Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00788060
Other study ID # Pro00000548
Secondary ID
Status Completed
Phase Phase 1
First received November 6, 2008
Last updated February 12, 2015
Start date October 2008
Est. completion date December 2012

Study information

Verified date February 2015
Source Duke University
Contact n/a
Is FDA regulated No
Health authority United States: Food and Drug AdministrationUnited States: Institutional Review Board
Study type Interventional

Clinical Trial Summary

This is a single center, Phase Ib study of Sunitinib and RAD001 in patients with advanced RCC. The study design is a phase I interpatient dose-escalation with a dose expansion at the maximum tolerated dose (MTD) in patients with metastatic RCC . In the dose escalation portion, patients will be treated with sunitinib, given in an intermittent schedule (2 weeks of daily dosing followed by one week off drug. RAD001 will be given daily. Escalation of both drugs will occur as tolerated. Treatment will be arbitrarily divided into 3-week cycles, with dose limiting toxicity (DLT) determined by Cycle 2 Day 0.


Description:

Escalation of both drugs will occur as tolerated. Treatment will be arbitrarily divided into 3-week cycles, with dose limiting toxicity (DLT) determined by Cycle 2 Day 0. Dose levels will be evaluated one at a time beginning with 3 patients. If 1/3 patients demonstrate DLT (as defined in section Complete), then enrollment will proceed to the next dose level. 1/3 patients develops a DLT, then 3 more patients will be accrued to this dose level. If 0-1/6 patients demonstrate DLT, then enrollment will proceed to the next dose level. However, if 2 or more patients out of 6 demonstrate DLT at a dose level, then enrollment will proceed at the next lowest dose level. The highest dose level not resulting in greater than 1/6 DLT will be considered the MTD. Dose expansion will then proceed at this dose level.

Once the maximum tolerated dose has been established for this regimen a dose expansion of 20 patients with metastatic RCC will be undertaken. Up to 10 patients with a positive FDG- PET scan at baseline (defined by 1 or more target lesions demonstrating an SUV > 5.0) will begin treatment per Figure 2B. Patients 1-10 will begin Sunitinib on Day 0 and begin RAD001 on Day 14 after repeat FDG-PET scan. Patients 11-20, will have a 2 week lead-in period of RAD001 and will begin Sunitinib 2 weeks later on Day 0. After repeat FDG-PET scan. Both groups of patients will repeat PET scan at Day 14 of cycle 2. Patients with negative FDG PET scans (SUV < 5.0 in all lesions) will not undergo repeat scanning. Patients will undergo evaluations for tumor response every 12 weeks with appropriate measurement studies (CT, MRI, bone scan). In the setting of a mixed response (progressive disease in 1 or more lesions but continued regression or stable disease below baseline in other lesions) patients may continue on study if it is determined by the PI, treating physician and patient that there is ongoing clinical benefit to the patient.


Recruitment information / eligibility

Status Completed
Enrollment 5
Est. completion date December 2012
Est. primary completion date December 2012
Accepts healthy volunteers No
Gender Both
Age group 18 Years and older
Eligibility Inclusion Criteria:

Patients will be eligible for inclusion in this study only if all of the following criteria apply:

- Patients must have histologically confirmed diagnosis of RCC.

- Patients must have undergone a nephrectomy

- Clinical or radiographic evidence of metastatic disease.

- A minimum of 4 weeks from full field radiation therapy, surgery, chemotherapy or other investigational agent. Treatment may begin one week following limited field radiation therapy.

- Subjects who have received prior limited field radiotherapy, biologic/immunotherapy or surgery must have a documented recovery period > 2 weeks

- Patients must have normal organ and marrow function as defined below:

hemoglobin > 9.0g/dL absolute neutrophil count > 1,500/µl platelets > 100,000/µl total bilirubin < 1.5 X upper limit of normal (ULN) AST(SGOT)/ALT(SGPT) < 2.5 X ULN creatinine < 1.5 X ULN (or 24 hour measured creatinine clearance > 40 mL/min) total fasting cholesterol < 350 total triglycerides < 300

- Age > 18 years.

- ECOG score of 0-2 (See Appendix 11.1).

- For patients with diabetes a Hgb A1C of = 8

- Subject agrees to use a medically acceptable form of birth control during and for at least 3 months after completion of the study treatment, if he/she is sexually active

- Women of childbearing potential must have a negative serum pregnancy test within 3 days prior to treatment

- Ability to swallow and retain oral medication.

- Ability to understand and the willingness to sign a written informed consent document.

- Written informed consent obtained according to local guidelines

Exclusion Criteria:

A patient will not be eligible for inclusion in this study if any of the following criteria apply:

- History of solid organ or stem cell transplantation. Also, no current use of chronic immunosuppressive therapy is allowed.

- Patients with active brain metastases (or history of brain metastases) should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.

- History of HIV, hepatitis B, or hepatitis C infection.

- Patients who have received investigational, biologic, hormonal (other than ADT), immunotherapy, or chemotherapy less than 4 weeks prior to entry on this study or have not recovered from the toxic effects of such therapy.

- Patients who have experienced severe trauma or undergone major surgery within 4 weeks prior to entry on this study or have not recovered to grade 1 or less may not participate.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (requiring antifungal, antibiotic or antiviral therapy), symptomatic congestive heart failure (NYHC II or greater), unstable angina pectoris, cardiac arrhythmia (uncontrolled SVT or any VT), uncontrolled diabetes or psychiatric illness/social situations that would limit compliance with study requirements.

- Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001 (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection).

- Patients who have received prior treatment with an mTOR inhibitor.

- Patients who have received prior treatment with Sunitinib are not eligible to participate in this study.

Study Design

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


Related Conditions & MeSH terms


Intervention

Drug:
Everolimus (RAD001)
5mg per day, continuously
Sunitinib (Sutent)
37.5 mg per day, 14 days on, 7 day break

Locations

Country Name City State
United States Duke University Medical Center Durham North Carolina

Sponsors (3)

Lead Sponsor Collaborator
Daniel George, MD Novartis, Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary To determine the maximum tolerated dose (MTD)/recommended Phase 2 regimen of 2+1 dosing with Sunitinib and daily RAD001 in patients with advanced renal cell carcinoma. 1 year Yes
Primary To determine the safety and tolerability of 2+1 dosing of Sunitinib and daily RAD001 in patients with advanced RCC 1 year Yes
Primary To more fully evaluate the safety and tolerability of 2+1 dosing of Sunitinib and daily RAD001 at the MTD/recommended Phase 2 dose in patients with advanced RCC 1 year Yes
Secondary Describe the non-dose limiting toxicities associated with combination therapy using 2+1 dosing Sunitinib and daily RAD001. 1 year Yes
Secondary Describe the pharmacokinetics of Sunitinib and RAD001 and evaluate any association with disease response 1 year No
Secondary To estimate objective response rate (partial or complete) seen in patients with advanced RCC in a dose expansion cohort treated at the MTD or recommended Phase 2 dose regimen 1 year No
Secondary To estimate the overall survival of RCC patients treated with Sunitinib and RAD001 1 year No
Secondary To estimate the time to disease progression of RCC patients treated with Sunitinib and RAD001 1 year No
See also
  Status Clinical Trial Phase
Active, not recruiting NCT04987203 - Study to Compare Tivozanib in Combination With Nivolumab to Tivozanib Monotherapy in Subjects With Renal Cell Carcinoma Phase 3
Recruiting NCT06391879 - Establishment of a Multidimensional Prediction Model for the Natural Course of VHL Disease-related Renal Cell Carcinoma
Completed NCT02526017 - Study of Cabiralizumab in Combination With Nivolumab in Patients With Selected Advanced Cancers Phase 1
Recruiting NCT05059444 - ORACLE: Observation of ResiduAl Cancer With Liquid Biopsy Evaluation
Terminated NCT03655613 - APL-501 or Nivolumab in Combination With APL-101 in Locally Advanced or Metastatic HCC and RCC Phase 1/Phase 2
Active, not recruiting NCT03170960 - Study of Cabozantinib in Combination With Atezolizumab to Subjects With Locally Advanced or Metastatic Solid Tumors Phase 1/Phase 2
Withdrawn NCT05418387 - A Social Support Intervention to Improve Treatment Among Hispanic Kidney and Liver Cancer Patients in Arizona N/A
Recruiting NCT04623502 - An Investigation of Kidney and Urothelial Tumor Metabolism in Patients Undergoing Surgical Resection and/or Biopsy N/A
Completed NCT02853344 - Study of Pembrolizumab (MK-3475) Monotherapy in Locally Advanced/Metastatic Renal Cell Carcinoma (MK-3475-427/KEYNOTE-427) Phase 2
Terminated NCT04088500 - A Study of Combination Nivolumab and Ipilimumab Retreatment in Patients With Advanced Renal Cell Carcinoma Phase 2
Completed NCT05070637 - Circulating Tumor Cell Reducing No-touch Nephrectomy N/A
Active, not recruiting NCT03634540 - A Trial of Belzutifan (PT2977, MK-6482) in Combination With Cabozantinib in Patients With Clear Cell Renal Cell Carcinoma (ccRCC) (MK-6482-003) Phase 2
Not yet recruiting NCT06049030 - A Study of HS-10516 in Patients With Advanced Clear Cell Renal Cell Carcinoma Phase 1
Completed NCT03652077 - A Safety and Tolerability Study of INCAGN02390 in Select Advanced Malignancies Phase 1
Completed NCT01358721 - Phase I Biomarker Study (BMS-936558) Phase 1
Active, not recruiting NCT04503148 - Anesthesia and Cancer Study: Renal Cell Carcinoma N/A
Completed NCT02386826 - INC280 Combined With Bevacizumab in Patients With Glioblastoma Multiforme Phase 1
Not yet recruiting NCT05808608 - A Study of AK104 Plus Axitinib in Advanced/Metastatic Special Pathological Subtypes of Renal Cell Carcinoma Phase 1/Phase 2
Withdrawn NCT03323710 - Study of Propranolol Plus Sunitinib in First-line Treatment of Metastatic Renal Cell Carcinoma Phase 2
Completed NCT03052504 - Prospective Versus Retrospective Complications in Radical Cystectomy and Nephrectomy