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| ID | Type | Description | Link |
|---|---|---|---|
| MK-7454-006 | Other Identifier | Merck Protocol Number |
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Study was terminated for business reasons.
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This is a Phase 1/1B, non-randomized, open-label, dose-escalation study of robatumumab (SCH 717454, MK-7454) administered in combination with chemotherapy in pediatric participants with solid tumors, to be conducted in conformance with Good Clinical Practices. This study will evaluate the safety, tolerability and dose-finding of robatumumab when administered in combination with temozolomide and irinotecan (Arm A); or cyclophosphamide, doxorubicin, and vincristine (Arm B), or ifosfamide and etoposide (Arm C).
The primary study hypothesis is that robatumumab can be safely administered in combination with chemotherapy regimens in pediatric participants with solid tumors.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Temozolomide+Irinotecan+Robatumumab | Experimental | Participants receive temozolomide 100 mg/m^2/day intravenously (IV) on Days 1-5 PLUS irinotecan 10 mg/m^2/day IV on Days 1-5 and Days 8-12 PLUS robatumumab 10 mg/kg or 20 mg/kg IV on Day 1 of each 3-week cycle. |
|
| Vincristine+Doxorubicin+Cyclophosphamide+Robatumumab | Experimental | Participants receive vincristine 2 mg/m^2 (maximum 2 mg) IV on Day 1 PLUS cyclophosphamide 1200 mg/m^2 IV on Day 1 PLUS doxorubicin hydrochloride 75 mg/m^2 IV continuously over 48 hours PLUS robatumumab 10 mg/kg or 20 mg/kg IV on Day 1 of each 3-week cycle. |
|
| Ifosfamide+Etoposide+Robatumumab | Experimental | Participants receive ifosfamide 1800 mg/m^2 per day IV PLUS etoposide 100 mg/m^2 per day IV on Days 1-5 PLUS robatumumab 10 mg/kg or 20 mg/kg IV on Day 1 of each 3-week cycle. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Temozolomide | Drug |
| ||
| Vincristine |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Dose Limiting Toxicities | Dose-limiting toxicity was defined by the following adverse events (AEs) that were considered possibly or probably related to either robatumumab or to its interaction with the chemotherapy regimen assigned: neutropenia (Grade 4 for >1 week that did not resolve prior to Day 1 of the next cycle; Grade 3-4 neutropenia with Grade ≥2 fever lasting 3 days; neutropenic infection; failure to recover to study entry/eligibility criteria laboratory requirement levels that resulted in a delay of 14 days between treatment cycles), thrombocytopenia (Grade 4 for >1 week that did not resolve prior to Day 1 of the next cycle; Grade 3-4 requiring a platelet transfusion on 2 separate days within a cycle) or all other AEs (Grade ≥3 [any duration] not ameliorable by supportive or symptomatic measures). The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE version 4.0) was to be used to grade AEs. | Up to ~30 days after last dose of study drug (Up to ~10.3 months) |
| Measure | Description | Time Frame |
|---|---|---|
| Best Overall Response Based on Response Evaluation Criteria in Solid Tumors (RECIST) | All measurable lesions up to a maximum of 5 lesions per organ and 10 lesions in total, representative of all involved organs were to be identified as target lesions. Data were to be collected at Screening, every 6 weeks and at 30 days after the final dose of robatumumab or the standard treatment assigned (whichever was last). The best overall response was to be the best response recorded from the start of the treatment until disease progression/recurrence. Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): >30% decrease in the sum of the longest diameter (LD) of target lesions; Progressive Disease (PD): >20% increase in the sum of the LD of target lesions or the appearance of one or more new lesions; or Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
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| ID | Type | URL | Comment |
|---|---|---|---|
| CSR Synopsis | View IPD |
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| ID | Title | Description |
|---|---|---|
| FG000 | Temozolomide+Irinotecan+Robatumumab | Participants receive temozolomide 100 mg/m^2/day intravenously (IV) on Days 1-5 PLUS irinotecan 10 mg/m^2/day IV on Days 1-5 and Days 8-12 PLUS robatumumab 10 mg/kg or 20 mg/kg IV on Day 1 of each 3-week cycle. |
| FG001 | Vincristine+Doxorubicin+Cyclophosphamide+Robatumumab |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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|
| Ifosfamide | Drug |
|
| Irinotecan | Drug |
|
| Robatumumab | Biological |
|
| Doxorubicin | Drug |
|
| Cyclophosphamide | Drug |
|
| Etoposide | Drug |
|
| Screening, every 6 weeks and at ~30 days after last dose of study drug (Up to ~10.3 months) |
| Maximum Observed Concentration (Cmax) of Robatumumab | Cmax was defined as the maximum observed serum concentration of robatumumab when administered in combination with other treatments. Blood samples for analysis of robatumumab pharmacokinetics (PK) were to be obtained at Cycles 1 and 2 at the following time points: predose, immediately post-infusion, and at 3, 6, 24, 48, 168, 336, and 504 hours post the start time of infusion. For all odd-numbered cycles (Cycle 3 and on) samples were to be obtained at each of the following two time points: predose and immediately postdose of robatumumab. Additionally, PK samples were to be obtained at the Post Study Visits 1 (30 days after last dose of robatumumab or standard treatment and 2 (approximately 4 months after last dose of robatumumab or standard treatment). | Cycles 1 & 2: pre- and post-infusion, and at 3, 6, 24, 48, 168, 336, and 504 hours post start of infusion; then pre-and post-dose in odd-numbered cycles, and Post Study Visits 1 and 2 |
| Plasma Level of Insulin-like Growth Factor-I (IGF-I) | IGF-I is produced largely by the liver in response to growth hormone from the hypothalamic-pituitary axis. The IGF ligands can promote neoplastic events (cancer growth) through a number of different mechanisms. Robatumumab inhibits IGF ligand binding, IGF-stimulated receptor phosphorylation and human tumor cell proliferation. Plasma levels of IGF-I were to be analyzed on Day 1 of Cycles 1, 2, 3, 5, and approximately 30 days after the final dose of robatumumab or the standard treatment assigned (whichever was last). | On Day 1 of Cycles 1, 2, 3 and 5, and ~30 days after last dose of study drug (Up to~10.3 months) |
| Number of Participants Who Developed Anti-robatumumab Antibodies | The incidence of anti-robatumumab antibodies was to be assessed. Only participants who had a negative pre-treatment sample and a post-treatment sample were considered to be evaluable. If a participant had a single sample considered positive in the anti-robatumumab antibody assay (with the exception of pre-treatment positive participants), then they would be counted as positive in the immunogenicity assessment. | Prior to 1st and 8th doses of robatumumab, ~30 days after last dose of study drug, and 4 months after last dose of study drug (Up to ~13.3 months) |
| Time to Maximum Observed Concentration (Tmax) of Robatumumab | Tmax was defined as time of Cmax of robatumumab when administered in combination with other treatments. Blood samples for analysis of robatumumab PK were to be obtained at Cycles 1 and 2 at the following time points: predose, immediately post-infusion, and at 3, 6, 24, 48, 168, 336, and 504 hours post the start time of infusion. For all odd-numbered cycles (Cycle 3 and on) samples were to be obtained at each of the following two time points: predose and immediately postdose of robatumumab. Additionally, PK samples were to be obtained at the Post Study Visits 1 (30 days after last dose of robatumumab or standard treatment and 2 (approximately 4 months after last dose of robatumumab or standard treatment). | Cycles 1 & 2: pre- and post-infusion, and at 3, 6, 24, 48, 168, 336, and 504 hours post start of infusion; then pre-and post-dose in odd-numbered cycles, and Post Study Visits 1 and 2 |
| Area Under the Curve at the Time of Final Quantifiable Sample (AUCtf) for Robatumumab | AUCtf for robatumumab was defined as the area under the curve at the time of the final quantifiable sample of robatumumab. Blood samples for analysis of robatumumab PK were to be obtained at Cycles 1 and 2 at the following time points: predose, immediately post-infusion, and at 3, 6, 24, 48, 168, 336, and 504 hours post the start time of infusion. For all odd-numbered cycles (Cycle 3 and on) samples were to be obtained at each of the following two time points: predose and immediately postdose of robatumumab. Additionally, PK samples were to be obtained at the Post Study Visits 1 (30 days after last dose of robatumumab or standard treatment and 2 (approximately 4 months after last dose of robatumumab or standard treatment). | Cycles 1 & 2: pre- and post-infusion, and at 3, 6, 24, 48, 168, 336, and 504 hours post start of infusion; then pre-and post-dose in odd-numbered cycles, and Post Study Visits 1 and 2 |
| Area Under the Curve During a Dosing Interval Ï„ (AUCÏ„) for Robatumumab | AUCÏ„ was defined as the area under the plasma concentration-time curve during a dosage interval (Ï„). Blood samples for analysis of robatumumab PK were to be obtained at Cycles 1 and 2 at the following time points: predose, immediately post-infusion, and at 3, 6, 24, 48, 168, 336, and 504 hours post the start time of infusion. For all odd-numbered cycles (Cycle 3 and on) samples were to be obtained at each of the following two time points: predose and immediately postdose of robatumumab. Additionally, PK samples were to be obtained at the Post Study Visits 1 (30 days after last dose of robatumumab or standard treatment and 2 (approximately 4 months after last dose of robatumumab or standard treatment). | Cycles 1 & 2: pre- and post-infusion, and at 3, 6, 24, 48, 168, 336, and 504 hours post start of infusion; then pre-and post-dose in odd-numbered cycles, and Post Study Visits 1 and 2 |
| Plasma Level of Insulin-like Growth Factor-2 (IGF-II) | IGF-II is generally produced locally in response to growth hormone from the hypothalamic-pituitary axis. The IGF ligands can promote neoplastic events (cancer growth) through a number of different mechanisms. Robatumumab inhibits IGF ligand binding, IGF-stimulated receptor phosphorylation and human tumor cell proliferation. Plasma levels of IGF-II were to be analyzed on Day 1 of Cycles 1, 2, 3, 5, and approximately 30 days after the final dose of robatumumab or the standard treatment assigned (whichever was last). | On Day 1 of Cycles 1, 2, 3 and 5, and ~30 days after last dose of study drug (Up to~10.3 months) |
| Plasma Level of Insulin-like Growth Factor Binding Protein-2 (IGFBP-2) | The IGFBP-2 protein is secreted into the bloodstream where it binds to IGF-I and IGF-II. High expression levels of this protein promote the growth of several types of tumors and may be predictive of the chances of recovery of the participant. Robatumumab inhibits expression of this protein. Plasma levels of IGFBP-2 were to be analyzed on Day 1 of Cycles 1, 2, 3, 5, and approximately 30 days after the final dose of robatumumab or the standard treatment assigned (whichever was last). | On Day 1 of Cycles 1, 2, 3 and 5, and ~30 days after last dose of study drug (Up to~10.3 months) |
| Plasma Level of Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) | The IGFBP-3 protein is secreted into the bloodstream where it binds to IGF-I and IGF-II. High expression levels of this protein promote the growth of several types of tumors and may be predictive of the chances of recovery of the participant. Robatumumab inhibits expression of this protein. Plasma levels of IGFBP-3 were to be analyzed on Day 1 of Cycles 1, 2, 3, 5, and approximately 30 days after the final dose of robatumumab or the standard treatment assigned (whichever was last). | On Day 1 of Cycles 1, 2, 3 and 5, and ~30 days after last dose of study drug (Up to~10.3 months) |
Participants receive vincristine 2 mg/m^2 (maximum 2 mg) IV on Day 1 PLUS cyclophosphamide 1200 mg/m^2 IV on Day 1 PLUS doxorubicin hydrochloride 75 mg/m^2 IV continuously over 48 hours PLUS robatumumab 10 mg/kg or 20 mg/kg IV on Day 1 of each 3-week cycle. |
| FG002 | Ifosfamide+Etoposide+Robatumumab | Participants receive ifosfamide 1800 mg/m^2 per day IV PLUS etoposide 100 mg/m^2 per day IV on Days 1-5 PLUS robatumumab 10 mg/kg or 20 mg/kg IV on Day 1 of each 3-week cycle. |
| COMPLETED |
|
| NOT COMPLETED |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Temozolomide+Irinotecan+Robatumumab | Participants receive temozolomide 100 mg/m^2/day IV on Days 1-5 PLUS irinotecan 10 mg/m^2/day IV on Days 1-5 and Days 8-12 PLUS robatumumab 10 mg/kg or 20 mg/kg IV on Day 1 of each 3-week cycle. |
| BG001 | Vincristine+Doxorubicin+Cyclophosphamide+Robatumumab | Participants receive vincristine 2 mg/m^2 (maximum 2 mg) IV on Day 1 PLUS cyclophosphamide 1200 mg/m^2 IV on Day 1 PLUS doxorubicin hydrochloride 75 mg/m^2 IV continuously over 48 hours PLUS robatumumab 10 mg/kg or 20 mg/kg IV on Day 1 of each 3-week cycle. |
| BG002 | Ifosfamide+Etoposide+Robatumumab | Participants receive ifosfamide 1800 mg/m^2 per day IV PLUS etoposide 100 mg/m^2 per day IV on Days 1-5 PLUS robatumumab 10 mg/kg or 20 mg/kg IV on Day 1 of each 3-week cycle. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Dose Limiting Toxicities | Dose-limiting toxicity was defined by the following adverse events (AEs) that were considered possibly or probably related to either robatumumab or to its interaction with the chemotherapy regimen assigned: neutropenia (Grade 4 for >1 week that did not resolve prior to Day 1 of the next cycle; Grade 3-4 neutropenia with Grade ≥2 fever lasting 3 days; neutropenic infection; failure to recover to study entry/eligibility criteria laboratory requirement levels that resulted in a delay of 14 days between treatment cycles), thrombocytopenia (Grade 4 for >1 week that did not resolve prior to Day 1 of the next cycle; Grade 3-4 requiring a platelet transfusion on 2 separate days within a cycle) or all other AEs (Grade ≥3 [any duration] not ameliorable by supportive or symptomatic measures). The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE version 4.0) was to be used to grade AEs. | All Treated Set was defined as all participants who received ≥1 dose of robatumumab or chemotherapy. | Posted | Number | Participants | Up to ~30 days after last dose of study drug (Up to ~10.3 months) |
|
|
| ||||||||||||||||||||||||||||||||
| Secondary | Best Overall Response Based on Response Evaluation Criteria in Solid Tumors (RECIST) | All measurable lesions up to a maximum of 5 lesions per organ and 10 lesions in total, representative of all involved organs were to be identified as target lesions. Data were to be collected at Screening, every 6 weeks and at 30 days after the final dose of robatumumab or the standard treatment assigned (whichever was last). The best overall response was to be the best response recorded from the start of the treatment until disease progression/recurrence. Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): >30% decrease in the sum of the longest diameter (LD) of target lesions; Progressive Disease (PD): >20% increase in the sum of the LD of target lesions or the appearance of one or more new lesions; or Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. | All Treated Set was defined as all participants who received ≥1 dose of robatumumab or chemotherapy. | Posted | Number | Participants | Screening, every 6 weeks and at ~30 days after last dose of study drug (Up to ~10.3 months) |
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| Secondary | Maximum Observed Concentration (Cmax) of Robatumumab | Cmax was defined as the maximum observed serum concentration of robatumumab when administered in combination with other treatments. Blood samples for analysis of robatumumab pharmacokinetics (PK) were to be obtained at Cycles 1 and 2 at the following time points: predose, immediately post-infusion, and at 3, 6, 24, 48, 168, 336, and 504 hours post the start time of infusion. For all odd-numbered cycles (Cycle 3 and on) samples were to be obtained at each of the following two time points: predose and immediately postdose of robatumumab. Additionally, PK samples were to be obtained at the Post Study Visits 1 (30 days after last dose of robatumumab or standard treatment and 2 (approximately 4 months after last dose of robatumumab or standard treatment). | All Treated Set was defined as all participants who received ≥1 dose of robatumumab or chemotherapy. Individual data were collected, but, due to study termination and small numbers of participants, summary data for Cmax were not produced. | Posted | Cycles 1 & 2: pre- and post-infusion, and at 3, 6, 24, 48, 168, 336, and 504 hours post start of infusion; then pre-and post-dose in odd-numbered cycles, and Post Study Visits 1 and 2 |
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| Secondary | Plasma Level of Insulin-like Growth Factor-I (IGF-I) | IGF-I is produced largely by the liver in response to growth hormone from the hypothalamic-pituitary axis. The IGF ligands can promote neoplastic events (cancer growth) through a number of different mechanisms. Robatumumab inhibits IGF ligand binding, IGF-stimulated receptor phosphorylation and human tumor cell proliferation. Plasma levels of IGF-I were to be analyzed on Day 1 of Cycles 1, 2, 3, 5, and approximately 30 days after the final dose of robatumumab or the standard treatment assigned (whichever was last). | All Treated Set was defined as all participants who received ≥1 dose of robatumumab or chemotherapy. Individual data were collected, but, due to study termination and small numbers of participants, summary data for IGF-I were not produced. | Posted | On Day 1 of Cycles 1, 2, 3 and 5, and ~30 days after last dose of study drug (Up to~10.3 months) |
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| Secondary | Number of Participants Who Developed Anti-robatumumab Antibodies | The incidence of anti-robatumumab antibodies was to be assessed. Only participants who had a negative pre-treatment sample and a post-treatment sample were considered to be evaluable. If a participant had a single sample considered positive in the anti-robatumumab antibody assay (with the exception of pre-treatment positive participants), then they would be counted as positive in the immunogenicity assessment. | All Treated Set was defined as all participants who received ≥1 dose of robatumumab or chemotherapy and had a negative pre-treatment sample and a post-treatment sample. | Posted | Number | Participants | Prior to 1st and 8th doses of robatumumab, ~30 days after last dose of study drug, and 4 months after last dose of study drug (Up to ~13.3 months) |
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| Secondary | Time to Maximum Observed Concentration (Tmax) of Robatumumab | Tmax was defined as time of Cmax of robatumumab when administered in combination with other treatments. Blood samples for analysis of robatumumab PK were to be obtained at Cycles 1 and 2 at the following time points: predose, immediately post-infusion, and at 3, 6, 24, 48, 168, 336, and 504 hours post the start time of infusion. For all odd-numbered cycles (Cycle 3 and on) samples were to be obtained at each of the following two time points: predose and immediately postdose of robatumumab. Additionally, PK samples were to be obtained at the Post Study Visits 1 (30 days after last dose of robatumumab or standard treatment and 2 (approximately 4 months after last dose of robatumumab or standard treatment). | All Treated Set was defined as all participants who received ≥1 dose of robatumumab or chemotherapy. Individual data were collected, but, due to study termination and small numbers of participants, summary data for Tmax were not produced. | Posted | Cycles 1 & 2: pre- and post-infusion, and at 3, 6, 24, 48, 168, 336, and 504 hours post start of infusion; then pre-and post-dose in odd-numbered cycles, and Post Study Visits 1 and 2 |
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| Secondary | Area Under the Curve at the Time of Final Quantifiable Sample (AUCtf) for Robatumumab | AUCtf for robatumumab was defined as the area under the curve at the time of the final quantifiable sample of robatumumab. Blood samples for analysis of robatumumab PK were to be obtained at Cycles 1 and 2 at the following time points: predose, immediately post-infusion, and at 3, 6, 24, 48, 168, 336, and 504 hours post the start time of infusion. For all odd-numbered cycles (Cycle 3 and on) samples were to be obtained at each of the following two time points: predose and immediately postdose of robatumumab. Additionally, PK samples were to be obtained at the Post Study Visits 1 (30 days after last dose of robatumumab or standard treatment and 2 (approximately 4 months after last dose of robatumumab or standard treatment). | All Treated Set was defined as all participants who received ≥1 dose of robatumumab or chemotherapy. Individual data were collected, but, due to study termination and small numbers of participants, summary data for AUCtf were not produced. | Posted | Cycles 1 & 2: pre- and post-infusion, and at 3, 6, 24, 48, 168, 336, and 504 hours post start of infusion; then pre-and post-dose in odd-numbered cycles, and Post Study Visits 1 and 2 |
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| Secondary | Area Under the Curve During a Dosing Interval τ (AUCτ) for Robatumumab | AUCτ was defined as the area under the plasma concentration-time curve during a dosage interval (τ). Blood samples for analysis of robatumumab PK were to be obtained at Cycles 1 and 2 at the following time points: predose, immediately post-infusion, and at 3, 6, 24, 48, 168, 336, and 504 hours post the start time of infusion. For all odd-numbered cycles (Cycle 3 and on) samples were to be obtained at each of the following two time points: predose and immediately postdose of robatumumab. Additionally, PK samples were to be obtained at the Post Study Visits 1 (30 days after last dose of robatumumab or standard treatment and 2 (approximately 4 months after last dose of robatumumab or standard treatment). | All Treated Set was defined as all participants who received ≥1 dose of robatumumab or chemotherapy. Individual data were collected, but, due to study termination and small numbers of participants, summary data for AUCτ were not produced. | Posted | Cycles 1 & 2: pre- and post-infusion, and at 3, 6, 24, 48, 168, 336, and 504 hours post start of infusion; then pre-and post-dose in odd-numbered cycles, and Post Study Visits 1 and 2 |
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| Secondary | Plasma Level of Insulin-like Growth Factor-2 (IGF-II) | IGF-II is generally produced locally in response to growth hormone from the hypothalamic-pituitary axis. The IGF ligands can promote neoplastic events (cancer growth) through a number of different mechanisms. Robatumumab inhibits IGF ligand binding, IGF-stimulated receptor phosphorylation and human tumor cell proliferation. Plasma levels of IGF-II were to be analyzed on Day 1 of Cycles 1, 2, 3, 5, and approximately 30 days after the final dose of robatumumab or the standard treatment assigned (whichever was last). | All Treated Set was defined as all participants who received ≥1 dose of robatumumab or chemotherapy. Individual data were collected, but, due to study termination and small numbers of participants, summary data for IGF-II were not produced. | Posted | On Day 1 of Cycles 1, 2, 3 and 5, and ~30 days after last dose of study drug (Up to~10.3 months) |
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| Secondary | Plasma Level of Insulin-like Growth Factor Binding Protein-2 (IGFBP-2) | The IGFBP-2 protein is secreted into the bloodstream where it binds to IGF-I and IGF-II. High expression levels of this protein promote the growth of several types of tumors and may be predictive of the chances of recovery of the participant. Robatumumab inhibits expression of this protein. Plasma levels of IGFBP-2 were to be analyzed on Day 1 of Cycles 1, 2, 3, 5, and approximately 30 days after the final dose of robatumumab or the standard treatment assigned (whichever was last). | All Treated Set was defined as all participants who received ≥1 dose of robatumumab or chemotherapy. Individual data were collected, but, due to study termination and small numbers of participants, summary data for IGFBP-2 were not produced. | Posted | On Day 1 of Cycles 1, 2, 3 and 5, and ~30 days after last dose of study drug (Up to~10.3 months) |
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| Secondary | Plasma Level of Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) | The IGFBP-3 protein is secreted into the bloodstream where it binds to IGF-I and IGF-II. High expression levels of this protein promote the growth of several types of tumors and may be predictive of the chances of recovery of the participant. Robatumumab inhibits expression of this protein. Plasma levels of IGFBP-3 were to be analyzed on Day 1 of Cycles 1, 2, 3, 5, and approximately 30 days after the final dose of robatumumab or the standard treatment assigned (whichever was last). | All Treated Set was defined as all participants who received ≥1 dose of robatumumab or chemotherapy. Individual data were collected, but, due to study termination and small numbers of participants, summary data for IGFBP-3 were not produced. | Posted | On Day 1 of Cycles 1, 2, 3 and 5, and ~30 days after last dose of study drug (Up to~10.3 months) |
|
Up to 30 days after last dose of study drug (Up to ~10.3 months)
All Treated Set was defined as all participants who received ≥1 dose of robatumumab or chemotherapy.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Temozolomide+Irinotecan+Robatumumab | Participants receive temozolomide 100 mg/m^2/day IV on Days 1-5 PLUS irinotecan 10 mg/m^2/day IV on Days 1-5 and Days 8-12 PLUS robatumumab 10 mg/kg or 20 mg/kg IV on Day 1 of each 3-week cycle. | 0 | 1 | 1 | 1 | ||
| EG001 | Vincristine+Doxorubicin+Cyclophosphamide+Robatumumab | Participants receive vincristine 2 mg/m^2 (maximum 2 mg) IV on Day 1 PLUS cyclophosphamide 1200 mg/m^2 IV on Day 1 PLUS doxorubicin hydrochloride 75 mg/m^2 IV continuously over 48 hours PLUS robatumumab 10 mg/kg or 20 mg/kg IV on Day 1 of each 3-week cycle. | 0 | 0 | 0 | 0 | ||
| EG002 | Ifosfamide+Etoposide+Robatumumab | Participants receive ifosfamide 1800 mg/m^2 per day IV PLUS etoposide 100 mg/m^2 per day IV on Days 1-5 PLUS robatumumab 10 mg/kg or 20 mg/kg IV on Day 1 of each 3-week cycle. | 3 | 3 | 3 | 3 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Chills | General disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Lobar pneumonia | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
| |
| Transfusion reaction | Injury, poisoning and procedural complications | MedDRA 13.1 | Systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA 13.1 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA 13.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Lymphopenia | Blood and lymphatic system disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Thromobocytopenia | Blood and lymphatic system disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Ear pain | Ear and labyrinth disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Adrenal insufficiency | Endocrine disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Haemorrhoids | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Oral disorder | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Cyst | General disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Mass | General disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Mucosal inflammation | General disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Pain | General disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Otitis media | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
| |
| Lymphocyte count decreased | Investigations | MedDRA 13.1 | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA 13.1 | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA 13.1 | Systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA 13.1 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Groin pain | Musculoskeletal and connective tissue disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Muscle twitching | Musculoskeletal and connective tissue disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Sinus headache | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Glycosuria | Renal and urinary disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Respiratory distress | Respiratory, thoracic and mediastinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Acne | Skin and subcutaneous tissue disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 13.1 | Systematic Assessment |
|
The investigator agrees to provide to the sponsor 45 days prior to submission for publication or presentation, review copies of abstracts or manuscripts for publication that report any results of the trial.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp. | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
| ID | Term |
|---|---|
| D009369 | Neoplasms |
| D001859 | Bone Neoplasms |
| D002292 | Carcinoma, Renal Cell |
| D009447 | Neuroblastoma |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D001847 | Bone Diseases |
| D009140 | Musculoskeletal Diseases |
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D007680 | Kidney Neoplasms |
| D014571 | Urologic Neoplasms |
| D014565 | Urogenital Neoplasms |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052801 | Male Urogenital Diseases |
| D018241 | Neuroectodermal Tumors, Primitive, Peripheral |
| D018242 | Neuroectodermal Tumors, Primitive |
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009380 | Neoplasms, Nerve Tissue |
Not provided
Not provided
| ID | Term |
|---|---|
| D000077204 | Temozolomide |
| D014750 | Vincristine |
| D007069 | Ifosfamide |
| D000077146 | Irinotecan |
| C573312 | robatumumab |
| D004317 | Doxorubicin |
| D003520 | Cyclophosphamide |
| D005047 | Etoposide |
| ID | Term |
|---|---|
| D003606 | Dacarbazine |
| D014226 | Triazenes |
| D009930 | Organic Chemicals |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D014748 | Vinca Alkaloids |
| D046948 | Secologanin Tryptamine Alkaloids |
| D026121 | Indole Alkaloids |
| D000470 | Alkaloids |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D054836 | Indolizidines |
| D007212 | Indolizines |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D010078 | Oxazines |
| D002166 | Camptothecin |
| D003630 | Daunorubicin |
| D018943 | Anthracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D011083 | Polycyclic Compounds |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D011034 | Podophyllotoxin |
| D013764 | Tetrahydronaphthalenes |
| D009281 | Naphthalenes |
| D005960 | Glucosides |
Not provided
Not provided
| Male |
|
Participants receive vincristine 2 mg/m^2 (maximum 2 mg) IV on Day 1 PLUS cyclophosphamide 1200 mg/m^2 IV on Day 1 PLUS doxorubicin hydrochloride 75 mg/m^2 IV continuously over 48 hours PLUS robatumumab 10 mg/kg or 20 mg/kg IV on Day 1 of each 3-week cycle.
| OG002 | Ifosfamide+Etoposide+Robatumumab | Participants receive ifosfamide 1800 mg/m^2 per day IV PLUS etoposide 100 mg/m^2 per day IV on Days 1-5 PLUS robatumumab 10 mg/kg or 20 mg/kg IV on Day 1 of each 3-week cycle. |
|
|
Participants receive vincristine 2 mg/m^2 (maximum 2 mg) IV on Day 1 PLUS cyclophosphamide 1200 mg/m^2 IV on Day 1 PLUS doxorubicin hydrochloride 75 mg/m^2 IV continuously over 48 hours PLUS robatumumab 10 mg/kg or 20 mg/kg IV on Day 1 of each 3-week cycle. |
| OG002 | Ifosfamide+Etoposide+Robatumumab | Participants receive ifosfamide 1800 mg/m^2 per day IV PLUS etoposide 100 mg/m^2 per day IV on Days 1-5 PLUS robatumumab 10 mg/kg or 20 mg/kg IV on Day 1 of each 3-week cycle. |
|
| OG002 | Ifosfamide+Etoposide+Robatumumab | Participants receive ifosfamide 1800 mg/m^2 per day IV PLUS etoposide 100 mg/m^2 per day IV on Days 1-5 PLUS robatumumab 10 mg/kg or 20 mg/kg IV on Day 1 of each 3-week cycle. |
|
| OG002 | Ifosfamide+Etoposide+Robatumumab | Participants receive ifosfamide 1800 mg/m^2 per day IV PLUS etoposide 100 mg/m^2 per day IV on Days 1-5 PLUS robatumumab 10 mg/kg or 20 mg/kg IV on Day 1 of each 3-week cycle. |
|
|
Participants receive vincristine 2 mg/m^2 (maximum 2 mg) IV on Day 1 PLUS cyclophosphamide 1200 mg/m^2 IV on Day 1 PLUS doxorubicin hydrochloride 75 mg/m^2 IV continuously over 48 hours PLUS robatumumab 10 mg/kg or 20 mg/kg IV on Day 1 of each 3-week cycle. |
| OG002 | Ifosfamide+Etoposide+Robatumumab | Participants receive ifosfamide 1800 mg/m^2 per day IV PLUS etoposide 100 mg/m^2 per day IV on Days 1-5 PLUS robatumumab 10 mg/kg or 20 mg/kg IV on Day 1 of each 3-week cycle. |
|
Participants receive vincristine 2 mg/m^2 (maximum 2 mg) IV on Day 1 PLUS cyclophosphamide 1200 mg/m^2 IV on Day 1 PLUS doxorubicin hydrochloride 75 mg/m^2 IV continuously over 48 hours PLUS robatumumab 10 mg/kg or 20 mg/kg IV on Day 1 of each 3-week cycle. |
| OG002 | Ifosfamide+Etoposide+Robatumumab | Participants receive ifosfamide 1800 mg/m^2 per day IV PLUS etoposide 100 mg/m^2 per day IV on Days 1-5 PLUS robatumumab 10 mg/kg or 20 mg/kg IV on Day 1 of each 3-week cycle. |
|
Participants receive vincristine 2 mg/m^2 (maximum 2 mg) IV on Day 1 PLUS cyclophosphamide 1200 mg/m^2 IV on Day 1 PLUS doxorubicin hydrochloride 75 mg/m^2 IV continuously over 48 hours PLUS robatumumab 10 mg/kg or 20 mg/kg IV on Day 1 of each 3-week cycle. |
| OG002 | Ifosfamide+Etoposide+Robatumumab | Participants receive ifosfamide 1800 mg/m^2 per day IV PLUS etoposide 100 mg/m^2 per day IV on Days 1-5 PLUS robatumumab 10 mg/kg or 20 mg/kg IV on Day 1 of each 3-week cycle. |
|
| OG002 | Ifosfamide+Etoposide+Robatumumab | Participants receive ifosfamide 1800 mg/m^2 per day IV PLUS etoposide 100 mg/m^2 per day IV on Days 1-5 PLUS robatumumab 10 mg/kg or 20 mg/kg IV on Day 1 of each 3-week cycle. |
|
| OG002 | Ifosfamide+Etoposide+Robatumumab | Participants receive ifosfamide 1800 mg/m^2 per day IV PLUS etoposide 100 mg/m^2 per day IV on Days 1-5 PLUS robatumumab 10 mg/kg or 20 mg/kg IV on Day 1 of each 3-week cycle. |
|
| OG002 | Ifosfamide+Etoposide+Robatumumab | Participants receive ifosfamide 1800 mg/m^2 per day IV PLUS etoposide 100 mg/m^2 per day IV on Days 1-5 PLUS robatumumab 10 mg/kg or 20 mg/kg IV on Day 1 of each 3-week cycle. |
|