 421

Kaposvár, H-7400, Hungary

Location

Site 422

Pécs, H-7624, Hungary

Location

Site 424

Szombathely, H-9700, Hungary

Location

Site 157

Hyderabad, Andhra Pradesh, 500004, India

Location

Site 190

Patna, Bihar, 801505, India

Location

Site 156

Ahmedabad, Gujarat, 380015, India

Location

Site 151

Nashik, Maharashtra, 422005, India

Location

Site 153

Pune, Maharashtra, 411004, India

Location

Site 159

Pune, Maharashtra, 411005, India

Location

Site 191

Jaipur, Rajasthan, 302004, India

Location

Site 155

Jaipur, Rajasthan, 302013, India

Location

Site 152

Vellore, Tamil Nadu, 632004, India

Location

Site 158

Lucknow, Uttar Pradesh, 226003, India

Location

Site 150

Kolkata, West Bengal, 700054, India

Location

Site 154

Delhi, 110085, India

Location

Site 160

Arezzo, 52100, Italy

Location

Site 161

Pavia, 27100, Italy

Location

Site 162

Roma, 00152, Italy

Location

Site 432

Bialystok, 15-027, Poland

Location

Site 434

Bydgoszcz, 85-168, Poland

Location

Site 431

Gdansk, 80-952, Poland

Location

Site 435

Olsztyn, 10-228, Poland

Location

Site 433

Poznan, 61-878, Poland

Location

Site 430

Warsaw, 02-781, Poland

Location

Site 436

Warsaw, 04-141, Poland

Location

Site 444

Brasov, 500085, Romania

Location

Site 441

Bucharest, 022328, Romania

Location

Site 440

Bucharest, 041345, Romania

Location

Site 443

Bucharest, 050659, Romania

Location

Site 442

Timișoara, 300239, Romania

Location

Site 459

Ufa, Bashkortostan Republic, 450054, Russia

Location

Site 451

Chelyabinsk, 454087, Russia

Location

Site 452

Kazan', 420029, Russia

Location

Site 454

Moscow, 105077, Russia

Location

Site 453

Moscow, 115478, Russia

Location

Site 458

Moscow, 115478, Russia

Location

Site 460

Moscow, 115478, Russia

Location

Site 461

Moscow, 115478, Russia

Location

Site 462

Moscow, 125284, Russia

Location

Site 450

Nizhny Novgorod, 603109, Russia

Location

Site 456

Obninsk, 249036, Russia

Location

Site 467

Omsk, 644013, Russia

Location

Site 463

Pyatigorsk, 357500, Russia

Location

Site 457

Rostov-on-Don, 344022, Russia

Location

Site 466

Saint Petersburg, 193312, Russia

Location

Site 465

Saint Petersburg, 198255, Russia

Location

Site 464

Yaroslavi, 150054, Russia

Location

Site 455

Yekaterinburg, 620102, Russia

Location

Site 468

Yoshkar-Ola, 424037, Russia

Location

Site 480

Belgrade, 11000, Serbia

Location

Site 481

Belgrade, 11000, Serbia

Location

Site 482

Belgrade, 11000, Serbia

Location

Site 484

Kamenitz, 21204, Serbia

Location

Site 483

Niš, 18000, Serbia

Location

Site 491

Chernihiv, 14029, Ukraine

Location

Site 492

Dniproperovsk, 49102, Ukraine

Location

Site 498

Dnipropetrovsk, 49005, Ukraine

Location

Site 493

Donetsk, 83092, Ukraine

Location

Site 496

Donetsk, 83092, Ukraine

Location

Site 490

Ivano-Frankivsk, 76000, Ukraine

Location

Site 494

Kharkiv, 61037, Ukraine

Location

Site 497

Uzhhorod, 88014, Ukraine

Location

Site 495

Zaporizhia, 69600, Ukraine

Location

Site 170

Cambridge, CB2 0QQ, United Kingdom

Location

Site 173

Ipswich, IP4 5WW, United Kingdom

Location

Site 172

Leicester, LE1 5WW, United Kingdom

Location

Related Publications (1)

• Aldin A, Besiroglu B, Adams A, Monsef I, Piechotta V, Tomlinson E, Hornbach C, Dressen N, Goldkuhle M, Maisch P, Dahm P, Heidenreich A, Skoetz N. First-line therapy for adults with advanced renal cell carcinoma: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2023 May 4;5(5):CD013798. doi: 10.1002/14651858.CD013798.pub2.

  PMID: 37146227 DERIVED

Related Links

• Related Info

MeSH Terms

Interventions

tivozanib; Sorafenib

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Chief Medical Officer
• Organization: AVEO Pharmaceuticals, Inc.

Clinical@aveooncology.com

617-588-1960

Study Officials

• Robert J. Motzer, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2009
• First Posted: December 11, 2009
• Study Start: December 1, 2009
• Primary Completion: July 1, 2012
• Study Completion: June 1, 2013
• Last Updated: October 28, 2019
• Results First Posted: October 28, 2019

Record last verified: 2019-10

Locations

RO (5); UA (9); FR (2); CA (1); PL (7); BU (5); IT (3); CL (3); CZ (1); US (6); IN (12); GB (3); SE (5); HU (4); AR (1); RU (19)