Clinical trial NCT01517243: Phase II Study of Alternating Sunitinib and Temsirolimus
Official title: Alternating Targeted Therapy in Patients With Metastatic Renal Cell Carcinoma: A Phase II Study of Alternating Sunitinib and Temsirolimus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Renal Cell Carcinoma
Keywords: Metastatic Renal Cell Carcinoma
sunitinib
alternating
temsirolimus
Lead sponsor: Dartmouth-Hitchcock Medical Center
Sponsor class: OTHER
First posted: 2012-01-25
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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 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).

Primary outcomes:
measure: Progression Free Survival
timeFrame: 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:
measure: Clinical Response Rate as Measured by Best Response Achieved
timeFrame: Every 12 weeks from randomization until progression, estimated time frame is 18 months
measure: To Characterize the Toxicity Profile
timeFrame: Throughout the duration of the patient remaining on study treatment which was a median time of 8 months
Other outcomes:
Locations:
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Burlington
country: United States
facility: University of Vermont, Vermont Cancer Center
state: Vermont
Study officials:
affiliation: Dartmouth-Hitchcock Medical Center
name: Lionel D Lewis, MD
role: PRINCIPAL_INVESTIGATOR
References: