Solid Tumor
Conditions
Keywords
Phase Ib Phase II Advanced solid tumor Clear cell renal cancer Sunitinib plus / minus CVX-060
Brief summary
The safety and tolerability of CVX-060 have been established in the first-in-human clinical trial, CVX-060-101. Thus, this phase Ib/II trial is to assess the safety and pharmacokinetics (PK) profiles of combining CVX-060 with sunitinib in patients with advanced solid tumors, and to subsequently assess the treatment efficacy of the combination treatment, as well as that of sunitinib alone in patients with advanced renal cell carcinoma (mRCC).
Detailed description
On 23-Nov-2010, B1131001 (CVX-060-102) was closed to enrollment due to emerging clinical data which led to a re-assessment of the strategic goals of the PF-04856884 program. The study enrolled the Phase 1b portion only. Subsequently, on 25-Oct-2012, due to data safety signals in a separate clinical trial with PF-04856884 (CVX-060), all PF-04856884 studies were discontinued and ongoing patients on B1131001 were permitted to remain on study at a reduced PF-04856884 dose if determined to have been deriving clinical benefit.
Interventions
DRUGCVX-060 + sunitinib
CVX-060 weekly infusions at 6.0 mg/kg + 50 mg sunitinib daily (4 out of 6 weeks)
DRUGSunitinib
50 mg sunitinib daily (4 out of 6 weeks)
Sponsors
Pfizer
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
* Histologically or cytologically confirmed advanced/metastatic solid tumor * Having received at least 1 prior systemic therapy for the treatment of advanced/metastatic solid tumors * Histologically or cytologically confirmed renal cell carcinoma with clear cell histology and evidence of metastasis (No previous systemic therapy for the treatment of metastatic renal cell carcinoma) * Adequate laboratory tests * Eastern Cooperative Oncology Group (ECOG) 0-1, Life expectancy \> or = 12 weeks and age \> or = 18 years
Exclusion criteria
* Patients intolerant of prior anti-angiogenic agents * Recent history of bleeding or bleeding disorders * History of tumors in the brain * History of heart problems * History of severe allergic reaction to antibody therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) | Baseline up to Cycle 1( Day 1 to Day 42) | The MTD was defined as the dose level at which less than or equal to (\<=) 1/6 participants experienced Dose Limiting Toxicity (DLT) during the first cycle of treatment with the next higher dose having \>= 2/6 participants with DLT. |
| Progression-free Survival (PFS) | Baseline tumor progression/clinical deterioration or death (up to 28 days post last dose of study medication) | PFS was defined as the time from the first dose date to the first documentation of disease progression or death due to any cause, whichever occurred first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Angiopoietin-2 (Ang-2) and Plasma Vascular Endothelial Growth Factor (VEGF) Levels | Ang-2 (Day 1, 2, 5, 8, 22, 29 Cycle 1, Day 1 Cycle 2 up to Cycle 28); VEGF (Day 1, 8, 15, 22 Cycle 1, Day 1 Cycle 2 up to Cycle 28) | — |
| Number of Participants With Treatment Emergent Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs) | Baseline up to 28 days post last dose of study medication | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pre treatment state. |
| Pharmacokinetic Parameters of CVX-060 | Pre-dose on Day 1 Cycle 1 ; post-dose on Day 1, 5, 8, 15, 22, 29 Cycle 1 , Day 1 Cycle 2, to Cycle 28 , end of study (7 days post last dose of study medication), follow-up visit (28 days post last dose of study medication) | Pharmacokinetic parameters Area under the Curve (AUC), Maximum Observed Serum Concentration (Cmax), Minimum Observed Serum Trough Concentration (Cmin), Clearance (CL), terminal elimination half life (t1/2) were planned to be analyzed. |
| Duration of Response | Baseline up to 7 days post last dose of study medication | Duration of response is defined as the time from the first documentation of objective tumor response to the first documentation of objective tumor progression or death due to any cause, whichever occurs first. Participants last known to be progression free are censored at the date of the last objective disease assessment that verified lack of disease progression. |
| Number of Participants With Anti- CVX-060 Antibodies | Baseline up to 28 days after last CVX-060 dose | — |
| Percentage of Participants With Objective Response | Baseline up to 7 days post last dose of study medication | Percentage of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. Per RECIST v1.0: CR defined as disappearance of all target lesions and non-target lesions. PR defined as \>= 30% decrease in sum of the longest diameters (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST associated to non-progressive disease response for non target lesions. |
| Number of Participants With Dose-limiting Toxicities (DLT) | Baseline up to 28 days post last dose of study medication | DLT included grade 4 neutropenia of \>= 3 day duration or with grade 4 neutropenia associated with fever; grade 4 thrombocytopenia for \>= 3 consecutive days; Proteinuria of \>=2 grams (g) per 24 hours; inability to resume to CVX-060 or sunitinib within 14 days of scheduled administration due to treatment related toxicity; any Grade 3 nonhematologic toxicity except nausea, vomiting, and diarrhea; Grade 3 nausea, vomiting, or diarrhea which persists for \>=48 hours; Any \>= Grade 4 non-hematologic toxicity; Any additional hematological or non-hematological toxicity for which dose reduction was required or for which patient was discontinued from the trial. |
Countries
United States
Participant flow
Pre-assignment details
The study was planned to be conducted in 2 phases, Phase 1b and Phase 2. On 23 Nov 2010, this study was closed to enrollment due to emerging clinical data which led to a re-assessment of strategic goals of the CVX-060 program. The study enrolled the Phase 1b portion only.
Participants by arm
| Arm | Count |
|---|---|
| CVX-060 6 mg/kg + Sunitinib 50 mg CVX-060 6 milligram per kilogram (mg/kg) of body weight intravenous infusion administered once-weekly with oral 50 mg sunitinib capsule once daily up to 4 weeks followed by 2 weeks of off treatment (6-week cycle) until disease progression, unacceptable toxicity, withdrawal of consent or investigator's discretion. | 12 |
| CVX-060 6 mg/kg + Sunitinib 37.5 mg CVX-060 6 mg/kg of body weight intravenous infusion administered once-weekly with oral 37.5 mg sunitinib capsule once daily up to 4 weeks followed by 2 weeks off (6-week cycle) treatment until disease progression, unacceptable toxicity, withdrawal of consent or investigator's discretion. | 3 |
| CVX-060 12 mg/kg + Sunitinib 50 mg CVX-060 12 mg/kg of body weight intravenous infusion administered once-weekly with oral 50 mg sunitinib capsule once daily up to 4 weeks followed by 2 weeks off treatment (6-week cycle) until disease progression, unacceptable toxicity, withdrawal of consent or investigator's discretion. | 3 |
| CVX-060 15 mg/kg + Sunitinib 50 mg CVX-060 15 mg/kg of body weight intravenous infusion administered once-weekly with oral 50 mg sunitinib capsule once daily up to 4 weeks followed by 2 weeks off treatment (6-week cycle) until disease progression, unacceptable toxicity, withdrawal of consent or investigator's discretion. | 16 |
| Total | 34 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Death | 1 | 0 | 1 | 1 |
| Overall Study | On going at date of cut-off | 0 | 0 | 0 | 1 |
| Overall Study | Other | 0 | 0 | 0 | 4 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 3 |
Baseline characteristics
| Characteristic | CVX-060 6 mg/kg + Sunitinib 50 mg | Total | CVX-060 15 mg/kg + Sunitinib 50 mg | CVX-060 12 mg/kg + Sunitinib 50 mg | CVX-060 6 mg/kg + Sunitinib 37.5 mg |
|---|---|---|---|---|---|
| Age, Customized 18 to 44 years | 0 Participants | 2 Participants | 2 Participants | 0 Participants | 0 Participants |
| Age, Customized 45 to 64 years | 6 Participants | 20 Participants | 9 Participants | 3 Participants | 2 Participants |
| Age, Customized Greater than or equal to (>=) 65 years | 6 Participants | 12 Participants | 5 Participants | 0 Participants | 1 Participants |
| Age, Customized Less than (<) 18 years | 0 Participants 9.6 | 0 Participants | 0 Participants 13.7 | 0 Participants 8.5 | 0 Participants 8.5 |
| Sex: Female, Male Female | 6 Participants | 14 Participants | 4 Participants | 2 Participants | 2 Participants |
| Sex: Female, Male Male | 6 Participants | 20 Participants | 12 Participants | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 12 / 12 | 3 / 3 | 3 / 3 | 16 / 16 |
| serious Total, serious adverse events | 4 / 12 | 0 / 3 | 1 / 3 | 8 / 16 |
Outcome results
Primary
Maximum Tolerated Dose (MTD)
The MTD was defined as the dose level at which less than or equal to (\<=) 1/6 participants experienced Dose Limiting Toxicity (DLT) during the first cycle of treatment with the next higher dose having \>= 2/6 participants with DLT.
Time frame: Baseline up to Cycle 1( Day 1 to Day 42)
Population: The study was terminated during the Phase 1b phase by the sponsor prematurely. Due to the decision of not conducting the Phase II portion of the study, no MTD was assessed.
Primary
Progression-free Survival (PFS)
PFS was defined as the time from the first dose date to the first documentation of disease progression or death due to any cause, whichever occurred first.
Time frame: Baseline tumor progression/clinical deterioration or death (up to 28 days post last dose of study medication)
Population: The study was terminated during the Phase 1b phase by the sponsor prematurely. Due to the decision of not conducting the Phase II portion of the study.The PFS endpoint was a pre-specified endpoint for the Phase II portion of the study, and was therefore not assessed.
Secondary
Duration of Response
Duration of response is defined as the time from the first documentation of objective tumor response to the first documentation of objective tumor progression or death due to any cause, whichever occurs first. Participants last known to be progression free are censored at the date of the last objective disease assessment that verified lack of disease progression.
Time frame: Baseline up to 7 days post last dose of study medication
Population: Duration of response was not calculated as there were no participants with objective response.
Secondary
Number of Participants With Anti- CVX-060 Antibodies
Time frame: Baseline up to 28 days after last CVX-060 dose
Population: The study was terminated during the Phase 1b phase by the sponsor prematurely. Due to the decision of not conducting the phase II portion of the study, no Anti-CVX-060 antibody assessment was conducted.
Secondary
Number of Participants With Dose-limiting Toxicities (DLT)
DLT included grade 4 neutropenia of \>= 3 day duration or with grade 4 neutropenia associated with fever; grade 4 thrombocytopenia for \>= 3 consecutive days; Proteinuria of \>=2 grams (g) per 24 hours; inability to resume to CVX-060 or sunitinib within 14 days of scheduled administration due to treatment related toxicity; any Grade 3 nonhematologic toxicity except nausea, vomiting, and diarrhea; Grade 3 nausea, vomiting, or diarrhea which persists for \>=48 hours; Any \>= Grade 4 non-hematologic toxicity; Any additional hematological or non-hematological toxicity for which dose reduction was required or for which patient was discontinued from the trial.
Time frame: Baseline up to 28 days post last dose of study medication
Population: Safety Analysis set consisted of all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | Number of Participants With Dose-limiting Toxicities (DLT) | 2 participants |
| CVX-060 6 mg/kg + Sunitinib 37.5 mg | Number of Participants With Dose-limiting Toxicities (DLT) | 1 participants |
| CVX-060 12 mg/kg + Sunitinib 50 mg | Number of Participants With Dose-limiting Toxicities (DLT) | 0 participants |
| CVX-060 15 mg/kg + Sunitinib 50 mg | Number of Participants With Dose-limiting Toxicities (DLT) | 2 participants |
Secondary
Number of Participants With Treatment Emergent Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs)
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pre treatment state.
Time frame: Baseline up to 28 days post last dose of study medication
Population: Safety Analysis set consisted of all participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Participants | Number of Participants With Treatment Emergent Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs) | SAEs | 4 Participants |
| All Participants | Number of Participants With Treatment Emergent Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs) | non-SAEs | 12 Participants |
| CVX-060 6 mg/kg + Sunitinib 37.5 mg | Number of Participants With Treatment Emergent Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs) | non-SAEs | 3 Participants |
| CVX-060 6 mg/kg + Sunitinib 37.5 mg | Number of Participants With Treatment Emergent Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs) | SAEs | 0 Participants |
| CVX-060 12 mg/kg + Sunitinib 50 mg | Number of Participants With Treatment Emergent Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs) | non-SAEs | 3 Participants |
| CVX-060 12 mg/kg + Sunitinib 50 mg | Number of Participants With Treatment Emergent Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs) | SAEs | 1 Participants |
| CVX-060 15 mg/kg + Sunitinib 50 mg | Number of Participants With Treatment Emergent Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs) | SAEs | 8 Participants |
| CVX-060 15 mg/kg + Sunitinib 50 mg | Number of Participants With Treatment Emergent Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs) | non-SAEs | 16 Participants |
Secondary
Percentage of Participants With Objective Response
Percentage of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. Per RECIST v1.0: CR defined as disappearance of all target lesions and non-target lesions. PR defined as \>= 30% decrease in sum of the longest diameters (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST associated to non-progressive disease response for non target lesions.
Time frame: Baseline up to 7 days post last dose of study medication
Population: Safety Analysis set consisted of all participants who received at least 1 dose of study medication. Here 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | Percentage of Participants With Objective Response | 0 Percentage of participants |
| CVX-060 6 mg/kg + Sunitinib 37.5 mg | Percentage of Participants With Objective Response | 0 Percentage of participants |
| CVX-060 12 mg/kg + Sunitinib 50 mg | Percentage of Participants With Objective Response | 0 Percentage of participants |
| CVX-060 15 mg/kg + Sunitinib 50 mg | Percentage of Participants With Objective Response | 0 Percentage of participants |
Secondary
Pharmacokinetic Parameters of CVX-060
Pharmacokinetic parameters Area under the Curve (AUC), Maximum Observed Serum Concentration (Cmax), Minimum Observed Serum Trough Concentration (Cmin), Clearance (CL), terminal elimination half life (t1/2) were planned to be analyzed.
Time frame: Pre-dose on Day 1 Cycle 1 ; post-dose on Day 1, 5, 8, 15, 22, 29 Cycle 1 , Day 1 Cycle 2, to Cycle 28 , end of study (7 days post last dose of study medication), follow-up visit (28 days post last dose of study medication)
Population: The study was terminated during the Phase 1b phase by the sponsor prematurely. Due to the decision of not conducting the phase II portion of the study,pharmacokinetics assessment was not conducted.
Secondary
Serum Angiopoietin-2 (Ang-2) and Plasma Vascular Endothelial Growth Factor (VEGF) Levels
Time frame: Ang-2 (Day 1, 2, 5, 8, 22, 29 Cycle 1, Day 1 Cycle 2 up to Cycle 28); VEGF (Day 1, 8, 15, 22 Cycle 1, Day 1 Cycle 2 up to Cycle 28)
Population: The study was terminated during the Phase 1b phase by the sponsor prematurely. Due to the decision of not conducting the phase II portion of the study, pharmacodynamics assessment was not conducted.