Conatumumab/Panitumumab Combination Metastatic Colorectal Cancer Study

Colorectal Cancer Clinical Trial

Official title:

A Phase 1b/2 Trial of AMG 655 in Combination With Panitumumab in Subjects With Metastatic Colorectal Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00630786
• Other study ID #: 20060332
• Secondary ID: 2007-004722-25
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: February 28, 2008
• Last updated: February 5, 2014
• Start date: January 2008
• Est. completion date: November 2010

Study information

• Verified date: February 2014
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Public Service (FPS) Health, Food Chain Safety and EnvironmentEU: CHMPFrance: Ministry of HealthGermany: Federal Institute for Drugs and Medical DevicesUnited States: Food and Drug AdministrationUnited States: Institutional Review BoardUnited States: Western Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 53
• Est. completion date: November 2010
• Est. primary completion date: May 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colon Cancer
• Colorectal Cancer
• Colorectal Neoplasms
• Metastatic Colorectal Cancer
• Oncology
• Rectal Cancer

Intervention

Drug:
• Panitumumab
Administered by intravenous infusion
• Conatumumab
Administered by intravenous infusion

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	4 weeks	No
Primary	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.	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).	No
Secondary	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.	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).	No
Secondary	Overall Survival	Kaplan-Meier estimate of time from enrollment to death from any cause	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).	No
Secondary	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.	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).	No
Secondary	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.	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).	No
Secondary	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.	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).	No
Secondary	Number of Participants With Anti-therapeutic Antibodies	Number of participants with human anti-panitumumab antibodies (HAPA) or anti-conatumumab antibodies measured by immunoassay.	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.	No
Secondary	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.	From first dose of investigational drug until 30 days after the last dose, up to a maximum of 50 weeks.	No
Secondary	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.	From first dose of investigational drug until 30 days after the last dose, up to a maximum of 50 weeks.	No

External Links

•   AmgenTrials clinical trials website