A Study of Neoadjuvant Sutent for Patients With Renal Cell Carcinoma

Renal Cell Carcinoma Clinical Trial

Official title:

A Phase II, Single Arm, Prospective Study of Neoadjuvant Sutent for Patients With Renal Cell Carcinoma

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00480935
• Other study ID #: 07-0017-C
• Status: Terminated
• Phase: Phase 2
• First received: May 29, 2007
• Last updated: December 7, 2015
• Start date: October 2007
• Est. completion date: October 2011

Study information

• Verified date: December 2015
• Source: University Health Network, Toronto
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial Summary

Study Hypothesis: Patients with local renal cell carcinoma who are treated neoadjuvantly with Sutent may show a radiologic response to the study drug (Sutent).

The study is looking at the neoadjuvant (pre-surgery) administration of Sutent in patients with localized kidney cancer. The purpose of this research is also to evaluate both the safety and effectiveness of Sutent in this patient population.

Description:

Sutent will be given at 50 mg once daily for 4 consecutive weeks followed by a 1 week rest period. The dosage may change during the cycle due to possible drug toxicities. The nephrectomy will then take place following a one-week washout period. After surgery, patients will have follow-up visits at 6 weeks and 3 months. Patients will be followed for 3 years after completions to assess late toxicities, time to progression and progression-free survival.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: October 2011
• Est. primary completion date: October 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically confirmed renal cell carcinoma with a component of clear (conventional) cell histology, which has been assessed with biopsy at screening.

• Locally confined tumour = 7 cm

• Has not undergone nephrectomy and is a candidate for surgical treatment of renal cell carcinoma

• Male or female, 18 years of age or older

• ECOG performance status 0 or 1

• Adequate organ function as defined by the following criteria:

• Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase [SGOT]) and serum alanine transaminase (ALT; serum glutamic pyruvic transaminase [SGPT]) less than or equal to 2.5 x central laboratory upper limit of normal (CL-ULN), or AST and ALT less than or equal to 5 x CL ULN if liver function abnormalities are due to underlying malignancy

• Total serum bilirubin less than or equal to 1.5 x CL-ULN

• Absolute neutrophil count (ANC) greater than or equal to 1500/mL

• Platelets greater than or equal to 100,000/mL

• Hemoglobin greater than or equal to 9.0 g/dL

• Serum calcium less than or equal to 12.0 mg/dL

• Serum creatinine less than or equal to 1.5 x CL-ULN

• Prothrombin time (PT) less than or equal to 1.5 x CL-ULN

• Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to enrollment

• Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures

Exclusion Criteria:

• Prior therapy of any kind for RCC (including nephrectomy, immunotherapy, chemotherapy, radiation, hormonal, or investigational therapy)

• Abnormal ECG- including long QT/QTc interval, AV block or arrythmia

• Tumour associated with local extension into adjacent tissues

• Tumour associated with renal/vena caval thrombus

• Tumour associated with lymphadenopathy (lymph node > 1 cm)

• Evidence of rapidly progressive disease or other factors requiring surgery to take place before the 12 weeks scheduled for neoadjuvant treatment

• Major surgery within 4 weeks of commencing study treatment

• Any toxicity with a NCI CTCAE grade 3 or 4

• Diagnosis of any second malignancy within the last 5 years, except for adequately treated basal cell carcinoma, squamous cell skin cancer, or in situ cervical cancer

• Evidence of metastatic renal cell carcinoma

• Any of the following within the 12 months prior to study drug administration:

myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism

• Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication

• Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness

• Current treatment on another clinical trial

• Pregnancy or breastfeeding

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Renal Cell Carcinoma

Intervention

Drug:
• Sunitinib Malate (Sutent)
Sutent will be given at 50 mg once daily for 4 consecutive weeks followed by a 1 week washout period. The dosage may change during the cycle due to possible drug toxicities. The nephrectomy will then take place following a one-week washout period.

Locations

Country	Name	City	State
Canada	University Health Network, Princess Margaret Hospital	Toronto	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
University Health Network, Toronto	Pfizer

Country where clinical trial is conducted

Canada, 

References & Publications (5)

Lamuraglia M, Escudier B, Chami L, Schwartz B, Leclère J, Roche A, Lassau N. To predict progression-free survival and overall survival in metastatic renal cancer treated with sorafenib: pilot study using dynamic contrast-enhanced Doppler ultrasound. Eur J Cancer. 2006 Oct;42(15):2472-9. Epub 2006 Sep 11. Erratum in: Eur J Cancer. 2007 May;43(8):1336. — View Citation

Marzola P, Degrassi A, Calderan L, Farace P, Nicolato E, Crescimanno C, Sandri M, Giusti A, Pesenti E, Terron A, Sbarbati A, Osculati F. Early antiangiogenic activity of SU11248 evaluated in vivo by dynamic contrast-enhanced magnetic resonance imaging in an experimental model of colon carcinoma. Clin Cancer Res. 2005 Aug 15;11(16):5827-32. — View Citation

Mickisch GH, Garin A, van Poppel H, de Prijck L, Sylvester R; European Organisation for Research and Treatment of Cancer (EORTC) Genitourinary Group. Radical nephrectomy plus interferon-alfa-based immunotherapy compared with interferon alfa alone in metastatic renal-cell carcinoma: a randomised trial. Lancet. 2001 Sep 22;358(9286):966-70. — View Citation

Motzer RJ, Rini BI, Bukowski RM, Curti BD, George DJ, Hudes GR, Redman BG, Margolin KA, Merchan JR, Wilding G, Ginsberg MS, Bacik J, Kim ST, Baum CM, Michaelson MD. Sunitinib in patients with metastatic renal cell carcinoma. JAMA. 2006 Jun 7;295(21):2516-24. — View Citation

Volpe A, Panzarella T, Rendon RA, Haider MA, Kondylis FI, Jewett MA. The natural history of incidentally detected small renal masses. Cancer. 2004 Feb 15;100(4):738-45. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To assess the radiologic response rate associated with 1 cycle of Sutent for neoadjuvant treatment of patients with renal cell carcinoma		5 weeks	No
Secondary	To assess the change in tumour vascularity in response to 1 cycle of neoadjuvant treatment of patients with renal cell carcinoma		5 weeks	No
Secondary	To assess the change in expression of the following tissue markers; PDGF-alpha, PDGF-Beta, Flt-3, VEGFR and c-KIT, as compared to pre-treatment biopsy tissue as well as to stage, gender and age-matched controls		5 weeks	No
Secondary	To evaluate the safety and tolerability of Sutent given preoperatively		5 weeks	Yes
Secondary	To assess late toxicities, time to progression, progression free survival, and survival		5 weeks - 3 years	Yes
Secondary	A DNA microarray will be used for gene expression profiling of the tissue harvested at biopsy and surgery to investigate differential expression profiles and their association with Sutent sensitivity or resistance		5 weeks	No