Phase II Study of Alternating Sunitinib and Temsirolimus

NCT01517243 | Completed Phase 2 Results DMC

• 1 other identifier: D1011
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Metastatic Renal Cell Carcinoma

Keywords

Metastatic Renal Cell Carcinoma; sunitinib; alternating; temsirolimus

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  To determine the time to disease progression in metastatic renal cell carcinoma patients treated with alternating targeted therapy. This time interval constitutes the metric progression free survival time.

  From the date of randomization until the first documented disease progression or date of death from any cause, evaluated every 12 weeks throughout duration of study treatment

Secondary Outcomes (2)

• Clinical Response Rate as Measured by Best Response Achieved

  Every 12 weeks from randomization until progression, estimated time frame is 18 months

• To Characterize the Toxicity Profile

  Throughout the duration of the patient remaining on study treatment which was a median time of 8 months

Study Arms (1)

Alternating Sunitinib and Temsirolimus

EXPERIMENTAL

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; Drug: Temsirolimus

Interventions

Sunitinib DRUG

Sunitinib 50mg by mouth daily for 4 weeks followed by a two week rest

Also known as: Sutent

Alternating Sunitinib and Temsirolimus

Temsirolimus DRUG

Temsirolimus 25mg IV weekly for 4 weeks followed by a two week rest

Also known as: TORISEL®

Alternating Sunitinib and Temsirolimus

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• Cardiac angioplasty or stenting
• Myocardial infarction
• Unstable angina
• Coronary artery by-pass graft surgery
• Symptomatic peripheral vascular disease
• 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.

Sponsors & Collaborators

• Dartmouth-Hitchcock Medical Center: lead

Study Sites (2)

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

University of Vermont, Vermont Cancer Center

Burlington, Vermont, 05401, United States

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Sunitinib; temsirolimus

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Lionel Lewis
• Organization: Dartmouth College

lionel.d.lewis@dartmouth.edu

1-603-650-8685

Study Officials

• Lionel D Lewis, MD

  Dartmouth-Hitchcock Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Director of the Dartmouth Clinical Trials Office

Study Record Dates

• First Submitted: January 17, 2012
• First Posted: January 25, 2012
• Study Start: September 22, 2010
• Primary Completion: August 20, 2018
• Study Completion: August 20, 2018
• Last Updated: September 21, 2023
• Results First Posted: September 21, 2023

Record last verified: 2023-07

Locations

US (2)