Renal Cell Cancer
Conditions
Brief summary
This single arm study will assess the efficacy and safety of Avastin in combination with interferon alfa-2a and vinblastine as first line treatment in patients with metastatic renal cell cancer. Patients will receive Avastin (15mg/kg iv) every 3 weeks, interferon alfa-2a 3 times weekly (3 Mio IU sc escalating to 18 Mio sc) and vinblastine (0.1mg/kg iv) every 3 weeks. The anticipated time on study treatment is until tumor progression, and the target sample size is 100-500 individuals.
Interventions
DRUGbevacizumab [Avastin]
15mg/kg iv every 3 weeks
3 MioIU sc escalating to 18 MioIU sc, 3 times weekly
DRUGVinblastine
0.1mg/kg iv every 3 weeks
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* adult patients, \>=18 years of age; * metastatic renal cell cancer of predominantly clear cell type; * \>=1 measurable lesion.
Exclusion criteria
* prior treatment with chemotherapy, cytokine or tyrosine kinase inhibitor therapy for metastatic renal cell cancer; * ongoing or recent need for full therapeutic dose of anticoagulants or chronic daily treatment with aspirin (\>325mg/day); * clinically significant cardiovascular disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Disease Progression or Death | Days 0, 91, 182, 273, 365, 456, and 547 | Disease progression was evaluated according to the Response Evaluation Criteria In Solid Tumors (RECIST) using computed tomography (CT) scans (preferred method), magnetic resonance imaging (MRI) scans, X-ray, bone scans, or clinical examination. |
| PFS - Time to Event | Days 0, 91, 182, 273, 365, 456, and 547 | PFS was defined as the time in days from the date of treatment start to the date of first documented disease progression or death. Disease progression was evaluated according to RECIST using CT scans (preferred method), MRI scans, X-ray, bone scans, or clinical examination. Median PFS was estimated using the Kaplan-Meier method |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Objective Response (OR) | Baseline and Cycles 3, 6, 9, 13, and 17 | Percentage of participants with OR based on assessment of confirmed complete remission (CR) or confirmed partial remission (PR) according to RECIST. |
| Overall Survival (OS) | Baseline, Day 1 of every cycle to disease progression or death (up to Week 102) | OS was defined as the duration from treatment start to death from any cause. Overall survival was censored at the last contact for surviving participants and missing data points. |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bevacizumab + IFN/Vinblastine Cycle 1 (3-week cycle): Participants received vinblastine sulfate 0.1 mg/kg IV and bevacizumab 15 mg/kg IV on Day 1 followed by 2 weeks off and IFN SC injection three times per week (starting on Day 1) at doses of 3 mIU (Week 1), 9 mIU (Week 2), and 18 mIU (Week 3).
Cycles 2 to 17 (3-week cycles): Participants received vinblastine sulfate 0.1 mg/kg IV and bevacizumab 15 mg/kg IV on Day 1 followed by 2 weeks off and IFN 18 mIU SC injection three times per week during Weeks 1 through 3 (starting on Day 1); the cycle was repeated every 3 weeks up to Week 51 (Cycle 17) or to tumor progression.
If the first 17 cycles were tolerated without tumor progression, participants received bevacizumab monotherapy: bevacizumab 15 mg/kg IV on Day 1 followed by 2 weeks off; this cycle was repeated every 3 weeks up to Week 102 (Cycle 34) or to tumor progression. | 25 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Bevacizumab + IFN/Vinblastine | Adverse Event | 4 |
| Bevacizumab + IFN/Vinblastine | Death | 2 |
| Bevacizumab + IFN/Vinblastine | Discontinuation of study/background drug | 1 |
| Bevacizumab + IFN/Vinblastine | Protocol Deviation affecting safety | 1 |
| Bevacizumab + IFN/Vinblastine | Radiological progression of cancer | 6 |
| Bevacizumab + IFN/Vinblastine | Withdrawal of consent | 4 |
| Bevacizumab Monotherapy | Radiological progression of cancer | 1 |
| Bevacizumab Monotherapy | Symptomatic progression of cancer | 1 |
Baseline characteristics
| Characteristic | Bevacizumab + IFN/Vinblastine |
|---|---|
| Age, Continuous | 62.2 years STANDARD_DEVIATION 8.5 |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 22 / 25 |
| serious Total, serious adverse events | 8 / 25 |
Outcome results
Primary
Percentage of Participants With Disease Progression or Death
Disease progression was evaluated according to the Response Evaluation Criteria In Solid Tumors (RECIST) using computed tomography (CT) scans (preferred method), magnetic resonance imaging (MRI) scans, X-ray, bone scans, or clinical examination.
Time frame: Days 0, 91, 182, 273, 365, 456, and 547
Population: Intent-to-treat (ITT) population: all participants, even those who withdrew from the study prematurely, who received at least 1 dose of study medication and for whom the primary efficacy variable was measured at least once during the time when the participant received study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab + IFN/Vinblastine | Percentage of Participants With Disease Progression or Death | 66.9 percentage of participants |
Primary
PFS - Time to Event
PFS was defined as the time in days from the date of treatment start to the date of first documented disease progression or death. Disease progression was evaluated according to RECIST using CT scans (preferred method), MRI scans, X-ray, bone scans, or clinical examination. Median PFS was estimated using the Kaplan-Meier method
Time frame: Days 0, 91, 182, 273, 365, 456, and 547
Population: ITT population.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Bevacizumab + IFN/Vinblastine | PFS - Time to Event | 274 days | Standard Error 31.6 |
Secondary
Overall Survival (OS)
OS was defined as the duration from treatment start to death from any cause. Overall survival was censored at the last contact for surviving participants and missing data points.
Time frame: Baseline, Day 1 of every cycle to disease progression or death (up to Week 102)
Population: Two of 25 participants died during the course of the study, thus, median overall survival could not be analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab + IFN/Vinblastine | Overall Survival (OS) | NA weeks |
Secondary
Percentage of Participants With Objective Response (OR)
Percentage of participants with OR based on assessment of confirmed complete remission (CR) or confirmed partial remission (PR) according to RECIST.
Time frame: Baseline and Cycles 3, 6, 9, 13, and 17
Population: ITT Population; missing data were imputed using the last observation carried forward (LOCF) technique. Number (n) equals (=) number of participants assessed at each specific visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bevacizumab + IFN/Vinblastine | Percentage of Participants With Objective Response (OR) | Week 18 (n=16) | 31.3 percentage of participants |
| Bevacizumab + IFN/Vinblastine | Percentage of Participants With Objective Response (OR) | Week 27 (n=16) | 37.5 percentage of participants |
| Bevacizumab + IFN/Vinblastine | Percentage of Participants With Objective Response (OR) | Week 39 (n=16) | 31.3 percentage of participants |
| Bevacizumab + IFN/Vinblastine | Percentage of Participants With Objective Response (OR) | Week 51 (n=16) | 31.3 percentage of participants |
| Bevacizumab + IFN/Vinblastine | Percentage of Participants With Objective Response (OR) | Week 9 (n=14) | 21.4 percentage of participants |