An Extension Treatment Protocol for Subjects Who Have Participated in a Study of Tivozanib Versus Sorafenib in Kidney Carcinoma (Protocol AV-951-09-301).

NCT01076010 | Completed Phase 3 Results

• 2 other identifiers: AV-951-09-9022009-015987-32
• Study Type: interventional
• Target: 277
• Locations: 15 countries
• Sites: 75

Brief Summary

Open-label, multi-center extension treatment protocol to allow access to tivozanib and sorafenib for subjects who have participated on the AV-951-09-301 protocol. Eligible subjects who were randomized to receive sorafenib on AV-951-09-301 and had documented progression of disease will receive a tivozanib dose of 1.5 mg/day. Eligible subjects who were randomized to tivozanib or sorafenib in AV-951-09-301, and displayed clinical benefit and acceptable tolerability to treatment, will continue to receive tivozanib or sorafenib at the same dose and schedule as in AV-951-09-301.

Conditions

Advanced Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (6)

• Number of Days Subjects Received Treatment in Each Treatment Arm

  Number of days subjects received treatment who were from Protocol AV-951-09-301 who either continued on tivozanib in this trial (subjects with first-line experience on tivozanib treatment), who crossed over from sorafenib to tivozanib in this trial (crossover subjects) participated in, and who continued on sorafenib in this trial (subjects with first-line experience on sorafenib treatment). Subjects could be discontinued due to unacceptable toxicities or clinical or documented PD

  From enrollment to until all subjects discontinue (due to documented progressive disease [PD] or unacceptable toxicities) or until 3 years after the first subject was enrolled in Protocol AV-951-09-902

• Number of Cycles Subjects Received Treatment in Each Treatment Arm

  Number of cycles subjects received who were from Protocol AV-951-09-301 who either continued on tivozanib in this trial (subjects with first-line experience on tivozanib treatment), who crossed over from sorafenib to tivozanib in this trial (crossover subjects) participated in, and who continued on sorafenib in this trial (subjects with first-line experience on sorafenib treatment). Subjects could be discontinued due to unacceptable toxicities or clinical or documented PD

  From enrollment to until all subjects discontinue (due to documented PD or unacceptable toxicities) or until 3 years after the first subject was enrolled in Protocol AV-951-09-902

• Total Dose Administered to Subjects in Each Treatment Arm (mg)

  The total dose administered to subjects who were from Protocol AV-951-09-301 who either continued on tivozanib in this trial (subjects with first-line experience on tivozanib treatment), who crossed over from sorafenib to tivozanib in this trial (crossover subjects) participated in, and who continued on sorafenib in this trial (subjects with first-line experience on sorafenib treatment). Subjects could be discontinued due to unacceptable toxicities or clinical or documented PD

  From enrollment to until all subjects discontinue (due to documented PD or unacceptable toxicities) or until 3 years after the first subject was enrolled in Protocol AV-951-09-902

• Average Daily Dose Administered to Subjects in Each Treatment Arm

  The average daily dose administered to subjects who were from Protocol AV-951-09-301 who either continued on tivozanib in this trial (subjects with first-line experience on tivozanib treatment), who crossed over from sorafenib to tivozanib in this trial (crossover subjects) participated in, and who continued on sorafenib in this trial (subjects with first-line experience on sorafenib treatment). Subjects could be discontinued due to unacceptable toxicities or clinical or documented PD

  From enrollment to until all subjects discontinue (due to documented PD or unacceptable toxicities) or until 3 years after the first subject was enrolled in Protocol AV-951-09-902

• Relative Dose Intensity (RDI) of Treatment Administered to Subjects in Each Treatment Arm

  RDI is defined as 100% times the actual dose intensity divided by the intended dose intensity. The RDI of subjects who were from Protocol AV-951-09-301 who either continued on tivozanib in this trial (subjects with first-line experience on tivozanib treatment), who crossed over from sorafenib to tivozanib in this trial (crossover subjects) participated in, and who continued on sorafenib in this trial (subjects with first-line experience on sorafenib treatment). Subjects could be discontinued due to unacceptable toxicities or clinical or documented PD

  From enrollment to until all subjects discontinue (due to documented PD or unacceptable toxicities) or until 3 years after the first subject was enrolled in Protocol AV-951-09-902

• Number of Subjects With Adverse Events

  Number of subjects with Treatment-Related Adverse Events (AEs) as assessed by Common Terminology Criteria for Adverse Events v3.0

  From enrollment assessed up to 3 years of treatment or until follow-up (up to 30 days end-of-trial visit after treatment discontinuation), whichever occurs earlier

Secondary Outcomes (4)

• Number of Subjects With Objective Response Rate (ORR) Who Continued Treatment With Tivozanib or Sorafenib and Who Received Tivozanib After Failure of Sorafenib

  From Day 1 to the end of treatment (EOT) Visit, approximately every 8 weeks

• Duration of Response (DR)

  From the first documentation of objective tumor response to the first documentation of objective tumor progression, assessed up to treatment discontinuation or to death due to any reason or maximum up to 3 years, whichever occurs earlier

• Progression-free Survival (PFS)

  From the date of first dose of study drug (tivozanib or sorafenib) in the AV-951-09-902 study to the first documentation of objective tumor progression or death due to any reason or maximum up to 3 years, whichever occurred first

• Overall Survival (OS)

  From the date of first dose of study drug (tivozanib or sorafenib) in the AV-951-09-902 study to death due to any reason or maximum up to 3 years, whichever occurred first

Study Arms (3)

Sorafenib crossover to tivozanib.

EXPERIMENTAL

The subjects who failed sorafenib (had Response Evaluation Criteria in Solid Tumors \[RECIST\] - defined progressive disease) on the parent protocol AV-951-09-301 will be offered tivozanib hydrochloride on Protocol AV- 951-09-902.

Drug: Tivozanib; Drug: Sorafenib

First line tivozanib.

EXPERIMENTAL

The subjects who were randomized to tivozanib (continued from the parent Protocol AV-951-09-301) and demonstrated clinical benefit and acceptable tolerability in Protocol AV-951-09-301.

Drug: Tivozanib

First line sorafenib.

ACTIVE COMPARATOR

The subjects who were randomized to sorafenib (continued from the parent Protocol AV-951-09-301) and demonstrated clinical benefit and acceptable tolerability were to be offered long-term access to sorafenib.

Drug: Sorafenib

Interventions

Tivozanib DRUG

Tivozanib capsules, administered orally, on a dosing schedule of 3 weeks of treatment (beginning on Day 1) followed by 1 week off treatment. One cycle was defined as 4 weeks of treatment.

First line tivozanib.; Sorafenib crossover to tivozanib.

Sorafenib DRUG

Sorafenib tablets, 400 mg twice daily, administered orally for 4 weeks (1 cycle = 4 weeks). One cycle was defined as 4 weeks of treatment. Cycles were repeated every 4 weeks.

First line sorafenib.; Sorafenib crossover to tivozanib.

Eligibility Criteria

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

You may qualify if:

• The subject must have participated on Protocol AV-951-09-301, and must meet either of the following bulleted criteria:
• Demonstrated disease progression per RECIST during treatment with sorafenib, OR
• Demonstrated clinical benefit \[complete response (CR), partial response (PR), or stable disease (SD) per RECIST\] and acceptable tolerability after treatment with tivozanib or sorafenib on protocol AV-951-09-301.
• Eastern Cooperative Oncology Group performance status ≤ 2 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

You may not qualify if:

• Newly identified central nervous system (CNS) malignancies or documented progression of CNS metastases; subjects will be allowed only if the CNS metastases have been adequately treated with radiotherapy or surgery. For subjects receiving steroid therapy for allowed steroid maintenance therapy.
• Duration since last dose on Protocol AV-951-09-301:
• For subjects continuing tivozanib or sorafenib (subjects who demonstrated clinical benefit and acceptable tolerability during treatment with tivozanib or sorafenib on protocol AV-951-09-301): more than 2 weeks since last dose of tivozanib or sorafenib.
• For subjects initiating tivozanib (ie demonstrated disease progression during treatment with sorafenib): more than 4 weeks since last dose of sorafenib. Subjects demonstrating disease progression due to CNS metastasis will be allowed up to 8 weeks since last dose of sorafenib in order to complete treatment for CNS metastasis.
• Inadequate recovery from any prior surgical procedure or major surgical procedure within 4 weeks prior to administration of first dose of study drug.
• Any of the following hematologic abnormalities:
• Hemoglobin \< 9.0 g/dL
• Absolute neutrophil count \< 1500 per mm3
• Platelet count \< 75,000 per mm3
• Prothrombin time or Partial thromboplastin time \>1.5 × upper limit of normal (ULN)
• Any of the following serum chemistry abnormalities:
• Total bilirubin \> 1.5 × ULN (or \> 2.5 × ULN for subjects with Gilbert's syndrome)
• Aspartate aminotransferase or alanine aminotransferase \> 2.5 × ULN (or \> 5 × ULN for subjects with liver metastasis)
• Alkaline phosphatase \> 2.5 × ULN (or \> 5 × ULN for subjects with liver or bone metastasis)
• Creatinine \> 2.0 × ULN

Sponsors & Collaborators

• AVEO Pharmaceuticals, Inc.: lead

Study Sites (75)

Site 185

Los Angeles, California, 90095, 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, 10065-6007, United States

Location

Site 187

Dallas, Texas, 75246, United States

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 122

Santiago, 8320000, Chile

Location

Site 123

Temuco, 4810469, Chile

Location

Site 411

Prague, 180 81, Czechia

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 156

Ahmedabad, Gujarat, 380015, India

Location

Site 151

Nashik, Maharashtra, 422005, India

Location

Site 153

Pune, Maharashtra, 411004, India

Location

Site 191

Jaipur, Rajasthan, 302004, 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

Yaroslavl, 150054, Russia

Location

Site 455

Yekaterinburg, 620102, 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 498

Dniproperovsk, 49005, Ukraine

Location

Site 492

Dniproperovsk, 49102, 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 172

Leicester, LE1 5WW, United Kingdom

Location

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: Cheif Medical officer
• Organization: AVEO Pharmaceuticals, Inc.

Clinical@aveooncology.com

857-400-0101

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: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 24, 2010
• First Posted: February 25, 2010
• Study Start: March 1, 2010
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: October 5, 2020
• Results First Posted: October 5, 2020

Record last verified: 2020-09

Locations

SE (5); PL (7); CZ (1); US (5); RU (18); IN (8); RO (5); FR (1); BU (5); UA (9); CA (1); GB (2); HU (3); IT (3); CL (2)