Colorectal Cancer, Metastatic Cancer
Conditions
Keywords
EGFr, Clinical Trial, Panitumumab, ABX-EGF, Immunex, Metastatic Cancer, Vectibix, Abgenix, Amgen
Brief summary
The purpose of this study is to determine that panitumumab will have clinically meaningful anti-tumor activity in patients with metastatic colorectal cancer who have developed progressive disease or relapsed while on or after prior fluoropyrimidine, irinotecan and oxaliplatin chemotherapy.
Detailed description
Panitumumab was administered once every 2 weeks until participants developed progressive disease, were unable to tolerate panitumumab, or discontinued treatment for other reasons (eg, administrative decision). Participants then attended a safety follow-up visit 4 weeks from the last panitumumab infusion. Participants were subsequently contacted every 3 months from the last panitumumab infusion through month 24 to assess disease status and survival.
Interventions
BIOLOGICALPanitumumab
Panitumumab 6 mg/kg every once 2 weeks weeks administered by intravenous (IV) infusion.
Sponsors
Amgen
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
* Pathologic diagnosis of colorectal adenocarcinoma (diagnostic tissue obtained by tissue biopsy) * Metastatic colorectal carcinoma * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 * Documented evidence of disease progression during, or following treatment, with fluoropyrimidine, irinotecan and oxaliplatin chemotherapy for metastatic colorectal cancer * Radiographic documentation of disease progression during or within 6 months following the most recent chemotherapy regimen is required * Bidimensionally measurable disease * Tumor expressing epidermal growth factor receptor (EGFr) by immunohistochemistry * At least 2 but no more than 3 prior chemotherapy regimens for metastatic colorectal cancer * Adequate hematologic, renal and hepatic function
Exclusion criteria
* Symptomatic brain metastases requiring treatment * Patient with a history of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis * Use of systemic chemotherapy or radiotherapy within 30 days before enrollment * Prior epidermal growth factor receptor targeting agents * Prior anti-tumor therapies including prior experimental agents or approved anti-tumor small molecules and biologics of short (less than 1 week) serum half-life within 30 days before enrollment, or prior experimental or approved proteins with longer serum half-life (e.g., AvastinTM) within 6 weeks before enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Objective Tumor Response Through Week 16 | 16 weeks | Confirmed objective tumor response (complete or partial response) based on modified World Health Organization (WHO) criteria, through week 16. Tumor response was assessed by a central Independent Review Committee (IRC) and confirmation 4 weeks after initial assessment was required. Complete Response (CR): Disappearance of all index and non-index lesions and no new lesions. Partial Response (PR): At least a 50% decrease in the sum of the product of the longest diameters (SPD) of index lesions taking as reference the Baseline SPD, and no new non-index lesions and no unequivocal progression of non-index lesions, or, the disappearance of all index lesions and persistence of one or more non-index lesions not qualifying for either CR or Progressive Disease. |
| Duration of Response | Until the data cut-off date of 22 December 2006. Maximum time of follow-up was 128 weeks. | The time from first objective response to first observed progression of disease or death if the death was due to disease progression (whichever comes first); participants who respond and have not progressed while on study or died for reasons other than disease progression while on study were censored at their last evaluable disease assessment date. Response (complete or partial response) was assessed per modified WHO criteria by the central IRC. Complete Response (CR): Disappearance of all index and non-index lesions and no new lesions. Partial Response (PR): At least a 50% decrease in the sum of the product of the longest diameters (SPD) of index lesions taking as reference the Baseline SPD, and no new non-index lesions and no unequivocal progression of non-index lesions, or, the disappearance of all index lesions and persistence of one or more non-index lesions not qualifying for either CR or Progressive Disease. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival Time | Until the data cut-off date of 22 December 2006. Maximum follow-up time was 128 weeks. | Kaplan-Meier estimate of median time from enrollment to death or first observed disease progression (whichever comes first). Participants who did not progress while on study and did not die while on study were censored at the last evaluable disease assessment date. |
| Time to Disease Progression | Until the data cut-off date of 22 December 2006. Maximum follow-up time was 128 weeks. | Kaplan-Meier estimate of the median time from enrollment to first observed disease progression or death if death was due to disease progression (whichever comes first). Participants who did not progress while on study or died for reasons other than disease progression while on study were censored at their last evaluable disease assessment date. |
| Number of Participants With Objective Tumor Response Throughout Study | Until the data cut-off date of 22 December 2006. Maximum time of follow-up was 128 weeks. | Confirmed objective tumor response (complete or partial response) based on modified World Health Organization (WHO) criteria, throughout the duration of the study Tumor response was assessed by a central Independent Review Committee (IRC) and confirmation 4 weeks after initial assessment was required. Complete Response (CR): Disappearance of all index and non-index lesions and no new lesions. Partial Response (PR): At least a 50% decrease in the sum of the product of the longest diameters (SPD) of index lesions taking as reference the Baseline SPD, and no new non-index lesions and no unequivocal progression of non-index lesions, or, the disappearance of all index lesions and persistence of one or more non-index lesions not qualifying for either CR or Progressive Disease. |
| Duration of Stable Disease | Until the data cut-off date of 22 December 2006. Maximum follow-up time was 128 weeks. | Kaplan-Meier estimates of the median time from enrollment to the date of first observed disease progression or death due to disease progression among those participants with a best outcome of stable disease. Stable disease (SD): Neither sufficient shrinkage of Index lesions to qualify for partial response nor sufficient increase to qualify for progressive disease (PD) taking as reference the nadir sum of the products of the longest diameters (SPD) since the treatment started and the disappearance of or persistence of one or more non-index lesions not qualifying for PD. |
| Overall Survival | Until the data cut-off date of 22 December 2006. Maximum follow-up time was 128 weeks. | Kaplan-Meier estimate of median time from enrollment to death from any cause. Deaths were recorded during treatment, safety follow-up and long term follow-up. |
| Time to Treatment Failure | Until the data cut-off date of 22 December 2006. Maximum follow-up time was 128 weeks. | Kaplan-Meier estimate of median time from enrollment to treatment failure, defined as the date the decision was made to end treatment. Participants remaining in the treatment phase at the time of the analysis were censored on their last visit date. |
| Time to Response | Until the data cut-off date of 22 December 2006. Maximum time of follow-up was 128 weeks. | Median time from enrollment to objective tumor response for participants who responded. |
Participant flow
Recruitment details
Participants were enrolled from 1 March 2004 through 19 Jul 2006. Patient disposition is reported up until the data cut-off date of 22 December 2006. Completed study is defined as participants who either died on study or completed the safety follow-up visit (30 days after the last dose of panitumumab).
Participants by arm
| Arm | Count |
|---|---|
| Panitumumab Open-label panitumumab administered by intravenous (IV) infusion at a dose of 6 mg/kg given once every 2 weeks until participants developed progressive disease, were unable to tolerate panitumumab, or discontinued treatment for other reasons. | 185 |
| Total | 185 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Disease Progression | 16 |
| Overall Study | Ineligibility determined | 2 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Non-compliance | 1 |
| Overall Study | Other | 6 |
| Overall Study | Physician Decision | 2 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Panitumumab |
|---|---|
| Age, Continuous | 59.6 Years STANDARD_DEVIATION 10.6 |
| Race/Ethnicity, Customized Aborigine | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants |
| Race/Ethnicity, Customized Asian | 4 Participants |
| Race/Ethnicity, Customized Black or African American | 15 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 19 Participants |
| Race/Ethnicity, Customized Japanese | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race/Ethnicity, Customized Other | 2 Participants |
| Race/Ethnicity, Customized White or Caucasian | 144 Participants |
| Sex: Female, Male Female | 85 Participants |
| Sex: Female, Male Male | 100 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 176 / 182 |
| serious Total, serious adverse events | 62 / 182 |
Outcome results
Primary
Duration of Response
The time from first objective response to first observed progression of disease or death if the death was due to disease progression (whichever comes first); participants who respond and have not progressed while on study or died for reasons other than disease progression while on study were censored at their last evaluable disease assessment date. Response (complete or partial response) was assessed per modified WHO criteria by the central IRC. Complete Response (CR): Disappearance of all index and non-index lesions and no new lesions. Partial Response (PR): At least a 50% decrease in the sum of the product of the longest diameters (SPD) of index lesions taking as reference the Baseline SPD, and no new non-index lesions and no unequivocal progression of non-index lesions, or, the disappearance of all index lesions and persistence of one or more non-index lesions not qualifying for either CR or Progressive Disease.
Time frame: Until the data cut-off date of 22 December 2006. Maximum time of follow-up was 128 weeks.
Population: Subset of the Adjudicated Prior Failures Set, composed of participants confirmed to be eligible by the Independent Eligibility Review Committee (IERC), who had a confirmed obective tumor response
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panitumumab | Duration of Response | 14.0 Weeks |
Primary
Number of Participants With Objective Tumor Response Through Week 16
Confirmed objective tumor response (complete or partial response) based on modified World Health Organization (WHO) criteria, through week 16. Tumor response was assessed by a central Independent Review Committee (IRC) and confirmation 4 weeks after initial assessment was required. Complete Response (CR): Disappearance of all index and non-index lesions and no new lesions. Partial Response (PR): At least a 50% decrease in the sum of the product of the longest diameters (SPD) of index lesions taking as reference the Baseline SPD, and no new non-index lesions and no unequivocal progression of non-index lesions, or, the disappearance of all index lesions and persistence of one or more non-index lesions not qualifying for either CR or Progressive Disease.
Time frame: 16 weeks
Population: Adjudicated Prior Failures Set, composed of participants confirmed to be eligible by the Independent Eligibility Review Committee (IERC)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Panitumumab | Number of Participants With Objective Tumor Response Through Week 16 | 5 Participants |
Secondary
Duration of Stable Disease
Kaplan-Meier estimates of the median time from enrollment to the date of first observed disease progression or death due to disease progression among those participants with a best outcome of stable disease. Stable disease (SD): Neither sufficient shrinkage of Index lesions to qualify for partial response nor sufficient increase to qualify for progressive disease (PD) taking as reference the nadir sum of the products of the longest diameters (SPD) since the treatment started and the disappearance of or persistence of one or more non-index lesions not qualifying for PD.
Time frame: Until the data cut-off date of 22 December 2006. Maximum follow-up time was 128 weeks.
Population: Subset of Adjudicated Prior Failures Set, composed of participants confirmed to be eligible by the Independent Eligibility Review Committee (IERC), with a best outcome of stable disease
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panitumumab | Duration of Stable Disease | 23.9 Weeks |
Secondary
Number of Participants With Objective Tumor Response Throughout Study
Confirmed objective tumor response (complete or partial response) based on modified World Health Organization (WHO) criteria, throughout the duration of the study Tumor response was assessed by a central Independent Review Committee (IRC) and confirmation 4 weeks after initial assessment was required. Complete Response (CR): Disappearance of all index and non-index lesions and no new lesions. Partial Response (PR): At least a 50% decrease in the sum of the product of the longest diameters (SPD) of index lesions taking as reference the Baseline SPD, and no new non-index lesions and no unequivocal progression of non-index lesions, or, the disappearance of all index lesions and persistence of one or more non-index lesions not qualifying for either CR or Progressive Disease.
Time frame: Until the data cut-off date of 22 December 2006. Maximum time of follow-up was 128 weeks.
Population: Adjudicated Prior Failures Set, composed of participants confirmed to be eligible by the Independent Eligibility Review Committee (IERC)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Panitumumab | Number of Participants With Objective Tumor Response Throughout Study | 5 Participants |
Secondary
Overall Survival
Kaplan-Meier estimate of median time from enrollment to death from any cause. Deaths were recorded during treatment, safety follow-up and long term follow-up.
Time frame: Until the data cut-off date of 22 December 2006. Maximum follow-up time was 128 weeks.
Population: Adjudicated Prior Failures Set, composed of participants confirmed to be eligible by the Independent Eligibility Review Committee (IERC)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panitumumab | Overall Survival | 7.0 months |
Secondary
Progression-free Survival Time
Kaplan-Meier estimate of median time from enrollment to death or first observed disease progression (whichever comes first). Participants who did not progress while on study and did not die while on study were censored at the last evaluable disease assessment date.
Time frame: Until the data cut-off date of 22 December 2006. Maximum follow-up time was 128 weeks.
Population: Adjudicated Prior Failures Set, composed of participants confirmed to be eligible by the Independent Eligibility Review Committee (IERC)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panitumumab | Progression-free Survival Time | 7.3 Weeks |
Secondary
Time to Disease Progression
Kaplan-Meier estimate of the median time from enrollment to first observed disease progression or death if death was due to disease progression (whichever comes first). Participants who did not progress while on study or died for reasons other than disease progression while on study were censored at their last evaluable disease assessment date.
Time frame: Until the data cut-off date of 22 December 2006. Maximum follow-up time was 128 weeks.
Population: Adjudicated Prior Failures Set, composed of participants confirmed to be eligible by the Independent Eligibility Review Committee (IERC)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panitumumab | Time to Disease Progression | 7.3 Weeks |
Secondary
Time to Response
Median time from enrollment to objective tumor response for participants who responded.
Time frame: Until the data cut-off date of 22 December 2006. Maximum time of follow-up was 128 weeks.
Population: Subset of Adjudicated Prior Failures Set, composed of participants confirmed to be eligible by the Independent Eligibility Review Committee (IERC), who had a confirmed objective tumor response
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panitumumab | Time to Response | 11.0 Weeks |
Secondary
Time to Treatment Failure
Kaplan-Meier estimate of median time from enrollment to treatment failure, defined as the date the decision was made to end treatment. Participants remaining in the treatment phase at the time of the analysis were censored on their last visit date.
Time frame: Until the data cut-off date of 22 December 2006. Maximum follow-up time was 128 weeks.
Population: Adjudicated Prior Failures Set, composed of participants confirmed to be eligible by the Independent Eligibility Review Committee (IERC)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panitumumab | Time to Treatment Failure | 8.0 Weeks |