Colorectal Neoplasm
Conditions
Keywords
Refractory Colorectal, Single arm, Phase 2
Brief summary
This study will test if there is any survival benefit in patients with refractory metastatic colorectal cancer that receive CP-751, 871.
Interventions
BIOLOGICALCP-751, 871
Human IgG2 Monoclonal Antibody. 20mg/kg or 30 mg/kg every 3 weeks for 17 cycles, until progression or unacceptable toxicity develops.
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients who have stage IV colorectal cancer * Patients whose disease has worsened despite prior anti-cancer therapy * Patients who have satisfactory bonemarrow, kidney and liver function
Exclusion criteria
* Patients who are being simultaneously treated with another anti-cancer therapy. * Patients who have previously received anti-cancer therapy that works like CP-751, 871 (targets insulin-like growth factor receptor) * Patients that are pregnant or breast-feeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Estimate of the 6 Month Survival Probability | Baseline up to Month 6 | The 6 month survival probability was defined as the probability of survival at 6 months based on the Kaplan-Meier estimate. The time was from date of enrollment to date of death due to any cause. For participants who were last known to be alive, overall survival was censored at the last contact date. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | Baseline until tumor progression or censorship, up to 33 months. The frequency of tumor assessments was screening, every cycle, end of treatment (within 28 days of last dose of study drug), and follow-up. | The period from study entry until disease progression. Participants without progression or death were censored at time of last disease assessment. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as 20% increase in the sum of longest diameters of target measurable lesions, or a clear increase in a non-target lesion, or the apprearance of new lesions. |
| Percentage of Participants With Objective Response | Baseline, every cycle (Day 15-21 or according to local standard), end of treatment (within 28 days of last dose of study drug) and follow-up (150 days after last dose of study drug), up to 33 months | Percentage of participants with OR based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). CR was defined as complete disappearance of all target and non-target disease. PR applied only to participants with at least one measurable lesion. Greater than or equal to 30 % decrease under baseline of the sum of longest diameters of all target measurable lesions. |
| Descriptive Summary of Figitumumab Concentration Versus Time | Pre-dose on Day 1, 1 hour after end of infusion (post-dose) on Day 2 in Cycle 1, pre-dose on Day 1 in Cycles 2,3,4, 1 hour post-dose on Day 1 in Cycle 5 | The measurement of mean plasma concentration of figitumumab in Day 1 of Cycle 1,2,3,4,5 |
| Overall Survival | From date of enrollment until death or censorship, up to 33 months | The time from date of enrollment to date of death due to any cause. For participants who were last known to be alive, overall survival was censored at the last contact date. |
| Counts of Circulating Tumor Cells (CTCs) Expressing Positive Insulin-like Growth Factor 1 Receptor (IGF-1R) | Cycle 1 pre-dosing and Cycle 4 pre-dosing | The quantification of circulating tumor cells (CTCs) expressing the IGF-1R in this patient population. Blood samples were collected, and were measured using an automated microscope system. |
| Counts of Circulating Tumor Cells (CTCs) | Cycle 1 pre-dosing and Cycle 4 pre-dosing | The quantification of circulating tumor cells (CTCs)in this patient population. Blood samples were collected, and were measured using an automated microscope system. |
| Participants Reporting Positive for Total Anti-drug Antibodies (ADA) | Up to 2 hours prior to infusion in Cycles 1 and 4, at the end of treatment, and at the 4th scheduled follow-up visit (~150 days after the last infusion) | The immunogenicity of figitumumab in terms of producing an antidrug antibody (ADA) response were monitored. |
Countries
Spain, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Figitumumab 20 mg/kg Figitumumab (CP-751,871) was given in 3-week cycles for a total of up to 17 cycles. Participants can receive treatment beyond 17 cycles provided clinical benefit is being achieved. Figitumumab 20 milligram/kilogram (mg/kg) was administered as an intravenous (IV) infusion on Day 1 and 2 in Cycle 1 (loading dose), and on Day 1 of every cycle thereafter. | 85 |
| Figitumumab 30 mg/kg Figitumumab (CP-751,871) was given in 3-week cycles for a total of up to 17 cycles. Participants can receive treatment beyond 17 cycles provided clinical benefit is being achieved. Figitumumab 30 milligram/kilogram (mg/kg) was administered as an IV infusion on Day 1 and 2 in Cycle 1 (loading dose), and on Day 1 of every cycle thereafter. | 83 |
| Total | 168 |
Baseline characteristics
| Characteristic | Figitumumab 20 mg/kg | Figitumumab 30 mg/kg | Total |
|---|---|---|---|
| Age, Customized <65 years | 56 participants | 59 participants | 115 participants |
| Age, Customized >=65 years | 29 participants | 24 participants | 53 participants |
| Sex: Female, Male Female | 39 Participants | 35 Participants | 74 Participants |
| Sex: Female, Male Male | 46 Participants | 48 Participants | 94 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 85 / 85 | 83 / 83 |
| serious Total, serious adverse events | 56 / 85 | 53 / 83 |
Outcome results
Primary
Estimate of the 6 Month Survival Probability
The 6 month survival probability was defined as the probability of survival at 6 months based on the Kaplan-Meier estimate. The time was from date of enrollment to date of death due to any cause. For participants who were last known to be alive, overall survival was censored at the last contact date.
Time frame: Baseline up to Month 6
Population: All enrolled participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Figitumumab 20 mg/kg | Estimate of the 6 Month Survival Probability | 49.4 Percent chance of survival |
| Figitumumab 30 mg/kg | Estimate of the 6 Month Survival Probability | 44.1 Percent chance of survival |
Comparison: The hypotheses for each group were H0:p=0.45 vs H1:p\>0.45. There was one interim analysis for futility for each group based on the method of Case and Morgan. The futility boundary was not crossed for 20/kg mg group, but was crossed for the 30/kg mg group. It was recommended to investigators that participants be discontinued from treatment with 30 mg/kg of figitumumab.p-value: >0.05Test of probability of 6 month survival
Secondary
Counts of Circulating Tumor Cells (CTCs)
The quantification of circulating tumor cells (CTCs)in this patient population. Blood samples were collected, and were measured using an automated microscope system.
Time frame: Cycle 1 pre-dosing and Cycle 4 pre-dosing
Population: All enrolled participants who started treatment and who have at least one sample submitted. The total number of participants for this outcome measure was less than the original population. N means the numbers of units analyzed in Pre-treatment and/or Baseline, and Post-Baseline and/or Follow-up, respectively.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Figitumumab 20 mg/kg | Counts of Circulating Tumor Cells (CTCs) | Pre-treatment and/or baseline (n=44,71) | 7.25 Number of CTC/ml of blood | Standard Deviation 16.59 |
| Figitumumab 20 mg/kg | Counts of Circulating Tumor Cells (CTCs) | Post-Baseline and/or follow-up (n=19,17) | 1.26 Number of CTC/ml of blood | Standard Deviation 1.94 |
| Figitumumab 30 mg/kg | Counts of Circulating Tumor Cells (CTCs) | Pre-treatment and/or baseline (n=44,71) | 4.90 Number of CTC/ml of blood | Standard Deviation 9.83 |
| Figitumumab 30 mg/kg | Counts of Circulating Tumor Cells (CTCs) | Post-Baseline and/or follow-up (n=19,17) | 2.18 Number of CTC/ml of blood | Standard Deviation 7.06 |
Secondary
Counts of Circulating Tumor Cells (CTCs) Expressing Positive Insulin-like Growth Factor 1 Receptor (IGF-1R)
The quantification of circulating tumor cells (CTCs) expressing the IGF-1R in this patient population. Blood samples were collected, and were measured using an automated microscope system.
Time frame: Cycle 1 pre-dosing and Cycle 4 pre-dosing
Population: All enrolled participants who started treatment and who have at least one sample submitted. The total number of participants for this outcome measure was less than the original population. N means the numbers of units analyzed in Pre-treatment and/or Baseline, and Post-Baseline and/or Follow-up, respectively.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Figitumumab 20 mg/kg | Counts of Circulating Tumor Cells (CTCs) Expressing Positive Insulin-like Growth Factor 1 Receptor (IGF-1R) | Pre-treatment and/or baseline (n=44,71) | 2.02 number of CTC expressing IGF-1R/ml blood | Standard Deviation 8.79 |
| Figitumumab 20 mg/kg | Counts of Circulating Tumor Cells (CTCs) Expressing Positive Insulin-like Growth Factor 1 Receptor (IGF-1R) | Post-Baseline and/or follow-up (n=18,17) | 0.22 number of CTC expressing IGF-1R/ml blood | Standard Deviation 0.55 |
| Figitumumab 30 mg/kg | Counts of Circulating Tumor Cells (CTCs) Expressing Positive Insulin-like Growth Factor 1 Receptor (IGF-1R) | Pre-treatment and/or baseline (n=44,71) | 0.54 number of CTC expressing IGF-1R/ml blood | Standard Deviation 1.29 |
| Figitumumab 30 mg/kg | Counts of Circulating Tumor Cells (CTCs) Expressing Positive Insulin-like Growth Factor 1 Receptor (IGF-1R) | Post-Baseline and/or follow-up (n=18,17) | 0.00 number of CTC expressing IGF-1R/ml blood | Standard Deviation 0 |
Secondary
Descriptive Summary of Figitumumab Concentration Versus Time
The measurement of mean plasma concentration of figitumumab in Day 1 of Cycle 1,2,3,4,5
Time frame: Pre-dose on Day 1, 1 hour after end of infusion (post-dose) on Day 2 in Cycle 1, pre-dose on Day 1 in Cycles 2,3,4, 1 hour post-dose on Day 1 in Cycle 5
Population: All participants for whom PK was assessed at least once. The numbers of participants analyzed are numbers of observation (non-missing concentrations). The numbers for 20 mg/kg group are 84,7,3,2,13 for five cycles, respectively. The numbers for 30 mg/kg group are 79,8,2,2,8 for five cycles, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Figitumumab 20 mg/kg | Descriptive Summary of Figitumumab Concentration Versus Time | Cycle2/Day1 | 244.0 miligrams/liter (mg/L) | Standard Deviation 114 |
| Figitumumab 20 mg/kg | Descriptive Summary of Figitumumab Concentration Versus Time | Cycle4/Day1 | 76.30 miligrams/liter (mg/L) | Standard Deviation 1.2728 |
| Figitumumab 20 mg/kg | Descriptive Summary of Figitumumab Concentration Versus Time | Cycle3/Day1 | 255.7 miligrams/liter (mg/L) | Standard Deviation 60.476 |
| Figitumumab 20 mg/kg | Descriptive Summary of Figitumumab Concentration Versus Time | CYcle5/Day1 | 756.2 miligrams/liter (mg/L) | Standard Deviation 239.08 |
| Figitumumab 20 mg/kg | Descriptive Summary of Figitumumab Concentration Versus Time | Cycle1/Day2 | 647.0 miligrams/liter (mg/L) | Standard Deviation 288.23 |
| Figitumumab 30 mg/kg | Descriptive Summary of Figitumumab Concentration Versus Time | CYcle5/Day1 | 745.5 miligrams/liter (mg/L) | Standard Deviation 216.14 |
| Figitumumab 30 mg/kg | Descriptive Summary of Figitumumab Concentration Versus Time | Cycle1/Day2 | 877.7 miligrams/liter (mg/L) | Standard Deviation 230.22 |
| Figitumumab 30 mg/kg | Descriptive Summary of Figitumumab Concentration Versus Time | Cycle2/Day1 | 221.0 miligrams/liter (mg/L) | Standard Deviation 119.65 |
| Figitumumab 30 mg/kg | Descriptive Summary of Figitumumab Concentration Versus Time | Cycle3/Day1 | 245.0 miligrams/liter (mg/L) | Standard Deviation 19.799 |
| Figitumumab 30 mg/kg | Descriptive Summary of Figitumumab Concentration Versus Time | Cycle4/Day1 | 427.0 miligrams/liter (mg/L) | Standard Deviation 86.267 |
Secondary
Overall Survival
The time from date of enrollment to date of death due to any cause. For participants who were last known to be alive, overall survival was censored at the last contact date.
Time frame: From date of enrollment until death or censorship, up to 33 months
Population: All enrolled participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Figitumumab 20 mg/kg | Overall Survival | 5.8 Months |
| Figitumumab 30 mg/kg | Overall Survival | 5.6 Months |
Secondary
Participants Reporting Positive for Total Anti-drug Antibodies (ADA)
The immunogenicity of figitumumab in terms of producing an antidrug antibody (ADA) response were monitored.
Time frame: Up to 2 hours prior to infusion in Cycles 1 and 4, at the end of treatment, and at the 4th scheduled follow-up visit (~150 days after the last infusion)
Population: Participants for whom at least one ADA measurement was done. The outcome was not analyzed and only listing of ADA level for each participant was available.
Secondary
Percentage of Participants With Objective Response
Percentage of participants with OR based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). CR was defined as complete disappearance of all target and non-target disease. PR applied only to participants with at least one measurable lesion. Greater than or equal to 30 % decrease under baseline of the sum of longest diameters of all target measurable lesions.
Time frame: Baseline, every cycle (Day 15-21 or according to local standard), end of treatment (within 28 days of last dose of study drug) and follow-up (150 days after last dose of study drug), up to 33 months
Population: Per protocol. All enrolled participants who started treatment, with measurable disease and adequate baseline assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Figitumumab 20 mg/kg | Percentage of Participants With Objective Response | 0 Percentage of participants |
| Figitumumab 30 mg/kg | Percentage of Participants With Objective Response | 0 Percentage of participants |
Secondary
Progression-Free Survival (PFS)
The period from study entry until disease progression. Participants without progression or death were censored at time of last disease assessment. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as 20% increase in the sum of longest diameters of target measurable lesions, or a clear increase in a non-target lesion, or the apprearance of new lesions.
Time frame: Baseline until tumor progression or censorship, up to 33 months. The frequency of tumor assessments was screening, every cycle, end of treatment (within 28 days of last dose of study drug), and follow-up.
Population: All enrolled participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Figitumumab 20 mg/kg | Progression-Free Survival (PFS) | 1.4 months |
| Figitumumab 30 mg/kg | Progression-Free Survival (PFS) | 1.4 months |