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

NCT ID: NCT01076010

Last Updated: 2020-10-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 277 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-03-31
• Study Completion Date: 2014-07-31

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.

Detailed Description

This is an extension treatment protocol to allow access to tivozanib or sorafenib for subjects enrolled on AV-951-09-301(parent protocol). Subjects who failed sorafenib on the parent protocol will be offered tivozanib. Subjects who were randomized to tivozanib, and demonstrated clinical benefit and acceptable tolerability will be offered long-term access to tivozanib. Subjects who were randomized to sorafenib, and demonstrated clinical benefit and acceptable tolerability will be offered long-term access to sorafenib. Subjects who continue receiving sorafenib on this protocol and progress will be allowed to cross-over to tivozanib.

Conditions

Advanced Renal Cell Carcinoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Sorafenib crossover to tivozanib.

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.

Group Type: EXPERIMENTAL

Tivozanib

Intervention Type: 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.

Sorafenib

Intervention Type: 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 tivozanib.

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.

Group Type: EXPERIMENTAL

Tivozanib

Intervention Type: 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 sorafenib.

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.

Group Type: ACTIVE_COMPARATOR

Sorafenib

Intervention Type: 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.

Interventions

Tivozanib

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.

Intervention Type: DRUG

Sorafenib

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. 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.

2. Eastern Cooperative Oncology Group performance status ≤ 2 and life expectancy ≥ 3 months.

3. If female and of childbearing potential, documentation of negative pregnancy test prior to enrollment.

4. Ability to give written informed consent

Exclusion Criteria

1. 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.

2. Duration since last dose on Protocol AV-951-09-301:

1. 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.

2. 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.

3. Inadequate recovery from any prior surgical procedure or major surgical procedure within 4 weeks prior to administration of first dose of study drug.

4. 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)

5. 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
• Proteinuria > 3+ by urinalysis or urine dipstick

6. If female, pregnant or lactating.

7. Sexually active pre-menopausal female subjects (and female partners of male subjects) must use adequate contraceptive measures, while on study and for at least 50 days after the last dose of study drug. Sexually active male subjects must use adequate contraceptive measures, while on study and for at least 90 days after the last dose of study drug. All fertile male and female subjects,and their partners,must agree to use a highly effective method of contraception. Effective birth control includes (a) Intrauterine device plus one barrier method; or (b) 2 barrier methods. Effective barrier methods are male or female condoms, diaphragms, and spermicides (creams or gels that contain a chemical to kill sperm). (Note: Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are not considered effective for this study).

8. Uncontrolled hypertension: systolic blood pressure > 150 mmHg or diastolic blood pressure >100 mmHg on 2 or more antihypertensive medications, documented on 2 consecutive measurements taken at least 24 hours apart.

9. Unhealed wounds (including active peptic ulcers).

10. Serious/active infection or infection requiring parenteral antibiotics.

11. Life-threatening illness or organ system dysfunction compromising safety evaluation.

12. Psychiatric disorder, altered mental status precluding informed consent or necessary testing.

13. Inability to comply with protocol requirements.

14. Treatment with another anti-cancer therapy or participation in another interventional protocol (excluding AV-951-09-301).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AVEO Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Robert J. Motzer, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

Site 185

Los Angeles, California, United States

Site 184

Orlando, Florida, United States

Site 182

Minneapolis, Minnesota, United States

Site 186

New York, New York, United States

Site 187

Dallas, Texas, United States

Site 403

Plovdiv, , Bulgaria

Site 404

Sofia, , Bulgaria

Site 400

Sofia, , Bulgaria

Site 401

Varna, , Bulgaria

Site 402

Veliko Tarnovo, , Bulgaria

Site 110

Montreal, Quebec, Canada

Site 122

Santiago, , Chile

Site 123

Temuco, , Chile

Site 411

Prague, , Czechia

Site 133

Saint-Herblain, , France

Site 423

Budapest, , Hungary

Site 421

Kaposvár, , Hungary

Site 422

Pécs, , Hungary

Site 156

Ahmedabad, Gujarat, India

Site 151

Nashik, Maharashtra, India

Site 153

Pune, Maharashtra, India

Site 191

Jaipur, Rajasthan, India

Site 152

Vellore, Tamil Nadu, India

Site 158

Lucknow, Uttar Pradesh, India

Site 150

Kolkata, West Bengal, India

Site 154

Delhi, , India

Site 160

Arezzo, , Italy

Site 161

Pavia, , Italy

Site 162

Roma, , Italy

Site 432

Bialystok, , Poland

Site 434

Bydgoszcz, , Poland

Site 431

Gdansk, , Poland

Site 435

Olsztyn, , Poland

Site 433

Poznan, , Poland

Site 430

Warsaw, , Poland

Site 436

Warsaw, , Poland

Site 444

Brasov, , Romania

Site 441

Bucharest, , Romania

Site 440

Bucharest, , Romania

Site 443

Bucharest, , Romania

Site 442

Timișoara, , Romania

Site 459

Ufa, Bashkortostan Republic, Russia

Site 451

Chelyabinsk, , Russia

Site 452

Kazan', , Russia

Site 454

Moscow, , Russia

Site 453

Moscow, , Russia

Site 458

Moscow, , Russia

Site 460

Moscow, , Russia

Site 461

Moscow, , Russia

Site 462

Moscow, , Russia

Site 450

Nizhny Novgorod, , Russia

Site 456

Obninsk, , Russia

Site 467

Omsk, , Russia

Site 463

Pyatigorsk, , Russia

Site 457

Rostov-on-Don, , Russia

Site 466

Saint Petersburg, , Russia

Site 465

Saint Petersburg, , Russia

Site 464

Yaroslavl, , Russia

Site 455

Yekaterinburg, , Russia

Site 480

Belgrade, , Serbia

Site 481

Belgrade, , Serbia

Site 482

Belgrade, , Serbia

Site 484

Kamenitz, , Serbia

Site 483

Niš, , Serbia

Site 491

Chernihiv, , Ukraine

Site 498

Dniproperovsk, , Ukraine

Site 492

Dniproperovsk, , Ukraine

Site 493

Donetsk, , Ukraine

Site 496

Donetsk, , Ukraine

Site 490

Ivano-Frankivsk, , Ukraine

Site 494

Kharkiv, , Ukraine

Site 497

Uzhhorod, , Ukraine

Site 495

Zaporizhia, , Ukraine

Site 170

Cambridge, , United Kingdom

Site 172

Leicester, , United Kingdom

Countries

United States; Bulgaria; Canada; Chile; Czechia; France; Hungary; India; Italy; Poland; Romania; Russia; Serbia; Ukraine; United Kingdom

Related Links

http://www.aveopharma.com

Related Info

Other Identifiers

2009-015987-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

AV-951-09-902

Identifier Type: -

Identifier Source: org_study_id