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Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Panitumumab

Antineoplastic Agents, Immunological

6mg/kg of panitumumab administered once every 2 weeks until subjects develop disease progression or are unable to tolerate the study drug

Panitumumab 9 mg/kg administered once every 3 weeks until subjects develop disease progression or are unable to tolerate the study drug.

panitumumab (ABX-EGF)

The purpose of this study is to evaluate the safety and pharmacokinetics of two dose schedules of panitumumab in subjects with advanced solid tumors.

Two Dose Schedules of Panitumumab in Subjects With Advanced Solid Tumors

An Open-Label, Clinical Trial Evaluating the Safety and Pharmacokinetics of Two Dose Schedules of Panitumumab in Subjects With Advanced Solid Tumors

Amgen

Global Development Leader

Neoplasms

Symptoms and General Pathology

All Conditions

Digestive System Diseases

Neoplasm Metastasis

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Analgesics

Anti-Infective Agents

Herbal and Botanical

Anti-Bacterial Agents

Antibiotics, Antitubercular

Mitogens

Cola

Panitumumab will be administered by intravenous infusion at a dose of 6 mg/kg once every 2 weeks until participants develop progressive disease or are unable to tolerate study drug. Participants will also receive best supportive care (BSC) as judged appropriate by the investigator and according to institutional guidelines.

Best supportive care will be defined in this study as the best care available as judged appropriate by the investigator and according to institutional guidelines and will include antibiotics, analgesics, radiation therapy for pain control (limited to bone metastases), corticosteroids, transfusions, psychotherapy, growth factors, palliative surgery, or any symptomatic therapy as clinically indicated. For the purpose of this study, best supportive care will not include anti-neoplastic chemotherapy.

Best supportive care as site routine excluding: antineoplastic chemotherapy, investigational agents, anti-EGFr(Epidermal growth factor receptor) targeting agents other than ABX-EGF(Panitumumab), experimental or approved anti-tumor therapies (e.g. Avastin), chemotherapy, radiotherapy (with the exception of radiotherapy for pain control limited to bone metastases).

Best supportive care

Intravenous infusion at a dose of 6 mg/kg once every 2 weeks.

The purpose of this study is to determine that panitumumab, using the proposed regimen, will safely increase progression free survival in patients with metastatic colorectal cancer who have failed available treatment options (i.e., patients who developed progressive disease or relapsed while on or after prior fluoropyrimidine, irinotecan and oxaliplatin chemotherapy).

Evaluating Panitumumab (ABX-EGF) Plus Best Supportive Care Versus Best Supportive Care in Patients With Metastatic Colorectal Cancer

An Open-label, Randomized, Phase 3 Clinical Trial of ABX-EGF Plus Best Supportive Care Versus Best Supportive Care in Subjects With Metastatic Colorectal Cancer

Kaplan-Meier estimates of median time from randomization to either death or first observed disease progression, whichever occurred first. Participants were evaluated for tumor response according to modified Response Evaluation Criteria in Solid Tumors (RECIST) based on the response assessment from a blinded review of radiographic scans by the Independent Review Committee. Progressive disease defined as least a 20% increase in the sum of the longest diameters (SLD) of target lesions, taking as reference the nadir SLD recorded since the treatment started or the appearance of one or more new lesions, or the unequivocal progression of existing non-target lesions.

Kaplan-Meier estimates of median time from randomization to death.

Defined as the number of participants with a confirmed complete or partial tumor response, confirmed by a scan no less than 4 weeks after the criteria for response were first met. Participants were evaluated for tumor response according to modified Response Evaluation Criteria in Solid Tumors (RECIST) based on the response assessment from a blinded review of radiographic scans by the Independent Review Committee. Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions. Partial Response (PR): disappearance of all target lesions, and persistence of one or more non-target lesion(s) not qualifying for either CR or progressive disease, or, at least a 30% decrease in the sum of the longest diameters (SLD) of target lesions, taking as reference the baseline SLD, with no progressive disease of non-target lesions.

Kaplan-Meier estimate of the median time from first confirmed objective tumor response to first observed progression of disease or death due to progression of disease (whichever comes first).

Time to response was defined as the time from randomization to first partial or complete response, subsequently confirmed ≥ 4 weeks after the criteria for response were first met.

Kaplan-Meier estimates of median time from randomization to disease progression or death due to disease progression (whichever occurs first)

Kaplan-Meier estimate of the median time from randomization to the date the decision was made to end treatment for any reason.

Kaplan-Meier estimate of the median time from randomization to date of first observed progression of disease or death due to progression of disease (whichever comes first) for those participants with a best response of stable disease. Stable disease defined as neither sufficient shrinkage to qualify for a partial response nor sufficient increase to qualify for progressive disease taking as reference the nadir longest diameter since the treatment started, no unequivocal progression of existing non-target lesions, and no new lesions.

The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Safety Analysis set includes all randomized patients, analyzed according to the treatment they actually received. Hence, 2 patients randomized to Panitumumab Plus BSC treatment group are analyzed in the BSC Alone group for safety.

Panitumumab plus best supportive care (BSC). Panitumumab was administered by intravenous infusion at a dose of 6 mg/kg once every 2 weeks until participants developed progressive disease or were unable to tolerate study drug.

Panitumumab Plus BSC

Best supportive care defined as the best care available as judged appropriate by the investigator and according to institutional guidelines, including antibiotics, analgesics, radiation therapy for pain control (limited to bone metastases), corticosteroids, transfusions, psychotherapy, growth factors, palliative surgery, or any symptomatic therapy as clinically indicated. For the purpose of this study, best supportive care does not include anti-neoplastic chemotherapy.

BSC Alone

Total

Age, Continuous

Sex: Female, Male

Japanese

Aborigine

Other

American Indian or Alaska Native

Asian

Native Hawaiian or Other Pacific Islander

Black or African American

White or Caucasian

Hispanic or Latino

Race/Ethnicity, Customized

Central and Eastern Europe

Western Europe

Rest of World

Central and Eastern Europe includes the Czech Republic, Greece, Hungary, and the Slovak Republic. Rest of World includes Australia, Canada and New Zealand. Western Europe includes Austria, Belgium, France, Germany, Italy, Portugal, Spain, Switzerland, and the Netherlands.

Region of Enrollment

0 or 1

Scale used to assess how a patient's disease is progressing, how the disease affects the daily living abilities of the patient: 0 = Fully active, able to carry on all pre-disease performance without restriction; 1 = Restricted in physically strenuous activity, ambulatory, able to carry out work of a light nature; 2 = Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about \> 50% of waking hours; 3 = Capable of only limited self care, confined to a bed or chair \> 50% of waking hours; 4 = Completely disabled, confined to bed or chair; 5 = Dead.

Eastern Cooperative Oncology Group (ECOG) performance status

Study Director

Null hypothesis was no difference between treatment groups

Progression-free Survival Time

Overall Survival

Objective Tumor Response

Intention-to-treat participants who had a confirmed objective tumor response. No objective tumor responses were observed in the BSC alone treatment arm.

Duration of Response

Intention-to-treat (ITT) participants who had a confirmed objective tumor response. No objective tumor responses were observed in the BSC alone treatment arm.

Time to Response

Time to Disease Progression

Time to Treatment Failure

Participants who had a best overall response of stable disease

Duration of Stable Disease

Kaplan-Meier estimates of median time from randomization to either death or first observed disease progression among participants with wild-type Kirsten Rat Sarcoma Virus Oncogene (KRAS) status. Participants were evaluated for tumor response according to modified Response Evaluation Criteria in Solid Tumors (RECIST) based on the response assessment from a blinded review of radiographic scans by the Independent Review Committee. Progressive disease defined as least a 20% increase in the sum of the longest diameters (SLD) of target lesions, taking as reference the nadir SLD recorded since the treatment started or the appearance of one or more new lesions, or the unequivocal progression of existing non-target lesions.

Panitumumab Plus Best Supportive Care

Wild-type KRAS Efficacy Analysis Set, a subset of the Intention-to-Treat set with wild-type Kirsten Rat Sarcoma Virus Oncogene (KRAS) status.

Progression-free Survival Time (Wild-type KRAS)

Kaplan-Meier estimates of median time from randomization to either death or first observed disease progression among participants with mutant Kirsten Rat Sarcoma Virus Oncogene (KRAS) status. Participants were evaluated for tumor response according to modified Response Evaluation Criteria in Solid Tumors (RECIST) based on the response assessment from a blinded review of radiographic scans by the Independent Review Committee. Progressive disease defined as least a 20% increase in the sum of the longest diameters (SLD) of target lesions, taking as reference the nadir SLD recorded since the treatment started or the appearance of one or more new lesions, or the unequivocal progression of existing non-target lesions.

Mutant KRAS Efficacy Analysis Set, a subset of the Intention-to-Treat set with mutant Kirsten Rat Sarcoma Virus Oncogene (KRAS) status.

Progression-free Survival Time (Mutant KRAS)

Overall Study

ABX-EGF

The purpose of this study is to examine the safety of ABX-EGF administered as monotherapy in subjects with metastatic colorectal cancer who were previously randomized to best supportive care (BSC) in protocol 20020408 and subsequently determined to have progressive disease.

Evaluating ABX-EGF Extended Therapy in Subjects With MetastaticColorectal Cancer

A Multicenter, Open-label, Single Arm Clinical Trial to Determine the Safety of ABX-EGF Extended Therapy in Subjects With Metastatic Colorectal Cancer

Micronutrients

Bevacizumab

Irinotecan

Leucovorin

Fluorouracil

Oxaliplatin

Endothelial Growth Factors

Angiogenesis Inhibitors

Growth Inhibitors

Topoisomerase I Inhibitors

Enzyme Inhibitors

Oxaliplatin-based chemotherapy and Bevacizumab Q2W alone.

Irinotecan-based chemotherapy and Bevacizumab Q2W plus panitumumab 6mg/kg Q2W

Irinotecan-based chemotherapy and Bevacizumab Q2W alone

Oxaliplatin-based chemotherapy and Bevacizumab Q2W plus panitumumab 6mg/kg Q2W

Oxaliplatin-based Chemotherapy Every 2 Week Regimens (Q2W Cycles) consisting of Oxaliplatin, Leucovorin (LV), 5-Fluorouracil (5-FU) - To be determined by physician. On Day 1 irinotecan and LV are given at the same time using different bags and a Y-line followed by 5-FU administration.

Oxaliplatin Based Chemotherapy

PanitumumabPanitumumab is a high affinity (Kd = 5 x 10-11 M) fully human IgG2 monoclonal antibody that is directed against the human EGFr. Panitumumab will be administered by a 30-60 minute IV infusion at a dose of 6 mg/kg once every 2 weeks on the same day of the oxaliplatin- or irinotecan-based chemotherapy and bevacizumab.

Irinotecan-based Chemotherapy Every 2 Week Regimens (Q2W Cycles) - Irinotecan, Leucovorin (LV), 5-Fluorouracil (5-FU) - To be determined by physician. On Day 1 irinotecan and LV are given at the same time using different bags and a Y-line followed by 5-FU administration.

Irinotecan Based Chemotherapy

Bevacizumab is a vascular endothelial growth factor (VEGF)-targeted antibody therapy that was administered to subjects intravenously Q2 weeks as per usual standard of care on the same day of chemotherapy and panitumumab administration .

The purpose of this study is to assess whether treatment with the study drug, panitumumab given concomitantly with every 2 (Q2) week oxaliplatin-based chemotherapy and bevacizumab improves progression-free survival (PFS) compared to treatment Q2-week with oxaliplatin-based chemotherapy and bevacizumab alone. All subjects will receive Q2-week oxaliplatin- or irinotecan-based chemotherapy and bevacizumab. Control arm subjects will not receive concomitant panitumumab therapy.

PACCE: Panitumumab Advanced Colorectal Cancer Evaluation Study

PACCE: A Randomized, Open-Label, Controlled, Clinical Trial of Chemotherapy and Bevacizumab With and Without Panitumumab in the First-Line Treatment of Subjects With Metastatic Colorectal Cancer

Kaplan-Meier estimate of the median time from randomization to death from any cause or first observed disease progression

Objective tumor response (complete or partial) rate through week 12 based on central review in the Irinotecan stratum

Kaplan-Meier estimate of the median time from randomization to death from any cause in groups treated with Oxaliplatin

Best overall response of complete or partial response within oxaliplatin stratum

Kaplan-Meier estimate of the median time from randomization to disease progression or death due to disease progression within the oxaliplatin stratum

Kaplan-Meier estimate of the median time from randomization to the date the decision was made to discontinue treatment for a reason other than a complete response to treatment within the oxaliplatin stratum.

Incidence of mortality from any cause in groups treated with Irinotecan. Incidence is provided in lieu of the median time to death since the median or its measure of dispersion was not estimable for at least one treatment arm.

Best overall response of complete or partial response within irinotecan stratum

Kaplan-Meier estimate of the median time from randomization to disease progression or death due to disease progression within the irinotecan stratum

Kaplan-Meier estimate of the median time from randomization to the date the decision was made to discontinue treatment for a reason other than a complete response to treatment within the irinotecan stratum

The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.

Panit. Plus Bevacizumab With Chemotherapy

Bevacizumab With Chemotherapy

Oxaliplatin-based chemotherapy and Bevacizumab Q2W alone

Oxaliplatin and Bevacizumab Without Panitumumab

Irinotecan-based chemotherapy and Bevacizumab Q2W plus panitumumab 6 mg/kg Q2W

Irinotecan and Bevacizumab Plus Panitumumab

Irinotecan and Bevacizumab Without Panitumumab

Oxaliplatin-based chemotherapy and Bevacizumab Q2W plus panitumumab 6 mg/kg Q2W

Oxaliplatin and Bevacizumab Plus Panitumumab

Eastern Cooperative Oncology Group (ECOG) Score

ECOG Score

None

Number of Metastatic Organs

Colon

Rectal

Primary Site of Disease

Prior adjuvant chemotherapy

Progression-Free Survival (Oxaliplatin)

Overall Survival (Oxaliplatin)

Objective Tumor Response Rate (Oxaliplatin)

Time to Progression (Oxaliplatin)

Time to Treatment Failure (Oxaliplatin)

Objective Tumor Response Through Week 12 (Irinotecan)

Overall Survival (Irinotecan)

Progression-free Survival (Irinotecan)

Kaplan-Meier estimate of the median time from randomization to death from any cause or first observed disease progression in groups treated with oxaliplatin and having a wild-type Kirsten Rat Sarcoma Virus Oncogene (KRAS)

Subset of the KRAS Efficacy Analysis Set, composed of participants from the intention-to-treat set who received at least 1 dose of first-line treatment and for whom KRAS mutation status was assessed as wild-type, who were treated with oxaliplatin

Progression-free Survival (Wild-type KRAS)

Kaplan-Meier estimate of the median time from randomization to death from any cause or first observed disease progression in groups treated with oxaliplatin and having a mutant Kirsten Rat Sarcoma Virus Oncogene (KRAS)

Subset of the KRAS Efficacy Analysis Set, composed of participants from the intention-to-treat set who received at least 1 dose of first-line treatment and for whom KRAS mutation status was assessed as mutant, who were treated with oxaliplatin

Progression-free Survival (Mutant KRAS)

Kaplan-Meier estimate of the median time from randomization to death from any cause in groups treated with Oxaliplatin and having a wild-type Kirsten Rat Sarcoma Virus Oncogene (KRAS). Since the measure of dispersion could not be estimated for at least one treatment arm, participant incidence is provided in lieu of the median

Overall Survival (Wild-type KRAS)

Kaplan-Meier estimate of the median time from randomization to death from any cause in groups treated with Oxaliplatin and having a mutant Kirsten Rat Sarcoma Virus Oncogene (KRAS). Since the measure of dispersion could not be estimated for at least one treatment arm, participant incidence is provided in lieu of the median.

Overall Survival (Mutant KRAS)

Best overall response of complete or partial response in participants treated with irinotecan and having a wild-type Kirsten Rat Sarcoma Virus Oncogene (KRAS)

Subset of the KRAS Efficacy Analysis Set, composed of participants from the intention-to-treat set who received at least 1 dose of first-line treatment and for whom KRAS mutation status was assessed as wild-type, who were treated with irinotecan

Objective Tumor Response Rate (Wild-type KRAS)

Best overall response of complete or partial response in participants treated with irinotecan and having a mutant Kirsten Rat Sarcoma Virus Oncogene (KRAS)

Subset of the KRAS Efficacy Analysis Set, composed of participants from the intention-to-treat set who received at least 1 dose of first-line treatment and for whom KRAS mutation status was assessed as mutant, who were treated with irinotecan

Objective Tumor Response Rate (Mutant KRAS)

Objective Tumor Response Rate (Irinotecan)

Time to Progression (Irinotecan)

Time to Treatment Failure (Irinotecan)

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.

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.

Panitumumab (ABX-EGF) Monotherapy in Patients With Metastatic Colorectal Cancer

A Phase 2 Multicenter Single Arm Clinical Trial of ABX-EGF Monotherapy in Subjects With Metastatic Colorectal Cancer Whose Tumors Express Low or Negative EGFr Levels of Immunohistochemistry Following Treatment With Fluoropyrimidine, Irinotecan, and Oxaliplatin Chemotherapy

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.

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.

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 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.

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.

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.

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.

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.

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.

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).

Objective Tumor Response Through Week 16

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.

Objective Tumor Response Throughout the Study

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.

Time to Initial Objective Response

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Two Dose Schedules of Panitumumab in Subjects With Advanced Solid Tumors	NCT00091806	Tumors Oncology Solid Tumors	panitumumab (AB... Panitumumab	18 Years -	Amgen
Evaluating Panitumumab (ABX-EGF) Plus Best Supportive Care Versus Best Supportive Care in Patients With Metastatic Colorectal Cancer	NCT00113763	Colorectal Canc... Metastases	Best supportive... Panitumumab	18 Years -	Amgen
Evaluating ABX-EGF Extended Therapy in Subjects With MetastaticColorectal Cancer	NCT00113776	Colorectal Canc...	ABX-EGF	18 Years -	Amgen
PACCE: Panitumumab Advanced Colorectal Cancer Evaluation Study	NCT00115765	Colorectal Canc...	Oxaliplatin Bas... Panitumumab Irinotecan Base... Bevacizumab	18 Years -	Amgen
Panitumumab (ABX-EGF) Monotherapy in Patients With Metastatic Colorectal Cancer	NCT00089635	Colorectal Canc... Metastases	Panitumumab	18 Years -	Amgen
Panitumumab (ABX-EGF) Monotherapy in Patients With Metastatic Colorectal Cancer	NCT00089635	Colorectal Canc... Metastases	Panitumumab	18 Years -	Amgen

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