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

Merck Sharp & Dohme (MSD)

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Neoplasms

Treatments: Drug: Epirubicin; Drug: Gemcitabine; Drug: Carboplatin; Drug: Everolimus; Drug: 5-FU; Biological: Cetuximab; Drug: Irinotecan; Drug: Paclitaxel; Drug: Folinic Acid; Biological: Robatumumab; Drug: Cisplatin; Drug: Erlotinib; Biological: Trastuzumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT00954512

P04722

MK-7454-004 (Other Identifier)

2009-011101-16 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 15 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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15 participants in 6 patient groups

Regimen A: FOLFIRI (± Cetuximab) + Robatumumab

Experimental group

Description:

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.

Treatment:

Biological: Robatumumab

Drug: Irinotecan

Biological: Cetuximab

Drug: Folinic Acid

Drug: 5-FU

Regimen B: Carboplatin + Paclitaxel + Robatumumab

Experimental group

Description:

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.

Treatment:

Biological: Robatumumab

Drug: Paclitaxel

Drug: Carboplatin

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

Experimental group

Description:

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.

Treatment:

Biological: Robatumumab

Drug: Cisplatin

Drug: Epirubicin

Drug: 5-FU

Regimen D: Trastuzumab + Robatumumab

Experimental group

Description:

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.

Treatment:

Biological: Robatumumab

Biological: Trastuzumab

Regimen E: mTor Inhibitor (Everolimus) + Robatumumab

Experimental group

Description:

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.

Treatment:

Drug: Everolimus

Biological: Robatumumab

Regimen F: Gemcitabine (± Erlotinib) + Robatumumab

Experimental group

Description:

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.)

Treatment:

Biological: Robatumumab

Drug: Gemcitabine

Drug: Erlotinib