Colorectal Cancer, Metastases
Conditions
Keywords
Colon, Rectal Cancer, ABX-EGF, Panitumumab, EGFr, Immunex, Abgenix, Amgen, Metastatic Colorectal Cancer, Vectibix
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.
Interventions
DRUGPanitumumab
Administered by intravenous 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 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 low to negative levels of 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 anti-EGFr antibody therapy with the exception of the small molecule EGFr tyrosine kinase inhibitors, which are permitted * 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 within 6 weeks before enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Tumor Response Through Week 16 | From enrollment through Week 16 | Confirmed objective tumor response was defined as a complete response or partial response from enrollment through Week 16. Tumor response was monitored, beginning at Week 8, per a modified version of the World Health Organization (WHO) criteria for tumor response and progression by an independent review committee central assessment. Complete response was defined per modified WHO criteria as disappearance of all lesions (index and non-index). Partial response was defined as ≥ 50% decrease from Baseline in the sum of the products of the longest diameters (SPD) of index lesions. Scans were required to confirm a complete or partial response no earlier than 4 weeks from the time a response of complete or partial response was first documented. |
| Duration of Response | From enrollment until the data cut-off date of 22 December 2006. The median follow-up time was 36 weeks. | Kaplan-Meier estimate of time time from first objective response to first observed progression of disease or death if the death was due to disease progression (whichever comes first) among participants who had a response at any time on study. Participants who responded and did not progress while on study or who died for reasons other than disease progression while on study were censored at their last evaluable assessment date. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Tumor Response Throughout the Study | From enrollment until the data cut-off date of 22 December 2006. The median follow-up time was 36 weeks. | Confirmed objective tumor response was defined as a complete response or partial response from enrollment through to the data cut-ff date. Tumor response was monitored, beginning at Week 8, per a modified version of the World Health Organization (WHO) criteria for tumor response and progression by an independent review committee central assessment. Complete response was defined per modified WHO criteria as disappearance of all lesions (index and non-index). Partial response was defined as ≥ 50% decrease from Baseline in the sum of the products of the longest diameters (SPD) of index lesions. Scans were required to confirm a complete or partial response no earlier than 4 weeks from the time a response of complete or partial response was first documented. |
| Time to Initial Objective Response | From enrollment until the data cut-off date of 22 December 2006. The median follow-up time was 36 weeks. | Time from date of enrollment to first objective response; participants with stable disease at their last evaluable assessment date were censored at this date and participants with progressive disease while on study were censored after the last response was observed for all participants. |
| Progression-free Survival Time | From enrollment until the data cut-off date of 22 December 2006. The median follow-up time was 36 weeks. | Kaplan-Meier estimate of median time from date of enrollment to date of first observed progression or death (whichever comes first); participants who did not progress while on study and did not die while on study were censored at their last evaluable assessment date. |
| Time to Disease Progression | From enrollment until the data cut-off date of 22 December 2006. The median follow-up time was 36 weeks. | Kaplan-Meier estimate of median time from date of enrollment to date of first observed progression or death date if the death was due to disease progression (whichever comes first); participants who have not progressed while on study or died for reasons other than disease progression while on study were censored at their last evaluable assessment date. |
| Time to Treatment Failure | From enrollment until the data cut-off date of 22 December 2006. The median follow-up time was 36 weeks. | Kaplan-Meier estimate of median time from date of enrollment to date decision was made to end the treatment phase for any reason; participants who complete the treatment phase or who remain in the treatment phase at the completion of the study were censored at this time. |
| Duration of Stable Disease | From enrollment until the data cut-off date of 22 December 2006. The median follow-up time was 36 weeks. | Kaplan-Meier estimate of median time from date of enrollment to date of first observed progression or death date if the death was due to disease progression (whichever comes first); in those participants who had a best response of stable disease. Stable Disease is defined as neither sufficient shrinkage of index lesions to qualify for a partial response nor sufficient increase to qualify for progressive disease taking as reference the nadir sum of the products of the longest diameters since the treatment started. |
| Overall Survival | From enrollment until the data cut-off date of 22 December 2006. The median follow-up time was 36 weeks. | Kaplan-Meier estimate of time to death from any cause; participants who had not died while on study or were lost to follow-up were censored at their last contact date. |
Participant flow
Recruitment details
Participants were enrolled from 11 August 2004 through 2 August 2006
Participants by arm
| Arm | Count |
|---|---|
| Panitumumab Panitumumab was administered by intravenous (IV) infusion at a dose of 6 mg/kg once every 2 weeks until participants developed progressive disease, were unable to tolerate investigational product, or discontinued for other reasons. | 203 |
| Total | 203 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Death | 17 |
| Overall Study | Disease Progression | 12 |
| Overall Study | Ineligibility determined | 1 |
| Overall Study | Lost to Follow-up | 3 |
| Overall Study | Other | 2 |
| Overall Study | Withdrawal by Subject | 6 |
Baseline characteristics
| Characteristic | Panitumumab |
|---|---|
| Age, Continuous | 62 years |
| Race/Ethnicity, Customized American Indian or Alaska Native | 2 participants |
| Race/Ethnicity, Customized Asian | 3 participants |
| Race/Ethnicity, Customized Black or African American | 34 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 13 participants |
| Race/Ethnicity, Customized White or Caucasian | 151 participants |
| Sex: Female, Male Female | 89 Participants |
| Sex: Female, Male Male | 114 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 200 / 203 |
| serious Total, serious adverse events | 61 / 203 |
Outcome results
Primary
Duration of Response
Kaplan-Meier estimate of time time from first objective response to first observed progression of disease or death if the death was due to disease progression (whichever comes first) among participants who had a response at any time on study. Participants who responded and did not progress while on study or who died for reasons other than disease progression while on study were censored at their last evaluable assessment date.
Time frame: From enrollment until the data cut-off date of 22 December 2006. The median follow-up time was 36 weeks.
Population: Subset of Adjudicated Prior Failures Analysis Set, composed of all consented and enrolled participants who were determined to be eligible by the Independent Eligibility Review Committee (IERC), who had a confirmed objective tumor response at any time on study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panitumumab | Duration of Response | 22.2 weeks |
Primary
Objective Tumor Response Through Week 16
Confirmed objective tumor response was defined as a complete response or partial response from enrollment through Week 16. Tumor response was monitored, beginning at Week 8, per a modified version of the World Health Organization (WHO) criteria for tumor response and progression by an independent review committee central assessment. Complete response was defined per modified WHO criteria as disappearance of all lesions (index and non-index). Partial response was defined as ≥ 50% decrease from Baseline in the sum of the products of the longest diameters (SPD) of index lesions. Scans were required to confirm a complete or partial response no earlier than 4 weeks from the time a response of complete or partial response was first documented.
Time frame: From enrollment through Week 16
Population: Adjudicated Prior Failures Analysis Set, composed of all consented and enrolled participants who were determined to be eligible by the Independent Eligibility Review Committee (IERC).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Panitumumab | Objective Tumor Response Through Week 16 | 6 participants |
Secondary
Duration of Stable Disease
Kaplan-Meier estimate of median time from date of enrollment to date of first observed progression or death date if the death was due to disease progression (whichever comes first); in those participants who had a best response of stable disease. Stable Disease is defined as neither sufficient shrinkage of index lesions to qualify for a partial response nor sufficient increase to qualify for progressive disease taking as reference the nadir sum of the products of the longest diameters since the treatment started.
Time frame: From enrollment until the data cut-off date of 22 December 2006. The median follow-up time was 36 weeks.
Population: Subset of Adjudicated Prior Failures Analysis Set, composed of all consented and enrolled participants who were determined to be eligible by the Independent Eligibility Review Committee (IERC), who had a best response of stable disease.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panitumumab | Duration of Stable Disease | 16.0 weeks |
Secondary
Objective Tumor Response Throughout the Study
Confirmed objective tumor response was defined as a complete response or partial response from enrollment through to the data cut-ff date. Tumor response was monitored, beginning at Week 8, per a modified version of the World Health Organization (WHO) criteria for tumor response and progression by an independent review committee central assessment. Complete response was defined per modified WHO criteria as disappearance of all lesions (index and non-index). Partial response was defined as ≥ 50% decrease from Baseline in the sum of the products of the longest diameters (SPD) of index lesions. Scans were required to confirm a complete or partial response no earlier than 4 weeks from the time a response of complete or partial response was first documented.
Time frame: From enrollment until the data cut-off date of 22 December 2006. The median follow-up time was 36 weeks.
Population: Adjudicated Prior Failures Analysis Set, composed of all consented and enrolled participants who were determined to be eligible by the Independent Eligibility Review Committee (IERC).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Panitumumab | Objective Tumor Response Throughout the Study | 7 participants |
Secondary
Overall Survival
Kaplan-Meier estimate of time to death from any cause; participants who had not died while on study or were lost to follow-up were censored at their last contact date.
Time frame: From enrollment until the data cut-off date of 22 December 2006. The median follow-up time was 36 weeks.
Population: Adjudicated Prior Failures Analysis Set, composed of all consented and enrolled participants who were determined to be eligible by the Independent Eligibility Review Committee (IERC).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panitumumab | Overall Survival | 9.0 months |
Secondary
Progression-free Survival Time
Kaplan-Meier estimate of median time from date of enrollment to date of first observed progression or death (whichever comes first); participants who did not progress while on study and did not die while on study were censored at their last evaluable assessment date.
Time frame: From enrollment until the data cut-off date of 22 December 2006. The median follow-up time was 36 weeks.
Population: Adjudicated Prior Failures Analysis Set, composed of all consented and enrolled participants who were determined to be eligible by the Independent Eligibility Review Committee (IERC).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panitumumab | Progression-free Survival Time | 8.1 weeks |
Secondary
Time to Disease Progression
Kaplan-Meier estimate of median time from date of enrollment to date of first observed progression or death date if the death was due to disease progression (whichever comes first); participants who have not progressed while on study or died for reasons other than disease progression while on study were censored at their last evaluable assessment date.
Time frame: From enrollment until the data cut-off date of 22 December 2006. The median follow-up time was 36 weeks.
Population: Adjudicated Prior Failures Analysis Set, composed of all consented and enrolled participants who were determined to be eligible by the Independent Eligibility Review Committee (IERC).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panitumumab | Time to Disease Progression | 8.3 weeks |
Secondary
Time to Initial Objective Response
Time from date of enrollment to first objective response; participants with stable disease at their last evaluable assessment date were censored at this date and participants with progressive disease while on study were censored after the last response was observed for all participants.
Time frame: From enrollment until the data cut-off date of 22 December 2006. The median follow-up time was 36 weeks.
Population: Subset of Adjudicated Prior Failures Analysis Set, composed of all consented and enrolled participants who were determined to be eligible by the Independent Eligibility Review Committee (IERC), who had an objective tumor response at any time on study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panitumumab | Time to Initial Objective Response | 11 weeks |
Secondary
Time to Treatment Failure
Kaplan-Meier estimate of median time from date of enrollment to date decision was made to end the treatment phase for any reason; participants who complete the treatment phase or who remain in the treatment phase at the completion of the study were censored at this time.
Time frame: From enrollment until the data cut-off date of 22 December 2006. The median follow-up time was 36 weeks.
Population: Subset of Adjudicated Prior Failures Analysis Set, composed of all consented and enrolled participants who were determined to be eligible by the Independent Eligibility Review Committee (IERC), for whom a decision was made to end treatment for any reason.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panitumumab | Time to Treatment Failure | 8.4 weeks |