Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Phase II Study of Alternating Sunitinib and Temsirolimus

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Dartmouth-Hitchcock Medical Center
Sponsor:
Information provided by (Responsible Party):
Marc S. Ernstoff, Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier:
NCT01517243
First received: January 17, 2012
Last updated: March 27, 2014
Last verified: March 2014
  Purpose

In the past 5 years, treatment for metastatic Renal Cell Carcinoma (mRCC) has focused on agents directed at blocking tumor and vascular growth pathways. Sunitinib blocks the vascular endothelial growth factor receptor (VEGFr) and temsirolimus is an inhibitor of mammalian target of rapamycin (mTOR). Both sunitinib and temsirolimus are FDA approved agents for mRCC. When agents like these are given together, the toxicity increases but they can be given safely, at full doses, sequentially. We hypothesize that alternating these agents will double the progression free survival (PFS) of the agents when given sequentially.


Condition Intervention Phase
Metastatic Renal Cell Carcinoma
Drug: Sunitinib
Drug: Temsirolimus
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Alternating Targeted Therapy in Patients With Metastatic Renal Cell Carcinoma: A Phase II Study of Alternating Sunitinib and Temsirolimus

Resource links provided by NLM:


Further study details as provided by Dartmouth-Hitchcock Medical Center:

Primary Outcome Measures:
  • Time to Progression [ Time Frame: From the date of randomization until the first documented progression or date of death from any cause. ] [ Designated as safety issue: No ]
    To determine the time to progression in metastatic renal cell carcinoma patients treated with alternating targeted therapy


Secondary Outcome Measures:
  • Clinical Response Rate [ Time Frame: Every 12 weeks until progression, estimated time frame is 18 months ] [ Designated as safety issue: No ]
    To be assigned a status of partial response or complete response, changes in tumor measurements must be confirmed by repeat assessments that should be performed no less than 4 weeks after the criteria for response are first met. In the case of stable disease, follow-up measurements must have met the stable disease criteria at least once after study entry at a minimum interval (in general, not less than 6-8 weeks) that is defined in the study protocol.


Estimated Enrollment: 37
Study Start Date: June 2010
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Alternating Sunitinib and Temsirolimus

A cycle is defined as:

Sunitinib 50mg by mouth daily for 4 weeks followed by a two week rest Temsirolimus 25mg IV weekly for 4 weeks followed by a two week rest

Drug: Sunitinib
Sunitinib 50mg by mouth daily for 4 weeks followed by a two week rest
Other Name: Sutent
Drug: Temsirolimus
Temsirolimus 25mg IV weekly for 4 weeks followed by a two week rest
Other Name: TORISEL®

Detailed Description:

SUMMARY: Alternating Targeted Therapy in Patients with Metastatic Renal Cell Carcinoma: A Phase II Study of Alternating Sunitinib and Temsirolimus

Patients with measurable metastatic renal cell carcinoma (any histology) are eligible. All patients will be treated as outlined below with sunitinib alternating with temsirolimus.

Patients will be treated continuously, until evidence of progression of disease, or for up to two cycles following disappearance of all disease.

A cycle is defined as:

Sunitinib 50mg by mouth daily for 4 weeks followed by a two week rest Temsirolimus 25mg IV weekly for 4 weeks followed by a two week rest

  Eligibility

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

Inclusion Criteria

  • Histologically confirmed metastatic renal cell cancer with evaluable disease.
  • Patients must be at least 2 weeks from their last immunotherapy, surgery or chemotherapy (6 weeks for nitrosureas) and recovered from all ill effects.
  • Karnofsky Performance Status ≥60%
  • Life expectancy ≥ twelve weeks
  • Adequate end organ function:

Cardiac Left ventricular ejection fraction (LVEF) ≥lower limit of institutional normal (LLN) as assessed by echocardiography (ECHO) . The same modality used at baseline must be applied for subsequent evaluations.

  • Women should not be lactating and, if of childbearing age, have a negative pregnancy test within two weeks of entry to the study and practicing acceptable forms of birth control
  • Appropriate Contraception in both sexes
  • The patient must be competent and signed informed consent.

EXCLUSION CRITERIA

  • Concomitant second malignancy except for non-melanoma skin cancer, and non-invasive cancer such as cervical CIS, superficial bladder cancer without local recurrence, breast CIS.
  • In patients with a prior history of invasive malignancy, less than five years in complete remission.
  • Have evidence of significant co-morbid illness such as uncontrolled diabetes, hypertension or active infection that would preclude treatment on this regimen.
  • Prior treatment with either sunitinib or temsirolimus
  • Clinically significant gastrointestinal abnormalities
  • Presence of uncontrolled infection.
  • Prolongation of corrected QT interval (QTc) > 480 milliseconds - History of any one or more of the following cardiovascular conditions within the past 12 months:

    1. Cardiac angioplasty or stenting
    2. Myocardial infarction
    3. Unstable angina
    4. Coronary artery by-pass graft surgery
    5. Symptomatic peripheral vascular disease
    6. Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA)
  • History of cerebrovascular accident (CVA) including transient ischemic attack (TIA) within the past 12 months.
  • History of pulmonary embolism or untreated deep venous thrombosis (DVT)within the past 6 months. Note: Subjects with recent DVT who have been treated with therapeutic anticoagulating agents for at least 6 weeks are eligible.
  • Poorly controlled hypertension [defined as systolic blood pressure (SBP) of

    ≥150 or diastolic blood pressure (DBP) of ≥ 90. Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry.

  • Prior major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer.
  • Evidence of active bleeding or bleeding diathesis
  • Hemoptysis within 6 weeks of first dose of study drug.
  • Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels
  • Any serious and/or unstable pre-existing medical, psychiatric, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance to the study.
  • Is now undergoing and/or has undergone in the 14 days immediately prior to first dose of study drug any minor surgeries (i.e. skin biopsy, tooth extraction, etc.) and recovered from all ill effects.
  • Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1 and/or that is progressing in severity.
  • Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to sunitinib or temsirolimus.
  • Untreated brain metastasis. (Brain metastases that are stable based on radiographic evidence 4 weeks after radiation and/or surgery are permitted).
  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: NCT01517243

Contacts
Contact: Eryn M. Bagley, CCRC 603-650-4035 eryn.m.bagley@hitchcock.org

Locations
United States, New Hampshire
Dartmouth-Hitchcock Medical Center Recruiting
Lebanon, New Hampshire, United States, 03756
Principal Investigator: Marc S. Ernstoff, MD         
United States, Vermont
University of Vermont, Vermont Cancer Center Recruiting
Burlington, Vermont, United States, 05401
Contact: Debbie McAdoo    802-656-9113      
Principal Investigator: Steven Ades, MD         
Sponsors and Collaborators
Dartmouth-Hitchcock Medical Center
Investigators
Principal Investigator: Marc S Ernstoff, MD Dartmouth-Hitchcock Medical Center
  More Information

Additional Information:
No publications provided

Responsible Party: Marc S. Ernstoff, Associate Director for Clinical Research, Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier: NCT01517243     History of Changes
Other Study ID Numbers: D1011
Study First Received: January 17, 2012
Last Updated: March 27, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Dartmouth-Hitchcock Medical Center:
Metastatic Renal Cell Carcinoma
sunitinib
alternating
temsirolimus

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Adenocarcinoma
Kidney Diseases
Kidney Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Urogenital Neoplasms
Urologic Diseases
Urologic Neoplasms
Everolimus
Sirolimus
Sunitinib
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014