Neoplasms

All Conditions

Musculoskeletal Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Osteosarcoma

Neuroblastoma

Bone Neoplasms

Kidney Neoplasms

Neuroectodermal Tumors, Primitive, Peripheral

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Neuroepithelial

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Bone Diseases

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Anti-Infective Agents

Etoposide

Cyclophosphamide

Irinotecan

Doxorubicin

Liposomal doxorubicin

Temozolomide

Vincristine

Ifosfamide

Etoposide phosphate

Isophosphamide mustard

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Topoisomerase I Inhibitors

Tubulin Modulators

Antimitotic Agents

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.

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.

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.

Robatumumab

Medical Director

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.

A Study of Robatumumab (SCH 717454, MK-7454) in Combination With Different Treatment Regimens in Pediatric Participants With Advanced Solid Tumors (P05883, MK-7454-006)

A Phase 1/1B Dose-Escalation Study to Determine the Safety and Tolerability of SCH 717454 Administered in Combination With Chemotherapy in Pediatric Subjects With Advanced Solid Tumors (Protocol No. 05883)

https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

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 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.

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).

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).

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.

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).

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).

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).

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).

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).

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).

Merck Sharp & Dohme LLC

All Treated Set was defined as all participants who received ≥1 dose of robatumumab or chemotherapy.

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.

Temozolomide+Irinotecan+Robatumumab

Vincristine+Doxorubicin+Cyclophosphamide+Robatumumab

Ifosfamide+Etoposide+Robatumumab

Total

Age, Continuous

Sex: Female, Male

Senior Vice President, Global Clinical Development

Number of Participants With Dose Limiting Toxicities

Complete Response (CR)

Partial Response (PR)

Stable Disease (SD)

Progressive Disease (PD)

Best Overall Response Based on Response Evaluation Criteria in Solid Tumors (RECIST)

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.

Maximum Observed Concentration (Cmax) of Robatumumab

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.

Plasma Level of Insulin-like Growth Factor-I (IGF-I)

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.

Number of Participants Who Developed Anti-robatumumab Antibodies

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.

Time to Maximum Observed Concentration (Tmax) of Robatumumab

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.

Area Under the Curve at the Time of Final Quantifiable Sample (AUCtf) for Robatumumab

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.

Area Under the Curve During a Dosing Interval τ (AUCτ) for Robatumumab

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.

Plasma Level of Insulin-like Growth Factor-2 (IGF-II)

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.

Plasma Level of Insulin-like Growth Factor Binding Protein-2 (IGFBP-2)

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.

Plasma Level of Insulin-like Growth Factor Binding Protein-3 (IGFBP-3)

Overall Study

Micronutrients

Hematinics

Vitamins

Antibodies

Gemcitabine

Trastuzumab

Paclitaxel

Carboplatin

Cetuximab

Leucovorin

Fluorouracil

Levoleucovorin

Everolimus

Albumin-Bound Paclitaxel

Cisplatin

Epirubicin

Sirolimus

Folic Acid

Immunoglobulins

Mitogens

Erlotinib Hydrochloride

Temsirolimus

MTOR Inhibitors

Vitamin B Complex

Antimetabolites

Antineoplastic Agents, Immunological

Protein Kinase Inhibitors

Antidotes

Protective Agents

Trace Elements

Folinic Acid

Folate

Vitamin B9

Participants with colorectal adenocarcinoma receive FOLFIRI (Irinotecan 180 mg/m\^2+ folinic acid 400 mg/m\^2+ 5-fluorouracil \[5-FU\] 400 mg/m\^2 bolus followed by 2400 mg/m\^2 intravenous \[IV\] infusion over 46 hours) (± cetuximab initial dose of 400 mg/m\^2 IV followed by once-weekly doses of 250 mg/m\^2 IV) PLUS robatumumab 10 mg/kg or 20 mg/kg IV on Day 1 of each 2-week cycle.

Participants with non-small cell lung cancer receive carboplatin administered at an area under the curve (AUC) of 6 mg/mL/min IV PLUS paclitaxel 225 mg/m\^2 IV PLUS robatumumab 15 mg/kg IV on Day 1 of each 3-week cycle.

Participants with gastric adenocarcinoma receive epirubicin 50 mg/m\^2 IV PLUS cisplatin 60 mg/m\^2 IV PLUS 5-FU 200 mg/m\^2/day administered via a 21-week continuous IV infusion PLUS robatumumab 15 mg/kg IV on Day 1 of each 3-week cycle.

Participants with human epidermal growth factor receptor 2 positive (Her2+) breast cancer receive trastuzumab 4 mg/kg IV once every week PLUS robatumumab 10 mg/kg or 20 mg/kg IV on Day 1 of each 4-week cycle.

Participants with renal cell cancer receive mammalian target of rapamycin (mTor) inhibitor (everolimus) 10 mg orally once per day PLUS robatumumab 10 mg/kg or 20 mg/kg IV on Day 1 of each 4-week cycle.

Participants with pancreatic adenocarcinoma receive gemcitabine 1000 mg/m\^2 IV on Days 1, 8, 15, 22, 29, 36, and 43 in Cycle 1 and on Days 1, 8 and 15 in subsequent cycles (± erlotinib 100 mg per day orally) PLUS robatumumab 10 mg/kg or 20 mg/kg IV on Day 1 of each 4-week cycle. (Cycle 1 is 8 weeks.)

In Part 1, robatumumab was to be administered at 10 mg/kg, 15 mg/kg (for Regimens B and C), or 20 mg/kg together with the assigned standard treatment. For Part 2, robatumumab was to be administered at the dose selected during Part 1, based upon the maximum tolerated dose (MTD) or maximum administered dose (MAD), pharmacokinetic (PK) and pharmacodynamic (PD) data.

5-FU

Erlotinib

This is a Phase 1B/2, non-randomized, dose-escalation, multicenter, open-label study designed to evaluate the safety and tolerability of robatumumab (SCH 717454, MK-7454) in combination with standard treatment in participants with advanced solid tumors to be conducted in conformance with Good Clinical Practices.

Six different treatment regimens will be investigated in combination with robatumumab.

The study will be divided into two parts. Part 1 will consist of initial safety evaluation and dose-finding of robatumumab in combination with each treatment regimen. Part 2 will consist of an expansion of each robatumumab regimen at a newly established dose level, to better define safety, tolerability, and initial efficacy in specific target populations.

Study of Robatumumab (SCH 717454, MK-7454) in Combination With Different Treatment Regimens in Participants With Advanced Solid Tumors (P04722, MK-7454-004)

A Dose-Escalation Study to Evaluate the Safety and Tolerability of SCH 717454 in Combination With Different Treatment Regimens in Subjects With Advanced Solid Tumors (Phase 1B/2; Protocol No. P04722)

Overall best response was determined by RECIST criteria. Types of overall response could be: Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive Disease (PD), Not Assessable (NA) or Incomplete Response/Stable Disease (IR/SD).

An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to this study drug. AEs may include the onset of new illness and the exacerbation of pre-existing conditions.

The All Treated Set consisted of all participants who received ≥1 dose of study drug.

Participants with colorectal adenocarcinoma receive FOLFIRI (Irinotecan 180 mg/m\^2+ folinic acid 400 mg/m\^2+ 5-FU 400 mg/m\^2 bolus followed by 2400 mg/m\^2 IV infusion over 46 hours) (± cetuximab initial dose of 400 mg/m\^2 followed by once-weekly doses of 250 mg/m\^2) PLUS robatumumab 10 mg/kg or 20 mg/kg IV. Each cycle is 2 weeks.

Regimen A: FOLFIRI (+/- Cetuximab) + Robatumumab

Participants with non-small cell lung cancer receive carboplatin administered at an AUC of 6 mg/mL/min IV PLUS paclitaxel 225 mg/m\^2 IV PLUS robatumumab 15 mg/kg IV on Day 1 of each 3-week cycle.

Regimen B: Carboplatin + Paclitaxel + Robatumumab

Participants with Her2+ breast cancer receive trastuzumab 4 mg/kg IV once every week PLUS robatumumab 10 mg/kg or 20 mg/kg IV on Day 1 of each 4-week cycle.

Regimen D: Trastuzumab + Robatumumab

Participants with renal cell cancer receive mTor inhibitor (everolimus) 10 mg orally once per day PLUS robatumumab 10 mg/kg or 20 mg/kg IV on Day 1 of each 4-week cycle.

Regimen E: mTor Inhibitor (Everolimus) + Robatumumab

Participants with pancreatic adenocarcinoma receive gemcitabine 1000 mg/m\^2 on Days 1, 8, 15, 22, 29, 36, and 43 (± erlotinib 100 mg per day) PLUS robatumumab 10 mg/kg or 20 mg/kg IV. Each cycle is 8 weeks.

Regimen F: Gemcitabine (+/- Erlotinib) + Robatumumab

Participants with colorectal adenocarcinoma receive FOLFIRI (Irinotecan 180 mg/m\^2+ folinic acid 400 mg/m\^2+ 5-FU 400 mg/m\^2 bolus followed by 2400 mg/m\^2 IV infusion over 46 hours) (± cetuximab initial dose of 400 mg/m\^2 IV followed by once-weekly doses of 250 mg/m\^2 IV) PLUS robatumumab 10 mg/kg or 20 mg/kg IV on Day 1 of each 2-week cycle.

Regimen A: FOLFIRI (± Cetuximab) + Robatumumab

Regimen C: Epirubicin + Cisplatin + 5-FU + Robatumumab

Regimen F: Gemcitabine (± Erlotinib) + Robatumumab

Not Assessable (NA)

Incomplete Response/Stable Disease (IR/SD)

The All Treated Set (efficacy) consisted of all participants who received ≥1 dose of study drug and were evaluable for this outcome measure.

Part 2: Number of Participants With Each Type of Response Evaluation Criteria in Solid Tumors (RECIST)-Determined Overall Best Response

The All Treated Set (safety) consisted of all participants who received ≥1 dose of study drug.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Robatumumab (SCH 717454, MK-7454) in Combination With Different Treatment Regimens in Pediatric Participants With Advanced Solid Tumors (P05883, MK-7454-006)	NCT00960063	Neoplasms Solid Tumors Bone Cancer Kidney Tumor Neuroblastoma	Temozolomide Vincristine Ifosfamide Irinotecan Robatumumab Doxorubicin Cyclophosphamid... Etoposide	- 21 Years	Merck Sharp & Dohme LLC
A Study of Robatumumab (SCH 717454, MK-7454) in Combination With Different Treatment Regimens in Pediatric Participants With Advanced Solid Tumors (P05883, MK-7454-006)	NCT00960063	Neoplasms Solid Tumors Bone Cancer Kidney Tumor Neuroblastoma	Temozolomide Vincristine Ifosfamide Irinotecan Robatumumab Doxorubicin Cyclophosphamid... Etoposide	- 21 Years	Merck Sharp & Dohme LLC
Study of Robatumumab (SCH 717454, MK-7454) in Combination With Different Treatment Regimens in Participants With Advanced Solid Tumors (P04722, MK-7454-004)	NCT00954512	Neoplasms	Carboplatin Epirubicin Trastuzumab Everolimus Gemcitabine Robatumumab Cetuximab Paclitaxel Cisplatin 5-FU Erlotinib Irinotecan Folinic Acid	18 Years -	Merck Sharp & Dohme LLC

Spots Global Cancer Trial Database for robatumumab

Every month we try and update this database with for robatumumab cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for robatumumab

Every month we try and update this database with for robatumumab cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for robatumumab cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.