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

NCT ID: NCT01030783

Last Updated: 2019-10-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 517 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-12-31
• Study Completion Date: 2013-06-30

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.

Detailed Description

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.

Subjects will be randomized (1:1) to treatment with tivozanib or sorafenib and stratified by geographic region (North America/Western Europe, Central/Eastern Europe, or rest of the world); number of prior treatments (0 or 1); and number of metastatic sites/organs involved (1 or ≥ 2).

Conditions

Advanced Renal Cell Carcinoma

Study Design

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

Study Groups

tivozanib (AV-951)

Group Type: EXPERIMENTAL

tivozanib (AV-951)

Intervention Type: 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.

sorafenib

Group Type: ACTIVE_COMPARATOR

Sorafenib

Intervention Type: 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.

Interventions

tivozanib (AV-951)

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.

Intervention Type: DRUG

Sorafenib

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. ≥ 18-years of age.

2. Subjects with recurrent or metastatic RCC.

3. Subjects must have undergone prior nephrectomy (complete or partial) for excision of the primary tumor.

4. 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).

5. Measurable disease per the RECIST criteria Version 1.0.

6. 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.

7. ECOG performance status of 0 or 1, and life expectancy ≥ 3 months.

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

9. Ability to give written informed consent and comply with protocol requirements.

Exclusion Criteria

1. 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.

2. Any prior therapy with an agent targeting the mTOR pathway (eg, temsirolimus, everolimus, etc)

3. 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).

4. Any hematologic abnormalities (as noted in the protocol).

5. Any serum chemistry abnormalities (as noted in the protocol).

6. Significant cardiovascular disease.

7. Non-healing wound, bone fracture, or skin ulcer.

8. 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.

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

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

11. Significant thromboembolic or vascular disorders within 6 months prior to administration of first dose of study drug.

12. Significant bleeding disorders within 6 months prior to administration of first dose of study drug.

13. 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.

14. Pregnant or lactating females.

15. History of genetic or acquired immune suppression disease such as HIV; subjects on immune suppressive therapy for organ transplant.

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

17. Requirement for hemodialysis or peritoneal dialysis.

18. Inability to swallow pills, malabsorption syndrome or gastrointestinal disease that severely affects the absorption of tivozanib or sorafenib, major resection of the stomach or small bowel, or gastric bypass procedure.

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

20. Sexually active pre-menopausal female subjects (and female partners of male subjects) must use adequate contraceptive measures, while on study and for 50 days after the last dose of study drug. Sexually active male subjects must use adequate contraceptive measures, while on study for at least 90 days after the last dose of drug. All fertile male and female subjects and their partners must agree to use a highly effective method of contraception (including their partner). Effective birth control includes (a) IUD 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.)

• 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 180

Gainesville, Florida, 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 102

Sante Fe, , Argentina

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 121

La Reina, Santiago de Chile, Chile

Site 122

Santiago, , Chile

Site 123

Temuco, , Chile

Site 411

Prague, , Czechia

Site 130

Marseille, , France

Site 133

Saint-Herblain, , France

Site 423

Budapest, , Hungary

Site 421

Kaposvár, , Hungary

Site 422

Pécs, , Hungary

Site 424

Szombathely, , Hungary

Site 157

Hyderabad, Andhra Pradesh, India

Site 190

Patna, Bihar, India

Site 156

Ahmedabad, Gujarat, India

Site 151

Nashik, Maharashtra, India

Site 153

Pune, Maharashtra, India

Site 159

Pune, Maharashtra, India

Site 191

Jaipur, Rajasthan, India

Site 155

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

Yaroslavi, , Russia

Site 455

Yekaterinburg, , Russia

Site 468

Yoshkar-Ola, , 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 492

Dniproperovsk, , Ukraine

Site 498

Dnipropetrovsk, , 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 173

Ipswich, , United Kingdom

Site 172

Leicester, , United Kingdom

Countries

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

References

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.

Reference Type: DERIVED

PMID: 37146227 (View on PubMed)

Related Links

http://www.aveopharma.com

Related Info

Other Identifiers

AV-951-09-301

Identifier Type: -

Identifier Source: org_study_id