Trial Outcomes & Findings for Erbitux (Cetuximab) Given Alone to Patients With EGFR-Negative Metastatic Colon or Rectal Cancer That is Refractory to Chemotherapy (NCT NCT00083720)
NCT ID: NCT00083720
Last Updated: 2011-05-25
Results Overview
Determine the response rate (complete response \[CR\] and partial response \[PR\]) in patients with epidermal growth factor receptor (EGFR)-negative metastatic colorectal carcinoma treated with cetuximab, as classified by the investigator according to the World Health Organization (WHO) criteria. The calculation was the total number of patients with CR or PR divided by the total number of patients treated.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
87 participants
Primary outcome timeframe
Tumor evaluations were performed at a minimum every 6 weeks while on cetuximab therapy until progressive disease (PD) or recurrence. Patients with a PR or CR had a confirmatory tumor assessment no less than 4 weeks after the initial evaluation.
Results posted on
2011-05-25
Participant Flow
A total of 87 patients were enrolled between 22 Oct 2004 and 20 Aug 2007 at nine sites in the USA and four sites in Canada.
Participant milestones
| Measure |
Cetuximab
Initial dose of 400 mg/m2 i.v. over 120 minutes, followed by 250 mg/m2 weekly i.v. over 60 minutes
|
|---|---|
|
Overall Study
STARTED
|
85
|
|
Overall Study
COMPLETED
|
85
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Erbitux (Cetuximab) Given Alone to Patients With EGFR-Negative Metastatic Colon or Rectal Cancer That is Refractory to Chemotherapy
Baseline characteristics by cohort
| Measure |
Cetuximab
n=85 Participants
Initial dose of 400 mg/m2 i.v. over 120 minutes, followed by 250 mg/m2 weekly i.v. over 60 minutes
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
42 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
43 Participants
n=5 Participants
|
|
Age Continuous
|
64.2 years
STANDARD_DEVIATION 11.41 • n=5 Participants
|
|
Sex: Female, Male
Female
|
26 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
59 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
20 participants
n=5 Participants
|
|
Region of Enrollment
Canada
|
65 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Tumor evaluations were performed at a minimum every 6 weeks while on cetuximab therapy until progressive disease (PD) or recurrence. Patients with a PR or CR had a confirmatory tumor assessment no less than 4 weeks after the initial evaluation.Population: The overall response rate was calculated for the modified Intent to Treat (mITT) population.
Determine the response rate (complete response \[CR\] and partial response \[PR\]) in patients with epidermal growth factor receptor (EGFR)-negative metastatic colorectal carcinoma treated with cetuximab, as classified by the investigator according to the World Health Organization (WHO) criteria. The calculation was the total number of patients with CR or PR divided by the total number of patients treated.
Outcome measures
| Measure |
Cetuximab
n=85 Participants
Initial dose of 400 mg/m2 i.v. over 120 minutes, followed by 250 mg/m2 weekly i.v. over 60 minutes
|
|---|---|
|
Percentage of Participants With an Overall Resonse
|
8.2 percentage of participants
Interval 3.4 to 16.2
|
PRIMARY outcome
Timeframe: An adverse event (AE) was included in the safety analysis if its onset date occurred anytime during cetuximab treatment or up to 30 days after the last dose of cetuximab.Population: Patients who were enrolled and treated with any quantity of cetuximab constitute the mITT population. Since this trial was a single arm trial, the mITT population used for the efficacy analyses was also used for the safety analyses.
Reported adverse events (AEs) per patient were coded according to the corresponding preferred term and system organ class in the Medical Dictionary for Regulatory Activities dictionary. The National Cancer Insititute-Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 3.0 was used to grade all AEs. The collection of AEs began at the time the patient received the first cetuximab dose and continued during the study until 30 days after the last dose of cetuximab. All patients who were enrolled and treated with cetuximab were assessed for safety (mITT population, as treated).
Outcome measures
| Measure |
Cetuximab
n=85 Participants
Initial dose of 400 mg/m2 i.v. over 120 minutes, followed by 250 mg/m2 weekly i.v. over 60 minutes
|
|---|---|
|
Number of Participants With Adverse Events
|
85 Participants
|
PRIMARY outcome
Timeframe: A serious adverse event (SAE) was included in the safety analysis if its onset date occurred anytime during cetuximab treatment or up to 30 days after the last dose of cetuximab.Population: Patients who were enrolled and treated with any quantity of cetuximab constitute the mITT population. Since this trial was a single arm trial, the mITT population used for the efficacy analyses was also used for the safety analyses.
Reported SAEs per patient were coded according to the corresponding preferred term and system organ class in the Medical Dictionary for Regulatory Activities. The NCI-CTCAE Version 3.0 was used to grade all SAEs. An SAE was any untoward medical occurrence that resulted in death, persistent/significant disability/incapacity, was life threatening, required inpatient hospitalization or caused prolongation of existing hospitalization,congenital anomaly/birth defect, or any important medical event.
Outcome measures
| Measure |
Cetuximab
n=85 Participants
Initial dose of 400 mg/m2 i.v. over 120 minutes, followed by 250 mg/m2 weekly i.v. over 60 minutes
|
|---|---|
|
Number of Participants With Serious Adverse Events
|
19 Participants
|
SECONDARY outcome
Timeframe: Tumor evaluations were performed at a minimum of every 6 weeks while on cetuximab therapy. Patients with a PR or CR had a confirmatory tumor assessment no less than 4 weeks after the initial evaluation demonstrating a response.Population: Disease control rate was the total number of patients with best overall response of CR, PR and SD divided by the total number of patients treated.
This is the total number of patients with a best overall response of CR, PR, and stable disease (SD) divided by the total number of patients treated.
Outcome measures
| Measure |
Cetuximab
n=85 Participants
Initial dose of 400 mg/m2 i.v. over 120 minutes, followed by 250 mg/m2 weekly i.v. over 60 minutes
|
|---|---|
|
Percentage of Participants With Disease Control (CR, PR, or SD)
|
49.4 Percentage of participants
Interval 38.4 to 60.5
|
SECONDARY outcome
Timeframe: The duration of response was measured from the date of response to the first date of PD (range 2 to 7 months).Population: The duration of response was calculated for the subgroup of the mITT population who demonstrated a response.
In patients with a best overall response of CR or PR, the duration of response is measured from the date criteria are first met for CR or PR, until the first date that Progressive Disease (PD) is objectively documented or death occurs. Duration of response of living patients with no evidence of PD was censored on the date of their last tumor assessment.
Outcome measures
| Measure |
Cetuximab
n=7 Participants
Initial dose of 400 mg/m2 i.v. over 120 minutes, followed by 250 mg/m2 weekly i.v. over 60 minutes
|
|---|---|
|
Duration of Response
|
5.1 Months
Interval 2.7 to 6.9
|
SECONDARY outcome
Timeframe: Patients with PD after receiving at least one standard chemotherapeutic regimen that included a fluoropyrimidine (range: 1-3 months).Population: This measure was calculated for the mITT population.
This measure was defined as the time from the first day of treatment until the date of PD. Deaths without objective progression were censored. Patients who did not progress were censored at their last day of tumor assessment.
Outcome measures
| Measure |
Cetuximab
n=85 Participants
Initial dose of 400 mg/m2 i.v. over 120 minutes, followed by 250 mg/m2 weekly i.v. over 60 minutes
|
|---|---|
|
Time to Progression
|
2.5 Months
Interval 1.3 to 2.8
|
SECONDARY outcome
Timeframe: Survival information was collected every 3 months after completion of therapy and/or follow-up up to 24 months.Population: Overall survival was calculated from the time of the first day of therapy to the date of death for the mITT population.
This measure is defined as the time from the first day of therapy to the date of death. Survival of living patients or those lost to follow-up were censored on the last date the patients were known to be alive.
Outcome measures
| Measure |
Cetuximab
n=85 Participants
Initial dose of 400 mg/m2 i.v. over 120 minutes, followed by 250 mg/m2 weekly i.v. over 60 minutes
|
|---|---|
|
Overall Survival
|
10.0 Months
Interval 7.5 to 12.0
|
Adverse Events
Cetuximab
Serious events: 19 serious events
Other events: 84 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Cetuximab
n=85 participants at risk
Initial dose of 400 mg/m2 i.v. over 120 minutes, followed by 250 mg/m2 weekly i.v. over 60 minutes
|
|---|---|
|
Gastrointestinal disorders
Diarrhea
|
1.2%
1/85 • Number of events 1 • Adverse events were collected from the time that the patient received the initial cetuximab infusion and continued during the study until 30 days after the last dose of cetuximab.
The NCI-CTCAE V3.0 toxicity criteria was used to grading the severity of all AEs.
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
1.2%
1/85 • Number of events 2 • Adverse events were collected from the time that the patient received the initial cetuximab infusion and continued during the study until 30 days after the last dose of cetuximab.
The NCI-CTCAE V3.0 toxicity criteria was used to grading the severity of all AEs.
|
|
Gastrointestinal disorders
Intestinal obstruction
|
1.2%
1/85 • Number of events 1 • Adverse events were collected from the time that the patient received the initial cetuximab infusion and continued during the study until 30 days after the last dose of cetuximab.
The NCI-CTCAE V3.0 toxicity criteria was used to grading the severity of all AEs.
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
1.2%
1/85 • Number of events 1 • Adverse events were collected from the time that the patient received the initial cetuximab infusion and continued during the study until 30 days after the last dose of cetuximab.
The NCI-CTCAE V3.0 toxicity criteria was used to grading the severity of all AEs.
|
|
General disorders
Disease progression
|
3.5%
3/85 • Number of events 3 • Adverse events were collected from the time that the patient received the initial cetuximab infusion and continued during the study until 30 days after the last dose of cetuximab.
The NCI-CTCAE V3.0 toxicity criteria was used to grading the severity of all AEs.
|
|
General disorders
Death
|
1.2%
1/85 • Number of events 1 • Adverse events were collected from the time that the patient received the initial cetuximab infusion and continued during the study until 30 days after the last dose of cetuximab.
The NCI-CTCAE V3.0 toxicity criteria was used to grading the severity of all AEs.
|
|
General disorders
Infusion related reaction
|
1.2%
1/85 • Number of events 1 • Adverse events were collected from the time that the patient received the initial cetuximab infusion and continued during the study until 30 days after the last dose of cetuximab.
The NCI-CTCAE V3.0 toxicity criteria was used to grading the severity of all AEs.
|
|
General disorders
Pyrexia
|
1.2%
1/85 • Number of events 1 • Adverse events were collected from the time that the patient received the initial cetuximab infusion and continued during the study until 30 days after the last dose of cetuximab.
The NCI-CTCAE V3.0 toxicity criteria was used to grading the severity of all AEs.
|
|
Immune system disorders
Anaphylactic reaction
|
1.2%
1/85 • Number of events 1 • Adverse events were collected from the time that the patient received the initial cetuximab infusion and continued during the study until 30 days after the last dose of cetuximab.
The NCI-CTCAE V3.0 toxicity criteria was used to grading the severity of all AEs.
|
|
Immune system disorders
Hypersensitivity
|
1.2%
1/85 • Number of events 1 • Adverse events were collected from the time that the patient received the initial cetuximab infusion and continued during the study until 30 days after the last dose of cetuximab.
The NCI-CTCAE V3.0 toxicity criteria was used to grading the severity of all AEs.
|
|
Immune system disorders
Serum sickness
|
1.2%
1/85 • Number of events 1 • Adverse events were collected from the time that the patient received the initial cetuximab infusion and continued during the study until 30 days after the last dose of cetuximab.
The NCI-CTCAE V3.0 toxicity criteria was used to grading the severity of all AEs.
|
|
Infections and infestations
Catheter site infection
|
1.2%
1/85 • Number of events 1 • Adverse events were collected from the time that the patient received the initial cetuximab infusion and continued during the study until 30 days after the last dose of cetuximab.
The NCI-CTCAE V3.0 toxicity criteria was used to grading the severity of all AEs.
|
|
Infections and infestations
Cellulitis
|
1.2%
1/85 • Number of events 1 • Adverse events were collected from the time that the patient received the initial cetuximab infusion and continued during the study until 30 days after the last dose of cetuximab.
The NCI-CTCAE V3.0 toxicity criteria was used to grading the severity of all AEs.
|
|
Infections and infestations
Sepsis
|
1.2%
1/85 • Number of events 1 • Adverse events were collected from the time that the patient received the initial cetuximab infusion and continued during the study until 30 days after the last dose of cetuximab.
The NCI-CTCAE V3.0 toxicity criteria was used to grading the severity of all AEs.
|
|
Infections and infestations
Staphylococcal infection
|
1.2%
1/85 • Number of events 1 • Adverse events were collected from the time that the patient received the initial cetuximab infusion and continued during the study until 30 days after the last dose of cetuximab.
The NCI-CTCAE V3.0 toxicity criteria was used to grading the severity of all AEs.
|
|
Investigations
Blood magnesium decreased
|
1.2%
1/85 • Number of events 1 • Adverse events were collected from the time that the patient received the initial cetuximab infusion and continued during the study until 30 days after the last dose of cetuximab.
The NCI-CTCAE V3.0 toxicity criteria was used to grading the severity of all AEs.
|
|
Metabolism and nutrition disorders
Gout
|
1.2%
1/85 • Number of events 1 • Adverse events were collected from the time that the patient received the initial cetuximab infusion and continued during the study until 30 days after the last dose of cetuximab.
The NCI-CTCAE V3.0 toxicity criteria was used to grading the severity of all AEs.
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
1.2%
1/85 • Number of events 1 • Adverse events were collected from the time that the patient received the initial cetuximab infusion and continued during the study until 30 days after the last dose of cetuximab.
The NCI-CTCAE V3.0 toxicity criteria was used to grading the severity of all AEs.
|
|
Psychiatric disorders
Dissociation
|
1.2%
1/85 • Number of events 1 • Adverse events were collected from the time that the patient received the initial cetuximab infusion and continued during the study until 30 days after the last dose of cetuximab.
The NCI-CTCAE V3.0 toxicity criteria was used to grading the severity of all AEs.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
3.5%
3/85 • Number of events 4 • Adverse events were collected from the time that the patient received the initial cetuximab infusion and continued during the study until 30 days after the last dose of cetuximab.
The NCI-CTCAE V3.0 toxicity criteria was used to grading the severity of all AEs.
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
1.2%
1/85 • Number of events 1 • Adverse events were collected from the time that the patient received the initial cetuximab infusion and continued during the study until 30 days after the last dose of cetuximab.
The NCI-CTCAE V3.0 toxicity criteria was used to grading the severity of all AEs.
|
|
Respiratory, thoracic and mediastinal disorders
Lung infiltration
|
1.2%
1/85 • Number of events 1 • Adverse events were collected from the time that the patient received the initial cetuximab infusion and continued during the study until 30 days after the last dose of cetuximab.
The NCI-CTCAE V3.0 toxicity criteria was used to grading the severity of all AEs.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
1.2%
1/85 • Number of events 1 • Adverse events were collected from the time that the patient received the initial cetuximab infusion and continued during the study until 30 days after the last dose of cetuximab.
The NCI-CTCAE V3.0 toxicity criteria was used to grading the severity of all AEs.
|
Other adverse events
| Measure |
Cetuximab
n=85 participants at risk
Initial dose of 400 mg/m2 i.v. over 120 minutes, followed by 250 mg/m2 weekly i.v. over 60 minutes
|
|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
9.4%
8/85 • Number of events 8 • Adverse events were collected from the time that the patient received the initial cetuximab infusion and continued during the study until 30 days after the last dose of cetuximab.
The NCI-CTCAE V3.0 toxicity criteria was used to grading the severity of all AEs.
|
|
Gastrointestinal disorders
Constipation
|
9.4%
8/85 • Number of events 11 • Adverse events were collected from the time that the patient received the initial cetuximab infusion and continued during the study until 30 days after the last dose of cetuximab.
The NCI-CTCAE V3.0 toxicity criteria was used to grading the severity of all AEs.
|
|
Gastrointestinal disorders
Diarrhea
|
14.1%
12/85 • Number of events 17 • Adverse events were collected from the time that the patient received the initial cetuximab infusion and continued during the study until 30 days after the last dose of cetuximab.
The NCI-CTCAE V3.0 toxicity criteria was used to grading the severity of all AEs.
|
|
Gastrointestinal disorders
Nausea
|
15.3%
13/85 • Number of events 14 • Adverse events were collected from the time that the patient received the initial cetuximab infusion and continued during the study until 30 days after the last dose of cetuximab.
The NCI-CTCAE V3.0 toxicity criteria was used to grading the severity of all AEs.
|
|
Gastrointestinal disorders
Stomatitis
|
10.6%
9/85 • Number of events 10 • Adverse events were collected from the time that the patient received the initial cetuximab infusion and continued during the study until 30 days after the last dose of cetuximab.
The NCI-CTCAE V3.0 toxicity criteria was used to grading the severity of all AEs.
|
|
Gastrointestinal disorders
Vomiting
|
9.4%
8/85 • Number of events 11 • Adverse events were collected from the time that the patient received the initial cetuximab infusion and continued during the study until 30 days after the last dose of cetuximab.
The NCI-CTCAE V3.0 toxicity criteria was used to grading the severity of all AEs.
|
|
General disorders
Chills
|
7.1%
6/85 • Number of events 8 • Adverse events were collected from the time that the patient received the initial cetuximab infusion and continued during the study until 30 days after the last dose of cetuximab.
The NCI-CTCAE V3.0 toxicity criteria was used to grading the severity of all AEs.
|
|
General disorders
Fatigue
|
31.8%
27/85 • Number of events 33 • Adverse events were collected from the time that the patient received the initial cetuximab infusion and continued during the study until 30 days after the last dose of cetuximab.
The NCI-CTCAE V3.0 toxicity criteria was used to grading the severity of all AEs.
|
|
General disorders
Oedema peripheral
|
7.1%
6/85 • Number of events 6 • Adverse events were collected from the time that the patient received the initial cetuximab infusion and continued during the study until 30 days after the last dose of cetuximab.
The NCI-CTCAE V3.0 toxicity criteria was used to grading the severity of all AEs.
|
|
General disorders
Pyrexia
|
7.1%
6/85 • Number of events 6 • Adverse events were collected from the time that the patient received the initial cetuximab infusion and continued during the study until 30 days after the last dose of cetuximab.
The NCI-CTCAE V3.0 toxicity criteria was used to grading the severity of all AEs.
|
|
Metabolism and nutrition disorders
Anorexia
|
23.5%
20/85 • Number of events 21 • Adverse events were collected from the time that the patient received the initial cetuximab infusion and continued during the study until 30 days after the last dose of cetuximab.
The NCI-CTCAE V3.0 toxicity criteria was used to grading the severity of all AEs.
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
11.8%
10/85 • Number of events 14 • Adverse events were collected from the time that the patient received the initial cetuximab infusion and continued during the study until 30 days after the last dose of cetuximab.
The NCI-CTCAE V3.0 toxicity criteria was used to grading the severity of all AEs.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
7.1%
6/85 • Number of events 7 • Adverse events were collected from the time that the patient received the initial cetuximab infusion and continued during the study until 30 days after the last dose of cetuximab.
The NCI-CTCAE V3.0 toxicity criteria was used to grading the severity of all AEs.
|
|
Nervous system disorders
Headache
|
29.4%
25/85 • Number of events 28 • Adverse events were collected from the time that the patient received the initial cetuximab infusion and continued during the study until 30 days after the last dose of cetuximab.
The NCI-CTCAE V3.0 toxicity criteria was used to grading the severity of all AEs.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
5.9%
5/85 • Number of events 6 • Adverse events were collected from the time that the patient received the initial cetuximab infusion and continued during the study until 30 days after the last dose of cetuximab.
The NCI-CTCAE V3.0 toxicity criteria was used to grading the severity of all AEs.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
7.1%
6/85 • Number of events 7 • Adverse events were collected from the time that the patient received the initial cetuximab infusion and continued during the study until 30 days after the last dose of cetuximab.
The NCI-CTCAE V3.0 toxicity criteria was used to grading the severity of all AEs.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
5.9%
5/85 • Number of events 6 • Adverse events were collected from the time that the patient received the initial cetuximab infusion and continued during the study until 30 days after the last dose of cetuximab.
The NCI-CTCAE V3.0 toxicity criteria was used to grading the severity of all AEs.
|
|
Skin and subcutaneous tissue disorders
Dermatitis acneiform
|
85.9%
73/85 • Number of events 102 • Adverse events were collected from the time that the patient received the initial cetuximab infusion and continued during the study until 30 days after the last dose of cetuximab.
The NCI-CTCAE V3.0 toxicity criteria was used to grading the severity of all AEs.
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
17.6%
15/85 • Number of events 16 • Adverse events were collected from the time that the patient received the initial cetuximab infusion and continued during the study until 30 days after the last dose of cetuximab.
The NCI-CTCAE V3.0 toxicity criteria was used to grading the severity of all AEs.
|
|
Skin and subcutaneous tissue disorders
Nail disorder
|
10.6%
9/85 • Number of events 12 • Adverse events were collected from the time that the patient received the initial cetuximab infusion and continued during the study until 30 days after the last dose of cetuximab.
The NCI-CTCAE V3.0 toxicity criteria was used to grading the severity of all AEs.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
7.1%
6/85 • Number of events 7 • Adverse events were collected from the time that the patient received the initial cetuximab infusion and continued during the study until 30 days after the last dose of cetuximab.
The NCI-CTCAE V3.0 toxicity criteria was used to grading the severity of all AEs.
|
|
Skin and subcutaneous tissue disorders
Skin disorder
|
7.1%
6/85 • Number of events 7 • Adverse events were collected from the time that the patient received the initial cetuximab infusion and continued during the study until 30 days after the last dose of cetuximab.
The NCI-CTCAE V3.0 toxicity criteria was used to grading the severity of all AEs.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Investigators may not independently publish/disclose any study data, findings or conclusions except as part of an overall multi-center publication. After final publication, or if a draft publication is not produced within approximately 6 months of the final report of the study results, investigators may independently publish, subject to review for sponsor confidential information which may be redacted at sponsor request. Publication may be delayed up to 90 days to seek patent protection.
- Publication restrictions are in place
Restriction type: OTHER