Clear Cell Renal Cell Carcinoma
Conditions
Keywords
Recurrent clear cell renal cell carcinoma, Bevacizumab, Erlotinib, Imatinib
Brief summary
This phase I/II trial will evaluate the bevacizumab/erlotinib combination with the addition of imatinib (Gleevec). The combined inhibition greatly enhances the anti-tumor effects. Although the safety of the bevacizumab/erlotinib/imatinib combination has not yet been demonstrated, the mild to moderate side effects of all of these agents are not predicted to cause prohibitive toxicity. A brief phase I portion will be included in this trial, to optimize doses of the 3 agents prior to proceeding with the phase II trial.
Detailed description
Upon determination of eligibility, patients will be receive: Bevacizumab + Erlotinib + Imatinib A brief phase I dose escalation study will be performed to define the imatinib dose that will be used.
Interventions
DRUGBevacizumab
10mg/kg IV infusion every 2 weeks
DRUGErlotinib
150 mg po daily
DRUGImatinib
400-600mg daily
Sponsors
Genentech, Inc.
Novartis
SCRI Development Innovations, LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
To be included in this study, you must meet the following criteria: * Metastatic or unresectable clear cell renal carcinoma confirmed by biopsy * Previous nephrectomy is required * Maximum of 1 previous systemic regimen for metastatic disease. * Able to perform activities of daily living with minimal assistance * Measurable disease * Adequate bone marrow, liver and kidney * Written informed consent.
Exclusion criteria
* Age \< 18 years * Treatment with more than 1 previous systemic regimen * History of heart attack within 6 months * Clinically significant cardiovascular disease * Moderate to severe vascular disease. * Active brain metastases. * History or evidence by physical examination of brain tumor * Seizures not controlled with standard medical therapy * history of stroke or other serious disorders of the nervous system * Clinical history of coughing or vomiting blood within the past 3 months. * PEG tubes or G tubes * Chronic therapy with NSAIDS or other platelet inhibitors * Proteinuria * Nonhealing wound, ulcer, or long bone fracture * Clinical evidence or history of a bleeding disorder * Requiring full dose anticoagulation with coumadin * Receiving chronic steroid therapy * Significant medical conditions. * Tumors other than clear cell * History of stroke within 6 months. * History of abdominal fistula,perforation,or abscess within 6 months. Please note: There are additional inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment | 18 months | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. |
| Progression Free Survival (PFS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Worsening of Their Disease | 18 months | — |
| Overall Survival (OS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death | 24 months | — |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bevacizumab/Erlotinib/Imatinib In the phase I portion: Bevacizumab 10 mg/kg slow IV infusion on days 1 and 15 of each 28-day course Erlotinib 150 mg orally daily Imatinib 300 mg orally daily or 400 mg orally daily In the phase II portion: Bevacizumab 10 mg/kg 30-60 minute IV infusion on days 1 and 15 of every 28 day cycle Erlotinib 150 mg orally daily Imatinib 400 mg orally daily | 94 |
| Total | 94 |
Baseline characteristics
| Characteristic | Bevacizumab/Erlotinib/Imatinib |
|---|---|
| Age Continuous | 60 years |
| Region of Enrollment United States | 94 participants |
| Sex: Female, Male Female | 20 Participants |
| Sex: Female, Male Male | 74 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 83 / 94 |
| serious Total, serious adverse events | 45 / 94 |
Outcome results
Primary
Objective Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time frame: 18 months
Population: Eighty-seven of 94 patients (93%) received ≥ 2 months of treatment and were fully evaluable for response. Seven patients discontinued treatment during the first 8 weeks. One of these 7 patients had evidence of rapid tumor progression, whereas the remaining 6 patients discontinued treatment because of toxicity or for personal reasons.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab/Erlotinib/Imatinib | Objective Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment | 17 percentage of participants |
Primary
Overall Survival (OS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death
Time frame: 24 months
Population: All patients enrolled in the study
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab/Erlotinib/Imatinib | Overall Survival (OS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death | 17.2 months |
Primary
Progression Free Survival (PFS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Worsening of Their Disease
Time frame: 18 months
Population: All patients enrolled in the trial
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab/Erlotinib/Imatinib | Progression Free Survival (PFS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Worsening of Their Disease | 8.9 months |