Conatumumab/Panitumumab Combination Metastatic Colorectal Cancer Study
Primary Purpose
Colon Cancer, Colorectal Cancer, Rectal Cancer
Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Panitumumab
Conatumumab
Sponsored by
About this trial
This is an interventional treatment trial for Colon Cancer
Eligibility Criteria
Inclusion Criteria:
- Histologically or cytologically confirmed metastatic adenocarcinoma of the colon or rectum
- Radiographically documented disease progression per modified Response Evaluation Criteria in Solid Tumors (RECIST) during or following treatment with fluoropyrimidine, irinotecan, and/or oxaliplatin chemotherapy for Metastatic Colorectal Cancer. Progressive disease must be documented during or ≤ 6 months after the last dose of the most recent chemotherapy regimen prior to enrollment.
- At least 1 uni-dimensionally measurable lesion measuring ≥ 20 mm in one dimension per modified RECIST. Lesion must not be chosen from a previously irradiated field, unless there has been documented disease progression in that field after irradiation and prior to enrollment. All sites of disease must be evaluated.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Available archived paraffin-embedded tumor tissue from the primary tumor or metastasis for submission to the central laboratory
- Man or woman ≥ 18 years of age at the time of enrollment
Hematologic function within the following limits:
- Absolute neutrophil count (ANC) > 1.0 x 10^9 cells/L
- Platelets ≥ 100 x 10^9/L
Renal function within the following limits:
- Creatinine < 2.0 mg/dL
Hepatic function within the following limits:
- Aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normal (ULN) (≤ 5 x ULN if liver metastases)
- Alanine aminotransferase (ALT) ≤ 2.5 x ULN (≤ 5 x ULN if liver metastases)
- Bilirubin ≤ 2 x ULN
Metabolic function within the following limits:
- Amylase ≤ 2 x ULN
- Lipase ≤ 2 x ULN
- Magnesium ≥ lower limit of normal
- Negative pregnancy test ≤ 72 hours before enrollment (for woman of childbearing potential only)
- Must have received 1, 2, or 3 prior chemotherapy regimens for Metastatic Colorectal Cancer
- Competent to comprehend, sign, and date the independent ethics committee/institutional review board (IEC/IRB) approved written informed consent
Exclusion Criteria:
History of other primary cancer, unless:
- Curatively resected non-melanomatous skin cancer
- Curatively treated cervical carcinoma in situ
- Other primary solid tumor curatively treated with no known active disease present and no treatment administered for ≥ 5 years before enrollment
- Prior treatment with anti-epidermal growth factor receptor (EGFr) inhibitors (eg, cetuximab, erlotinib, gefitinib), unless treatment was received in the adjuvant setting ≥ 6 months before enrollment
- Use of systemic chemotherapy and radiotherapy ≤ 30 days before enrollment
- Use of prior anti-tumor therapies with a short serum half-life (less than 1 week) including prior experimental agents or approved anti-tumor small molecules ≤ 30 days before enrollment
- Use of anti-tumor therapies with a longer serum half-life (eg, bevacizumab) including prior experimental or approved protein/antibodies ≤ 42 days before enrollment
- Any investigational agent or therapy ≤ 30 days before enrollment
- Known allergy or hypersensitivity to any component of panitumumab and/or AMG 655
- History of or known presence of central nervous system (CNS) metastases
- History of interstitial lung disease (eg, pneumonitis, pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest computerized tomography (CT) scan
- Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤ 1 year before enrollment
- Active inflammatory bowel disease or other active bowel disease causing chronic diarrhea (defined as ≥ Common Terminology Criteria for Adverse Events [CTCAE] grade 2 [CTCAE version 3.0])
- Known positive test for human immunodeficiency virus (HIV) infection, hepatitis C virus, acute or chronic hepatitis B infection
- Any co-morbid disease or condition that could increase the risk of toxicity (eg, significant ascites, significant pleural effusion)
- Any uncontrolled concurrent illness (eg, infection, bleeding) or history of any medical condition that may interfere with the interpretation of the study results
- Major surgical procedure (requiring general anesthesia) ≤ 28 days or minor surgical procedure (excluding central venous catheter placement) ≤ 14 days before enrollment. Patients must have recovered from surgery related toxicities.
- Other investigational procedures are excluded
- Patient is currently pregnant or breast feeding
- Man or woman of childbearing potential who is not willing to use adequate contraceptive precautions during treatment and for 6 months (for women) or 1 month (for men) after the last investigational product administration. Adequate contraceptive precautions includes double barrier contraceptive methods (eg, diaphragm and condom) or abstinence.
- Previously enrolled into this study
- Patient unwilling or unable to comply with study requirements
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Panitumumab plus conatumumab
Arm Description
Participants received 10 mg/kg conatumumab and 6 mg/kg panitumumab administered on the same day by sequential intravenous (IV) infusions once every 2 weeks until progressive disease, intolerability, withdrawal, or death.
Outcomes
Primary Outcome Measures
Part 1: Number of Participants With Dose-limiting Toxicities
A dose-limiting toxicity (DLT) was defined as any grade 3 or 4 conatumumab-related or combination (panitumumab and conatumumab)-related adverse event, or grade 3 or 4 laboratory abnormality that occurred during the first 4 weeks (28 days) of treatment with panitumumab and conatumumab. Anemia and lymphopenia were not considered DLTs.
Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was used to grade all adverse events and toxicities.
Number of Participants With an Objective Response
An overall objective response of either a confirmed complete response or partial response, where the overall objective response was equivalent to the best overall response recorded for each participant from enrollment until disease progression or recurrence. Tumor response was assessed by the investigator according to the modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0. Responses were confirmed no less than 4 weeks after the criteria for response were first met. Complete response defined as the disappearance of all target and non-target lesions and no new lesions. Partial response defined as either the disappearance of all target lesions with the persistence of one or more non-target lesion(s), or, at least a 30% decrease in the sum of the longest diameter (SLD) of target lesions, taking as reference the Baseline SLD and the disappearance of all or the persistence of 1 or more non-target lesions.
Secondary Outcome Measures
Progression-free Survival
Kaplan-Meier estimate of the median time from enrollment to death from any cause or disease progression. Progressive disease is defined as at 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.
Overall Survival
Kaplan-Meier estimate of time from enrollment to death from any cause
Number of Participants With Disease Control
Disease control defined as participants with an overall objective response of complete response (CR), partial response (PR), or stable disease during the treatment period, assessed by the investigator according to the modified Response Evaluation Criteria in Solid Tumors (RECIST). Responses were confirmed no less than 4 weeks after the criteria for response were first met. CR defined as the disappearance of all target and non-target lesions and no new lesions. PR defined as either the disappearance of all target lesions with the persistence of one or more non-target lesion(s), or, at least a 30% decrease in the sum of the longest diameter (SLD) of target lesions, taking as reference the Baseline SLD and the disappearance of all or the persistence of 1 or more non-target lesions. Stable disease defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the nadir LD since the treatment started.
Time to Response
The interval in days from the first dose of study therapy to the date of first confirmed objective response. Calculated only for participants with an objective response.
Duation of Response
The interval in days from the first confirmed objective response to disease progression per the modified RECIST criteria or death. Calculated only for participants with an objective response.
Number of Participants With Anti-therapeutic Antibodies
Number of participants with human anti-panitumumab antibodies (HAPA) or anti-conatumumab antibodies measured by immunoassay.
Number of Participants With Adverse Events (AEs)
An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment, and includes any such occurrence (eg, sign, symptom, or diagnosis) or worsening of a pre-existing medical condition from the time that a participant has signed informed consent to the time of initiation of investigational product. The severity of AEs was graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, according to the following:
= Mild: Aware of sign or symptom, but easily tolerated
= Moderate: Discomfort enough to cause interference with usual activity;
= Severe: Incapacitating with inability to work or do usual activity;
= Life-threatening: an event in which the patient was, in the view of the investigator, at risk of death at the time of the event;
= Fatal.
Number of Participants With Post-baseline Laboratory Values Grade 3 or Higher
Laboratory values were assessed using the National Cancer Institute (NCI) Common Toxicity Criteria (version 3.0) according to the following: 1 = Mild; 2 = Moderate; 3 = Severe; 4 = Life-threatening; 5 = Fatal.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00630786
Brief Title
Conatumumab/Panitumumab Combination Metastatic Colorectal Cancer Study
Official Title
A Phase 1b/2 Trial of AMG 655 in Combination With Panitumumab in Subjects With Metastatic Colorectal Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
February 2014
Overall Recruitment Status
Completed
Study Start Date
January 2008 (undefined)
Primary Completion Date
May 2009 (Actual)
Study Completion Date
November 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is an exploratory phase 1b/2, global, multicenter, single-arm, 2-part (phase 1b and 2) study of conatumumab in combination with panitumumab in patients with Metastatic Colorectal Cancer.
Detailed Description
This is an exploratory phase 1b/2, global, multicenter, single-arm, 2-part (phase 1b and 2) study of conatumumab in combination with panitumumab in patients with Metastatic Colorectal Cancer.
The objective for Part 1 is to identify a tolerable dose of conatumumab in combination with panitumumab based on the incidence of dose-limiting toxicities in patients with Metastatic Colorectal Cancer.
The objective for Part 2 is to evaluate the objective response rate stratified by Kirsten Rat Sarcoma Virus Oncogene (KRAS) status (wild-type versus mutant) in patients with Metastatic Colorectal Cancer treated with the combination of panitumumab and conatumumab (tolerable dose identified in part 1).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colon Cancer, Colorectal Cancer, Rectal Cancer, Metastatic Colorectal Cancer, Oncology
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
53 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Panitumumab plus conatumumab
Arm Type
Experimental
Arm Description
Participants received 10 mg/kg conatumumab and 6 mg/kg panitumumab administered on the same day by sequential intravenous (IV) infusions once every 2 weeks until progressive disease, intolerability, withdrawal, or death.
Intervention Type
Drug
Intervention Name(s)
Panitumumab
Other Intervention Name(s)
Vectibix®
Intervention Description
Administered by intravenous infusion
Intervention Type
Drug
Intervention Name(s)
Conatumumab
Other Intervention Name(s)
AMG 655
Intervention Description
Administered by intravenous infusion
Primary Outcome Measure Information:
Title
Part 1: Number of Participants With Dose-limiting Toxicities
Description
A dose-limiting toxicity (DLT) was defined as any grade 3 or 4 conatumumab-related or combination (panitumumab and conatumumab)-related adverse event, or grade 3 or 4 laboratory abnormality that occurred during the first 4 weeks (28 days) of treatment with panitumumab and conatumumab. Anemia and lymphopenia were not considered DLTs.
Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was used to grade all adverse events and toxicities.
Time Frame
4 weeks
Title
Number of Participants With an Objective Response
Description
An overall objective response of either a confirmed complete response or partial response, where the overall objective response was equivalent to the best overall response recorded for each participant from enrollment until disease progression or recurrence. Tumor response was assessed by the investigator according to the modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0. Responses were confirmed no less than 4 weeks after the criteria for response were first met. Complete response defined as the disappearance of all target and non-target lesions and no new lesions. Partial response defined as either the disappearance of all target lesions with the persistence of one or more non-target lesion(s), or, at least a 30% decrease in the sum of the longest diameter (SLD) of target lesions, taking as reference the Baseline SLD and the disappearance of all or the persistence of 1 or more non-target lesions.
Time Frame
Participants were evaluated for tumor response until radiographic disease progression or until the participant began another anticancer treatment (up to a maximum of 55.6 weeks).
Secondary Outcome Measure Information:
Title
Progression-free Survival
Description
Kaplan-Meier estimate of the median time from enrollment to death from any cause or disease progression. Progressive disease is defined as at 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.
Time Frame
Participants were evaluated for tumor response until radiographic disease progression or until the participant began another anticancer treatment (up to a maximum of 55.6 weeks).
Title
Overall Survival
Description
Kaplan-Meier estimate of time from enrollment to death from any cause
Time Frame
Participants were evaluated for tumor response until radiographic disease progression or until the participant began another anticancer treatment (up to a maximum of 55.6 weeks).
Title
Number of Participants With Disease Control
Description
Disease control defined as participants with an overall objective response of complete response (CR), partial response (PR), or stable disease during the treatment period, assessed by the investigator according to the modified Response Evaluation Criteria in Solid Tumors (RECIST). Responses were confirmed no less than 4 weeks after the criteria for response were first met. CR defined as the disappearance of all target and non-target lesions and no new lesions. PR defined as either the disappearance of all target lesions with the persistence of one or more non-target lesion(s), or, at least a 30% decrease in the sum of the longest diameter (SLD) of target lesions, taking as reference the Baseline SLD and the disappearance of all or the persistence of 1 or more non-target lesions. Stable disease defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the nadir LD since the treatment started.
Time Frame
Participants were evaluated for tumor response until radiographic disease progression or until the participant began another anticancer treatment (up to a maximum of 55.6 weeks).
Title
Time to Response
Description
The interval in days from the first dose of study therapy to the date of first confirmed objective response. Calculated only for participants with an objective response.
Time Frame
Participants were evaluated for tumor response until radiographic disease progression or until the participant began another anticancer treatment (up to a maximum of 55.6 weeks).
Title
Duation of Response
Description
The interval in days from the first confirmed objective response to disease progression per the modified RECIST criteria or death. Calculated only for participants with an objective response.
Time Frame
Participants were evaluated for tumor response until radiographic disease progression or until the participant began another anticancer treatment (up to a maximum of 55.6 weeks).
Title
Number of Participants With Anti-therapeutic Antibodies
Description
Number of participants with human anti-panitumumab antibodies (HAPA) or anti-conatumumab antibodies measured by immunoassay.
Time Frame
Antibody samples were collected at weeks 1, 7, and 23 and every 6 months thereafter during treatment, and at the safety follow-up and follow-up visits. The mean follow-up time was 35.7 weeks.
Title
Number of Participants With Adverse Events (AEs)
Description
An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment, and includes any such occurrence (eg, sign, symptom, or diagnosis) or worsening of a pre-existing medical condition from the time that a participant has signed informed consent to the time of initiation of investigational product. The severity of AEs was graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, according to the following:
= Mild: Aware of sign or symptom, but easily tolerated
= Moderate: Discomfort enough to cause interference with usual activity;
= Severe: Incapacitating with inability to work or do usual activity;
= Life-threatening: an event in which the patient was, in the view of the investigator, at risk of death at the time of the event;
= Fatal.
Time Frame
From first dose of investigational drug until 30 days after the last dose, up to a maximum of 50 weeks.
Title
Number of Participants With Post-baseline Laboratory Values Grade 3 or Higher
Description
Laboratory values were assessed using the National Cancer Institute (NCI) Common Toxicity Criteria (version 3.0) according to the following: 1 = Mild; 2 = Moderate; 3 = Severe; 4 = Life-threatening; 5 = Fatal.
Time Frame
From first dose of investigational drug until 30 days after the last dose, up to a maximum of 50 weeks.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically or cytologically confirmed metastatic adenocarcinoma of the colon or rectum
Radiographically documented disease progression per modified Response Evaluation Criteria in Solid Tumors (RECIST) during or following treatment with fluoropyrimidine, irinotecan, and/or oxaliplatin chemotherapy for Metastatic Colorectal Cancer. Progressive disease must be documented during or ≤ 6 months after the last dose of the most recent chemotherapy regimen prior to enrollment.
At least 1 uni-dimensionally measurable lesion measuring ≥ 20 mm in one dimension per modified RECIST. Lesion must not be chosen from a previously irradiated field, unless there has been documented disease progression in that field after irradiation and prior to enrollment. All sites of disease must be evaluated.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Available archived paraffin-embedded tumor tissue from the primary tumor or metastasis for submission to the central laboratory
Man or woman ≥ 18 years of age at the time of enrollment
Hematologic function within the following limits:
Absolute neutrophil count (ANC) > 1.0 x 10^9 cells/L
Platelets ≥ 100 x 10^9/L
Renal function within the following limits:
Creatinine < 2.0 mg/dL
Hepatic function within the following limits:
Aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normal (ULN) (≤ 5 x ULN if liver metastases)
Alanine aminotransferase (ALT) ≤ 2.5 x ULN (≤ 5 x ULN if liver metastases)
Bilirubin ≤ 2 x ULN
Metabolic function within the following limits:
Amylase ≤ 2 x ULN
Lipase ≤ 2 x ULN
Magnesium ≥ lower limit of normal
Negative pregnancy test ≤ 72 hours before enrollment (for woman of childbearing potential only)
Must have received 1, 2, or 3 prior chemotherapy regimens for Metastatic Colorectal Cancer
Competent to comprehend, sign, and date the independent ethics committee/institutional review board (IEC/IRB) approved written informed consent
Exclusion Criteria:
History of other primary cancer, unless:
Curatively resected non-melanomatous skin cancer
Curatively treated cervical carcinoma in situ
Other primary solid tumor curatively treated with no known active disease present and no treatment administered for ≥ 5 years before enrollment
Prior treatment with anti-epidermal growth factor receptor (EGFr) inhibitors (eg, cetuximab, erlotinib, gefitinib), unless treatment was received in the adjuvant setting ≥ 6 months before enrollment
Use of systemic chemotherapy and radiotherapy ≤ 30 days before enrollment
Use of prior anti-tumor therapies with a short serum half-life (less than 1 week) including prior experimental agents or approved anti-tumor small molecules ≤ 30 days before enrollment
Use of anti-tumor therapies with a longer serum half-life (eg, bevacizumab) including prior experimental or approved protein/antibodies ≤ 42 days before enrollment
Any investigational agent or therapy ≤ 30 days before enrollment
Known allergy or hypersensitivity to any component of panitumumab and/or AMG 655
History of or known presence of central nervous system (CNS) metastases
History of interstitial lung disease (eg, pneumonitis, pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest computerized tomography (CT) scan
Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤ 1 year before enrollment
Active inflammatory bowel disease or other active bowel disease causing chronic diarrhea (defined as ≥ Common Terminology Criteria for Adverse Events [CTCAE] grade 2 [CTCAE version 3.0])
Known positive test for human immunodeficiency virus (HIV) infection, hepatitis C virus, acute or chronic hepatitis B infection
Any co-morbid disease or condition that could increase the risk of toxicity (eg, significant ascites, significant pleural effusion)
Any uncontrolled concurrent illness (eg, infection, bleeding) or history of any medical condition that may interfere with the interpretation of the study results
Major surgical procedure (requiring general anesthesia) ≤ 28 days or minor surgical procedure (excluding central venous catheter placement) ≤ 14 days before enrollment. Patients must have recovered from surgery related toxicities.
Other investigational procedures are excluded
Patient is currently pregnant or breast feeding
Man or woman of childbearing potential who is not willing to use adequate contraceptive precautions during treatment and for 6 months (for women) or 1 month (for men) after the last investigational product administration. Adequate contraceptive precautions includes double barrier contraceptive methods (eg, diaphragm and condom) or abstinence.
Previously enrolled into this study
Patient unwilling or unable to comply with study requirements
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD
Organizational Affiliation
Amgen
Official's Role
Study Director
12. IPD Sharing Statement
Links:
URL
http://download.veritasmedicine.com/REGFILES/amgen/Amgen_results_disclaimer.pdf
Description
Notice regarding posted summaries of trial results
URL
http://www.amgentrials.com
Description
AmgenTrials clinical trials website
Learn more about this trial
Conatumumab/Panitumumab Combination Metastatic Colorectal Cancer Study
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