Ewing's Sarcoma Family of Tumors
Conditions
Brief summary
Define the efficacy of CP-751,871 in patients with Ewing's sarcoma family of tumors
Interventions
DRUGCP-751,871
Final dose 30 mg/kg IV on Day 1 of each 28 day cycle until either progression or toxicity
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
10 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Ewing's family of tumors * Current disease state for which there is no curative therapy
Exclusion criteria
* Prior anti-IGF-1R therapy * Concurrent treatment with other anti-cancer agents
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Baseline and every cycle (4 weeks), for up to 6 cycles | Percentage of participants with objective response based on assessment of confirmed complete response (CR) or 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 and no new lesions. PR was defined as ≥30% decrease under baseline of the sum of diameters of all target lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Baseline and every 2 cycles (8 weeks), until death or up to 6 cycles after date of enrollment | Time in months from enrollment to death. For participants who are alive, overall survival was censored at the last contact. |
| Maximum Observed Plasma Concentration (Cmax) | Cycle 1 and Cycle 5: 1 hour post-infusion on Day 1 | — |
| Minimum Observed Plasma Trough Concentration (Cmin) | Cycle 6: predose on Day 1 | Cmin is the concentration at the end of treatment cycle (next cycle predose). |
| Progression-Free Survival (PFS) | Baseline and every cycle (4 weeks), until progression or death | PFS was the time in months from start date to date of first documentation of progression, death due to any cause or symptomatic deterioration (global deterioration of health status requiring discontinuation of treatment). |
| Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) | Cycle 5: 1 hour post-infusion on Day 1 | The dosing interval was 1 cycle (4 weeks) in this study. |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | Cycle 1 and Cycle 5: 1 hour post-infusion on Day 1 | AUClast is the area under the plasma concentration time-curve from zero to the last measured concentration. |
| Number of Participants With Positive Anti-Drug Antibody (ADA) Titer | Cycle 4 (predose on Day 1), 28 days after last dose (End-of-Treatment), and follow-up (approximately 150 days after last dose) | Number of participants with positive sample(s) in the ADA assay and in the neutralizing anti-drug antibodies (NAb) assay. An endpoint titer \<6.64 corresponded to negative ADA category value. |
| Plasma Concentration at End of Infusion (Cendinf) | Cycle 1 Day 2 and Cycle 5 Day 1 | — |
Countries
Australia, Brazil, Canada, Chile, France, Germany, Israel, Italy, Spain, United Kingdom, United States
Participant flow
Recruitment details
Participants were recruited separately for Phase 1 and Phase 2. A total of 138 participants were assigned to received study treatment (31 participants for Phase 1 and 107 participants for Phase 2).
Participants by arm
| Arm | Count |
|---|---|
| Figitumumab Dose Escalation (Phase 1) Figitumumab 20 milligrams per kilogram (mg/kg) intravenous (IV) administered every 4 weeks (1 cycle). If no dose-limiting toxicity (DLT) was identified in the 20-mg/kg cohort, dose escalation proceeded to 30-mg/kg. Oral rapamycin at 2 to 4 mg/day could have been added as salvage therapy. | 10 |
| Figitumumab Dose Extension (Phase 1B) Figitumumab 20 mg/kg or 30 mg/kg IV administered every 4 weeks (1 cycle). Oral rapamycin at 2 to 4 mg/day could have been added as salvage therapy. | 21 |
| Figitumumab 30 mg/kg (Phase 2) Figitumumab 30 mg/kg IV administered every 4 weeks (1 cycle) for up to 12 cycles, unless unacceptable toxicity or participant withdrawal. Oral rapamycin at 2 to 4 mg/day could have been added as salvage therapy. | 107 |
| Total | 138 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Phase 1 | Discontinued | 8 | 0 | 0 |
| Phase 1B | Discontinued | 0 | 19 | 0 |
| Phase 2 | Discontinued | 0 | 0 | 96 |
| Phase 2 | Ongoing at Date of Cut-Off | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Figitumumab Dose Escalation (Phase 1) | Figitumumab Dose Extension (Phase 1B) | Figitumumab 30 mg/kg (Phase 2) | Total |
|---|---|---|---|---|
| Age, Customized 10 to <13 years | 2 participants | 3 participants | 17 participants | 22 participants |
| Age, Customized 13 to <=18 years | 8 participants | 18 participants | 30 participants | 56 participants |
| Age, Customized 18 to <30 years | 0 participants | 0 participants | 43 participants | 43 participants |
| Age, Customized 30 to <41 years | 0 participants | 0 participants | 10 participants | 10 participants |
| Age, Customized >=41 years | 0 participants | 0 participants | 7 participants | 7 participants |
| Sex: Female, Male Female | 4 Participants | 7 Participants | 40 Participants | 51 Participants |
| Sex: Female, Male Male | 6 Participants | 14 Participants | 67 Participants | 87 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 4 | 6 / 6 | 19 / 21 | 1 / 1 | 3 / 4 | 9 / 9 | 99 / 107 | 29 / 29 |
| serious Total, serious adverse events | 2 / 4 | 3 / 6 | 10 / 21 | 0 / 1 | 3 / 4 | 7 / 9 | 47 / 107 | 16 / 29 |
Outcome results
Primary
Objective Response Rate (ORR)
Percentage of participants with objective response based on assessment of confirmed complete response (CR) or 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 and no new lesions. PR was defined as ≥30% decrease under baseline of the sum of diameters of all target lesions.
Time frame: Baseline and every cycle (4 weeks), for up to 6 cycles
Population: All enrolled participants with Ewing's sarcoma family of tumors (ESFT) and who started treatment with figitumumab; number of evaluable participants at data cut-off.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Figitumumab 30 mg/kg (Phase 2) | Objective Response Rate (ORR) | 14.2 percentage of participants |
Secondary
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau)
The dosing interval was 1 cycle (4 weeks) in this study.
Time frame: Cycle 5: 1 hour post-infusion on Day 1
Population: The PK analysis set included all enrolled participants who started treatment and who had sufficient samples to provide interpretable results; number of participants evaluated for measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Figitumumab 30 mg/kg (Phase 2) | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) | 423000 milligram*hour per liter (mg*hr/L) | — |
| Figitumumab 30 mg/kg Dose Escalation (Phase 1) | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) | 475000 milligram*hour per liter (mg*hr/L) | — |
| Figitumumab 30 mg/kg Dose Extension (Phase 1B) | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) | 302900 milligram*hour per liter (mg*hr/L) | Geometric Coefficient of Variation 46 |
Secondary
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
AUClast is the area under the plasma concentration time-curve from zero to the last measured concentration.
Time frame: Cycle 1 and Cycle 5: 1 hour post-infusion on Day 1
Population: The PK analysis set included all enrolled participants who started treatment and who had sufficient samples to provide interpretable results; n=number of participants evaluable for this measure at specified time points for each arm group, respectively.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Figitumumab 30 mg/kg (Phase 2) | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | Cycle 1 (n=3, 5, 16) | 187200 mg*hr/L | Geometric Coefficient of Variation 37 |
| Figitumumab 30 mg/kg (Phase 2) | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | Cycle 5 (n=1, 1, 6) | 423000 mg*hr/L | — |
| Figitumumab 30 mg/kg Dose Escalation (Phase 1) | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | Cycle 1 (n=3, 5, 16) | 338800 mg*hr/L | Geometric Coefficient of Variation 16 |
| Figitumumab 30 mg/kg Dose Escalation (Phase 1) | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | Cycle 5 (n=1, 1, 6) | 509000 mg*hr/L | — |
| Figitumumab 30 mg/kg Dose Extension (Phase 1B) | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | Cycle 1 (n=3, 5, 16) | 343000 mg*hr/L | Geometric Coefficient of Variation 25 |
| Figitumumab 30 mg/kg Dose Extension (Phase 1B) | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | Cycle 5 (n=1, 1, 6) | 310800 mg*hr/L | Geometric Coefficient of Variation 46 |
Secondary
Maximum Observed Plasma Concentration (Cmax)
Time frame: Cycle 1 and Cycle 5: 1 hour post-infusion on Day 1
Population: The pharmacokinetic (PK) analysis set included all enrolled participants who started treatment and who had sufficient samples to provide interpretable results; n=number of participants evaluable for this measure at specified time points for each arm group, respectively.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Figitumumab 30 mg/kg (Phase 2) | Maximum Observed Plasma Concentration (Cmax) | Cycle 1 (n=4, 6, 21) | 513.2 milligrams per liter (mg/L) | Geometric Coefficient of Variation 42 |
| Figitumumab 30 mg/kg (Phase 2) | Maximum Observed Plasma Concentration (Cmax) | Cycle 5 (n=2, 2, 8) | 729.0 milligrams per liter (mg/L) | Geometric Coefficient of Variation 47 |
| Figitumumab 30 mg/kg Dose Escalation (Phase 1) | Maximum Observed Plasma Concentration (Cmax) | Cycle 5 (n=2, 2, 8) | 1133 milligrams per liter (mg/L) | Geometric Coefficient of Variation 9 |
| Figitumumab 30 mg/kg Dose Escalation (Phase 1) | Maximum Observed Plasma Concentration (Cmax) | Cycle 1 (n=4, 6, 21) | 1075 milligrams per liter (mg/L) | Geometric Coefficient of Variation 21 |
| Figitumumab 30 mg/kg Dose Extension (Phase 1B) | Maximum Observed Plasma Concentration (Cmax) | Cycle 1 (n=4, 6, 21) | 975.6 milligrams per liter (mg/L) | Geometric Coefficient of Variation 26 |
| Figitumumab 30 mg/kg Dose Extension (Phase 1B) | Maximum Observed Plasma Concentration (Cmax) | Cycle 5 (n=2, 2, 8) | 1043 milligrams per liter (mg/L) | Geometric Coefficient of Variation 47 |
Secondary
Minimum Observed Plasma Trough Concentration (Cmin)
Cmin is the concentration at the end of treatment cycle (next cycle predose).
Time frame: Cycle 6: predose on Day 1
Population: The PK analysis set included all enrolled participants who started treatment and who had sufficient samples to provide interpretable results; number of participants evaluated for measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Figitumumab 30 mg/kg (Phase 2) | Minimum Observed Plasma Trough Concentration (Cmin) | 389.0 mg/L | — |
| Figitumumab 30 mg/kg Dose Escalation (Phase 1) | Minimum Observed Plasma Trough Concentration (Cmin) | 345.0 mg/L | — |
| Figitumumab 30 mg/kg Dose Extension (Phase 1B) | Minimum Observed Plasma Trough Concentration (Cmin) | 283.6 mg/L | Geometric Coefficient of Variation 53 |
Secondary
Number of Participants With Positive Anti-Drug Antibody (ADA) Titer
Number of participants with positive sample(s) in the ADA assay and in the neutralizing anti-drug antibodies (NAb) assay. An endpoint titer \<6.64 corresponded to negative ADA category value.
Time frame: Cycle 4 (predose on Day 1), 28 days after last dose (End-of-Treatment), and follow-up (approximately 150 days after last dose)
Population: All enrolled participants with ESFT and who started treatment with figitumumab. None of the serum samples were positive for ADAs following repeated administration of figitumumab, as indicated by an endpoint titer of \<6.64.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Figitumumab 30 mg/kg (Phase 2) | Number of Participants With Positive Anti-Drug Antibody (ADA) Titer | 0 participants |
Secondary
Overall Survival (OS)
Time in months from enrollment to death. For participants who are alive, overall survival was censored at the last contact.
Time frame: Baseline and every 2 cycles (8 weeks), until death or up to 6 cycles after date of enrollment
Population: All enrolled participants with ESFT and who started treatment with figitumumab.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Figitumumab 30 mg/kg (Phase 2) | Overall Survival (OS) | 8.9 months |
Secondary
Plasma Concentration at End of Infusion (Cendinf)
Time frame: Cycle 1 Day 2 and Cycle 5 Day 1
Population: The PK analysis set included all enrolled participants who started treatment and who had sufficient samples to provide interpretable results; n=number of participants evaluable for this measure at specified time points for each arm group, respectively.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Figitumumab 30 mg/kg (Phase 2) | Plasma Concentration at End of Infusion (Cendinf) | Cycle 1 (n=4, 6, 21) | 513.2 mg/L | Geometric Coefficient of Variation 42 |
| Figitumumab 30 mg/kg (Phase 2) | Plasma Concentration at End of Infusion (Cendinf) | Cycle 5 (n=2, 2, 8) | 729.0 mg/L | Geometric Coefficient of Variation 47 |
| Figitumumab 30 mg/kg Dose Escalation (Phase 1) | Plasma Concentration at End of Infusion (Cendinf) | Cycle 1 (n=4, 6, 21) | 1075 mg/L | Geometric Coefficient of Variation 21 |
| Figitumumab 30 mg/kg Dose Escalation (Phase 1) | Plasma Concentration at End of Infusion (Cendinf) | Cycle 5 (n=2, 2, 8) | 1133 mg/L | Geometric Coefficient of Variation 9 |
| Figitumumab 30 mg/kg Dose Extension (Phase 1B) | Plasma Concentration at End of Infusion (Cendinf) | Cycle 1 (n=4, 6, 21) | 975.6 mg/L | Geometric Coefficient of Variation 26 |
| Figitumumab 30 mg/kg Dose Extension (Phase 1B) | Plasma Concentration at End of Infusion (Cendinf) | Cycle 5 (n=2, 2, 8) | 1043 mg/L | Geometric Coefficient of Variation 47 |
Secondary
Progression-Free Survival (PFS)
PFS was the time in months from start date to date of first documentation of progression, death due to any cause or symptomatic deterioration (global deterioration of health status requiring discontinuation of treatment).
Time frame: Baseline and every cycle (4 weeks), until progression or death
Population: All enrolled participants with ESFT and who started treatment with figitumumab.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Figitumumab 30 mg/kg (Phase 2) | Progression-Free Survival (PFS) | 1.9 months |