Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01030783
Other study ID # AV-951-09-301
Secondary ID
Status Completed
Phase Phase 3
First received
Last updated
Start date December 2009
Est. completion date June 2013

Study information

Verified date October 2019
Source AVEO Pharmaceuticals, Inc.
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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).


Recruitment information / eligibility

Status Completed
Enrollment 517
Est. completion date June 2013
Est. primary completion date July 2012
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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.)

Study Design


Intervention

Drug:
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.
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.

Locations

Country Name City State
Argentina Site 102 Sante Fe
Bulgaria Site 403 Plovdiv
Bulgaria Site 400 Sofia
Bulgaria Site 404 Sofia
Bulgaria Site 401 Varna
Bulgaria Site 402 Veliko Tarnovo
Canada Site 110 Montréal Quebec
Chile Site 121 La Reina Santiago De Chile
Chile Site 122 Santiago
Chile Site 123 Temuco
Czechia Site 411 Prague 8
France Site 130 Marseille
France Site 133 Saint Herblain Cedex
Hungary Site 423 Budapest
Hungary Site 421 Kaposvár
Hungary Site 422 Pécs
Hungary Site 424 Szombathely
India Site 156 Ahmedabad Gujarat
India Site 154 Delhi
India Site 157 Hyderabad Andhra Pradesh
India Site 155 Jaipur Rajasthan
India Site 191 Jaipur Rajasthan
India Site 150 Kolkata West Bengal
India Site 158 Lucknow Uttar Pradesh
India Site 151 Nashik Maharashtra
India Site 190 Patna Bihar
India Site 153 Pune Maharashtra
India Site 159 Pune Maharashtra
India Site 152 Vellore Tamil Nadu
Italy Site 160 Arezzo
Italy Site 161 Pavia
Italy Site 162 Roma
Poland 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
Romania Site 444 Brasov
Romania Site 440 Bucharest
Romania Site 441 Bucharest
Romania Site 443 Bucharest
Romania Site 442 Timisoara
Russian Federation Site 451 Chelyabinsk
Russian Federation Site 455 Ekaterinburg
Russian Federation Site 468 Ioshkar Ola
Russian Federation Site 452 Kazan
Russian Federation Site 453 Moscow
Russian Federation Site 454 Moscow
Russian Federation Site 458 Moscow
Russian Federation Site 460 Moscow
Russian Federation Site 461 Moscow
Russian Federation Site 462 Moscow
Russian Federation Site 450 Nizhny Novgorod
Russian Federation Site 456 Obninsk
Russian Federation Site 467 Omsk
Russian Federation Site 463 Pyatigorsk
Russian Federation Site 457 Rostov-on-Don
Russian Federation Site 465 St. Petersburg
Russian Federation Site 466 St. Petersburg
Russian Federation Site 459 Ufa Republic Of Bashkortostan
Russian Federation Site 464 Yaroslavi
Serbia Site 480 Belgrade
Serbia Site 481 Belgrade
Serbia Site 482 Belgrade
Serbia Site 483 Nis
Serbia Site 484 Sremska Kamenica
Ukraine 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
United Kingdom Site 170 Cambridge
United Kingdom Site 173 Ipswich
United Kingdom Site 172 Leicester
United States Site 187 Dallas Texas
United States Site 180 Gainesville Florida
United States Site 185 Los Angeles California
United States Site 182 Minneapolis Minnesota
United States Site 186 New York New York
United States Site 184 Orlando Florida

Sponsors (1)

Lead Sponsor Collaborator
AVEO Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Bulgaria,  Canada,  Chile,  Czechia,  France,  Hungary,  India,  Italy,  Poland,  Romania,  Russian Federation,  Serbia,  Ukraine,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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 Overall Survival (OS) of Subjects Randomized to Treatment With Tivozanib or Sorafenib Overall survival (OS) is defined as the time from the date of randomization to date of death due to any cause. In the absence of confirmation of death, survival time will be censored at the last date the subject is known to be alive. Subjects lacking data beyond randomization will have their survival times censored on the date of randomization. Date of randomization to date of death
Secondary Objective Response Rate (ORR) of Subjects Randomized to Treatment With Tivozanib or Sorafenib Objective response rate (ORR) is defined as the percentage of subjects who have at least a 30% reduction in the sum of diameters per RECIST (Version 1.0). Every 8 weeks from date of randomization until disease progression
Secondary Duration of Response (DR) of Subjects Randomized to Treatment With Tivozanib or Sorafenib Duration of response (DR) is defined as the time from the first documentation of objective tumor response to the first documentation of tumor progression per RECIST 1.0 or to death due to any cause. Assessed every 8 weeks from date of randomization until date of progression
Secondary Safety and Tolerability of Tivozanib and Sorafenib Dose reductions and interruptions were allowed for subjects taking tivozanib or sorafenib. Any modification of study drug administration, and the reason for such action, was clearly noted on the subject's eCRF. From start of treatment therapy to completion of treatment therapy, an average of 11 months
Secondary To Compare Kidney-specific Symptoms and Health Outcome Measurements in Subjects Randomized to Treatment With Tivozanib or Sorafenib The Disease Related Symptom Scale of the Functional Assessment of Cancer Therapy - Advanced Kidney Cancer Symptom Index (FKSI-DRS) measured kidney specific symptoms on a 0-36 scale, with lower scores corresponding to worse overall QOL and higher scores corresponding to better overall QOL. The Functional Assessment of Cancer Therapy-General (FACT-G) measured general wellbeing scored on a 0-108 scale, with lower scores corresponding to worse overall QOL and higher scores corresponding to better overall QOL. The European Quality of Life-5 Dimensions (EQ-5D) measured patient health related quality of life scored on a 0-1 scale, with 0 being worse health state and 1 being perfect health state. The European Quality of Life-5 Dimensions Visual Analog Scales (EQ-5D VAS) measured patient health related quality of life on a visual analog scale from 0 to 100, with 0 being the worst and 100 being the best. These scales were self-administered by patients at the start of the visit. At Day 1 of each 28 day cycle throughout the course of the study, for an average of 11 months per subject
Secondary Pharmacokinetics (Serum Concentrations) of Tivozanib Samples for tivozanib serum concentrations will be collected at the following time points: Cycle 1, Day 1 (prior to dosing), Cycle 1, Day 15 (prior to dosing), Cycle 2, Day 1 (prior to dosing), and Cycle 2, Day 22-28. The serum concentrations of tivozanib were tabulated for individual subjects and summarized by nominal time using standard descriptive statistics (concentrations presented in ng/mL). Cycle 1, Day 1 (prior to dosing), Cycle 1, Day 15 (prior to dosing), Cycle 2, Day 1 (prior to dosing), and Cycle 2, Day 22-28
See also
  Status Clinical Trial Phase
Recruiting NCT05361434 - A Study of the Effectiveness of Cabozantinib in Combination With Nivolumab as First-line Treatment of Advanced Renal Cell Carcinoma (aRCC) in Adults
Recruiting NCT05928806 - Advanced Renal Cell Cancer Combination ImmunoThErapy Clinical Trial Phase 2
Recruiting NCT03647878 - Study of Cabozantinib as Monotherapy or in Combination With Nivolumab in Patients With Advanced or Metastatic Renal Cell Carcinoma Under Real-life Clinical Setting in 1st Line Treatment.
Completed NCT00197860 - Dendritic Cell Based Therapy of Renal Cell Carcinoma Phase 1/Phase 2
Completed NCT05444933 - A Study to Collect Pre-existing Data on the Administration of Cabozantinib in Participants With Advanced Renal Cell Carcinoma (aRCC) Who Initiated Cabozantinib in 2nd Line in a Real-life Clinical Setting in France.
Recruiting NCT05522231 - Efficacy and Safety of Fruquintinib in Combination With Sintilimab in Advanced Renal Cell Carcinoma (FRUSICA-2) Phase 2/Phase 3
Recruiting NCT05119335 - A Study of NKT2152, a HIF2α Inhibitor, in Patients With Advanced Clear Cell Renal Cell Carcinoma Phase 1/Phase 2
Recruiting NCT05641545 - IVAC-RCC-001: A Personalized Neoantigen Vaccine as Add-on to Standard of Care Checkpoint Inhibitor in Advanced/Metastatic RCC Patients Phase 1
Active, not recruiting NCT02231749 - Nivolumab Combined With Ipilimumab Versus Sunitinib in Previously Untreated Advanced or Metastatic Renal Cell Carcinoma (CheckMate 214) Phase 3
Active, not recruiting NCT04514484 - Testing the Combination of the Anti-cancer Drugs XL184 (Cabozantinib) and Nivolumab in Patients With Advanced Cancer and HIV Phase 1
Terminated NCT01582672 - Phase 3 Trial of Autologous Dendritic Cell Immunotherapy Plus Standard Treatment of Advanced Renal Cell Carcinoma Phase 3
Completed NCT03200717 - Study of Efficacy, Safety, and Quality of Life of Pazopanib in Patients With Advanced and/or Metastatic Renal Cell Carcinoma After Prior Checkpoint Inhibitor Treatment Phase 2
Active, not recruiting NCT05122546 - CBM588 in Combination With Nivolumab and Cabozantinib for the Treatment of Advanced or Metastatic Kidney Cancer Phase 1
Completed NCT00853372 - AMG 386 Phase 2 Open-Label Renal Cell Carcinoma (RCC) Study 1st Line or After Cytokine Failure in Combination With Sunitinib Phase 2
Active, not recruiting NCT02735252 - PROMOTE: Identifying Predictive Markers of Response for Genitourinary Cancer N/A
Recruiting NCT05868174 - Combination of 177Lu-TLX250 and Peposertib in Patients With Carbonic Anhydrase IX -Expressing Solid Tumors Phase 1
Completed NCT00467025 - AMG 386, 20060159 Phase 2, RCC 1st Line in Combination With Sorafenib Phase 2
Active, not recruiting NCT03829111 - CBM588, Nivolumab, and Ipilimumab in Treating Patients With Stage IV or Advanced Kidney Cancer Phase 1
Recruiting NCT05703854 - Study of CAR.70-engineered IL15-transduced Cord Blood-derived NK Cells in Conjunction With Lymphodepleting Chemotherapy for the Management of Advanced Renal Cell Carcinoma, Mesothelioma and Osteosarcoma Phase 1/Phase 2
Completed NCT01076010 - An Extension Treatment Protocol for Subjects Who Have Participated in a Study of Tivozanib Versus Sorafenib in Kidney Carcinoma (Protocol AV-951-09-301). Phase 3

External Links