A Phase I Trial of Bortezomib and Sunitinib

This study has been completed.
Sponsor:
Collaborators:
Millennium Pharmaceuticals, Inc.
Pfizer
Information provided by (Responsible Party):
John Kauh, Emory University
ClinicalTrials.gov Identifier:
NCT00720148
First received: July 18, 2008
Last updated: January 25, 2012
Last verified: January 2012
  Purpose

The purpose of this study is to test the effect of the combination of sunitinib and bortezomib. We will see what effects it has on your cancer and find the highest dose of each agent that can be given without causing severe side effects.


Condition Intervention Phase
Solid Tumors
Drug: Sunitinib and Bortezomib
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase IB Dose Escalation Study of Bortezomib (VELCADE) Administered Weekly for 4 Weeks and Sunitinib (SU-011248) Administered Daily for 4 Weeks Followed by a 14 Day Rest in Patients With Refractory Solid Tumors

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • Safety and toxicity of combination therapy with sunitinib and bortezomib [ Time Frame: every week ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Tumor shrinkage [ Time Frame: every 6 weeks while on treatment ] [ Designated as safety issue: No ]

Enrollment: 30
Study Start Date: February 2008
Study Completion Date: July 2010
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Sunitinib and Bortezomib
    50 mg/m2, IV (in the vein)on day 5 of each 28 day cycle. Number of cycles: until progression or unacceptable toxicity develops
    Other Names:
    • Sutent
    • Velcade
Detailed Description:

This is a Phase I study assessing the combination of bortezomib and sunitinib in patients with solid tumors that are refractory to standard chemotherapy.

The study will take place in two stages. In both stages, patients will receive sunitinib orally with food once daily for 4 weeks and bortezomib by injection into a vein once a week for 4 weeks. This will be followed by 2 weeks of rest. This 6-week period is called one cycle.

In stage 1, a maximum of 10 patients will be treated sequentially with increasing doses of sunitinib (and a fixed dose of bortezomib). Each dose level must be well tolerated for the next patient to start treatment at the next dose level. Whichever is the highest dose of sunitinib that is well tolerated will then be used for the next stage.

In stage 2, a maximum of 20 patients will be treated sequentially with increasing doses of bortezomib (and a fixed dose of sunitinib). Each dose level must be well tolerated for the next patient to start treatment at the next dose level.

Together, the two stages will determine the highest doses of both sunitinib and bortezomib that are well tolerated when given this combination. Determining these optimal doses is the primary aim of this study. Patients will also be followed to see whether their tumor responds to the treatment.

If a patient's cancer remains stable or improves, they can repeat the treatment cycles. There is no defined end date to this study since patients will be followed for the duration of their survival.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Each patient must meet all of the following inclusion criteria to be enrolled in the study:

  • Refractory advanced solid tumor that has failed standard therapy.
  • ECOG PS ≤ 2
  • Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
  • Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.
  • Male subject agrees to use an acceptable method for contraception for the duration of the study.
  • Cardiac ejection fraction is more than 45%

Exclusion Criteria:

  • Patient has a platelet count of <100 x 109/L within 14 days before enrollment.
  • Patient has an absolute neutrophil count of ANC <1.0 x 109/L within 14 days before enrollment.
  • Patient has a calculated or measured creatinine clearance of <30 mL/minute within 14 days before enrollment.
  • AST, ALT, total bilirubin > twice the upper limits of normal.
  • Received radiation to more than 30% of marrow volume
  • Patient has greater than or equal to Grade 2 peripheral neuropathy within 14 days before enrollment.
  • Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure (see section 8.4), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
  • Patient has hypersensitivity to sunitinib, bortezomib, boron or mannitol.
  • Uncontrolled hypertension
  • History of venous thromboembolic events.
  • Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum Beta-human chorionic gonadotropin (Beta-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
  • Patient has received other investigational drugs with 14 days before enrollment
  • Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
  • Hemorrhagic tendency of the tumor
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00720148

Locations
United States, Georgia
Emory University Winship Cancer Institute
Atlanta, Georgia, United States, 30322
Sponsors and Collaborators
Emory University
Millennium Pharmaceuticals, Inc.
Pfizer
Investigators
Principal Investigator: John Kauh, MD Emory University Winship Cancer Institute
  More Information

No publications provided

Responsible Party: John Kauh, MD, Emory University
ClinicalTrials.gov Identifier: NCT00720148     History of Changes
Other Study ID Numbers: 3549
Study First Received: July 18, 2008
Last Updated: January 25, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Emory University:
Solid tumors

Additional relevant MeSH terms:
Neoplasms
Bortezomib
Sunitinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on July 23, 2014