Colon CancerPhase 1/2NCT00630786
Conatumumab/Panitumumab Combination Metastatic Colorectal Cancer Study
A Phase 1/2 study testing Panitumumab and Conatumumab in people with Colon Cancer and Colorectal Cancer, run by Amgen.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colon Cancer, Colorectal Cancer, Rectal Cancer
- What is being tested?
- Panitumumab and Conatumumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 53 participants
- Where
- No sites listed yet
- Study dates
- Jan 2008to Nov 2010
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 22Show fewer
- 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
Who cannot join
- 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
Show all 23Show fewer
- 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
About this study
Official title: A Phase 1b/2 Trial of AMG 655 in Combination With Panitumumab in Subjects With Metastatic Colorectal Cancer
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.
Read the 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).
- Being tested
- Panitumumab, Conatumumab
- Medical subject headings
- Colonic Neoplasms, Colorectal Neoplasms, Rectal Neoplasms, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PanitumumabDrug
Also called Vectibix®
Administered by intravenous infusion
ConatumumabDrug
Also called AMG 655
Administered by intravenous infusion
| Study group | Role | What they receive |
|---|---|---|
| Panitumumab plus conatumumab | Experimental | 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. Receives: Drug: Panitumumab; Drug: Conatumumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 4 weeks
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.
Measured: 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 outcomes (8)
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.
Measured: 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).
Overall Survival
Kaplan-Meier estimate of time from enrollment to death from any cause
Measured: 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).
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.
Measured: 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).
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.
Measured: 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).
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.
Measured: 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).
Number of Participants With Anti-therapeutic Antibodies
Number of participants with human anti-panitumumab antibodies (HAPA) or anti-conatumumab antibodies measured by immunoassay.
Measured: 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.
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.
Measured: From first dose of investigational drug until 30 days after the last dose, up to a maximum of 50 weeks.
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.
Measured: From first dose of investigational drug until 30 days after the last dose, up to a maximum of 50 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2008 (estimated)
- Study startJan 2008
- Primary completionMay 2009
- Study completionNov 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Colon CancerStudies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 53 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00630786
- Sponsor's protocol ID
- 20060332
- Other IDs
- 2007-004722-25
- Status last verified
- Feb 2014
- First submitted
- 28 Feb 2008
- Last updated
- 6 Feb 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b/2 Trial of AMG 655 in Combination With Panitumumab in Subjects With Metastatic Colorectal Cancer
- ClinicalTrials.gov ID
- NCT00630786
- Acronym / sponsor ID
- 20060332
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 53 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- Jan 2008
- Primary completion
- May 2009 (actual)
- Study completion
- Nov 2010 (actual)
- First posted
- 7 Mar 2008 (estimated)
- Results
- Posted 6 Feb 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Panitumumab plus conatumumab | Experimental | Drug: Panitumumab, Drug: ConatumumabParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- 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
Key exclusion criteria (23 listed)
- History of other primary cancer, unless:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PanitumumabAlso: Vectibix®Administered by intravenous infusion | Drug | Panitumumab plus conatumumab |
| ConatumumabAlso: AMG 655Administered by intravenous infusion | Drug | Panitumumab plus conatumumab |
Primary outcome
Part 1: Number of Participants With Dose-limiting Toxicities
Time frame: 4 weeks
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
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).
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.
8 secondary outcomes
Progression-free Survival
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).
Overall Survival
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).
Number of Participants With Disease Control
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).
Time to 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).
Duation of 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).
Number of Participants With Anti-therapeutic Antibodies
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.
Number of Participants With Adverse Events (AEs)
Time frame: From first dose of investigational drug until 30 days after the last dose, up to a maximum of 50 weeks.
Number of Participants With Post-baseline Laboratory Values Grade 3 or Higher
Time frame: From first dose of investigational drug until 30 days after the last dose, up to a maximum of 50 weeks.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- AmgenTrials clinical trials websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD study director
Amgen
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Panitumumab and Conatumumab in people with Colon Cancer and Colorectal Cancer, run by Amgen.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Feb 2014. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Feb 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part 1: Number of Participants With Dose-limiting Toxicities (time frame: 4 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2014.