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

NCT ID: NCT00954512

Last Updated: 2018-08-24

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-09-25
• Study Completion Date: 2011-06-07

Brief Summary

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.

Conditions

Neoplasms

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Regimen A: FOLFIRI (± Cetuximab) + Robatumumab

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.

Group Type: EXPERIMENTAL

Robatumumab

Intervention Type: BIOLOGICAL

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.

Cetuximab

Intervention Type: BIOLOGICAL

5-FU

Intervention Type: DRUG

Irinotecan

Intervention Type: DRUG

Folinic Acid

Intervention Type: DRUG

Regimen B: Carboplatin + Paclitaxel + Robatumumab

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.

Group Type: EXPERIMENTAL

Carboplatin

Intervention Type: DRUG

Robatumumab

Intervention Type: BIOLOGICAL

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.

Paclitaxel

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

Epirubicin

Intervention Type: DRUG

Robatumumab

Intervention Type: BIOLOGICAL

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.

Cisplatin

Intervention Type: DRUG

5-FU

Intervention Type: DRUG

Regimen D: Trastuzumab + Robatumumab

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.

Group Type: EXPERIMENTAL

Trastuzumab

Intervention Type: BIOLOGICAL

Robatumumab

Intervention Type: BIOLOGICAL

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.

Regimen E: mTor Inhibitor (Everolimus) + Robatumumab

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.

Group Type: EXPERIMENTAL

Everolimus

Intervention Type: DRUG

Robatumumab

Intervention Type: BIOLOGICAL

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.

Regimen F: Gemcitabine (± Erlotinib) + Robatumumab

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.)

Group Type: EXPERIMENTAL

Gemcitabine

Intervention Type: DRUG

Robatumumab

Intervention Type: BIOLOGICAL

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.

Erlotinib

Intervention Type: DRUG

Interventions

Carboplatin

Intervention Type: DRUG

Epirubicin

Intervention Type: DRUG

Trastuzumab

Intervention Type: BIOLOGICAL

Everolimus

Intervention Type: DRUG

Gemcitabine

Intervention Type: DRUG

Robatumumab

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.

Intervention Type: BIOLOGICAL

Cetuximab

Intervention Type: BIOLOGICAL

Paclitaxel

Intervention Type: DRUG

Cisplatin

Intervention Type: DRUG

5-FU

Intervention Type: DRUG

Erlotinib

Intervention Type: DRUG

Irinotecan

Intervention Type: DRUG

Folinic Acid

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Be willing and able to provide written informed consent for the study.
• Be ±18 years of age of either sex and of any race/ethnicity;
• Part 1: Have a histologically or cytologically confirmed advanced malignant solid tumor;
• Part 2: Have a histologically or cytologically confirmed, with measurable disease (as defined by Response Evaluation Criteria in Solid Tumors [RECIST]), advanced, malignant solid tumor.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of <=2.
• Have adequate organ function within 3 weeks prior to first study drug administration.

Exclusion Criteria

• Not have known treated or untreated leptomeningeal metastasis or a metastatic central nervous system lesion.
• Not have a history of another malignancy
• Not have received prior therapy with any anti-insulin-like growth factor receptor 1 (anti-IGF-1R) monoclonal antibody.
• Not have received radiation therapy within 2 weeks prior to first study drug administration.
• Not have received radiation therapy to >25% of his/her total bone marrow during his/her lifetime.
• Not have undergone major surgery within 3 weeks prior to first study drug administration.
• Not have known human immunodeficiency virus (HIV) infection or a known HIV-related malignancy.
• Not have known active hepatitis B or C.
• Not have any serious or uncontrolled infection.
• Not have uncontrolled diabetes mellitus.
• Not have had any of the following within 6 months prior to first study drug administration: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, clinically significant cardiac dysrhythmia or clinically significant electrocardiogram (ECG) abnormality, cerebrovascular accident or transient ischemic attack, or seizure disorder.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Study Documents

Document Type: CSR Synospsi Links

View Document

Other Identifiers

MK-7454-004

Identifier Type: OTHER

Identifier Source: secondary_id

2009-011101-16

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

P04722

Identifier Type: -

Identifier Source: org_study_id