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

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Neoplasms

Intervention / Treatment
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* Drug: Carboplatin
* Drug: Epirubicin
* Biological: Trastuzumab
* Drug: Everolimus
* Drug: Gemcitabine
* Biological: Robatumumab
* Biological: Cetuximab
* Drug: Paclitaxel
* Drug: Cisplatin
* Drug: 5-FU
* Drug: Erlotinib
* Drug: Irinotecan
* Drug: Folinic Acid


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Regimen A: FOLFIRI (± Cetuximab) + Robatumumab<br>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. | Biological: Robatumumab<br>* 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.<br>Biological: Cetuximab<br> <br> Drug: 5-FU<br> <br> Drug: Irinotecan<br> <br> Drug: Folinic Acid<br> <br> |
| Experimental: Regimen B: Carboplatin + Paclitaxel + Robatumumab<br>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. | Drug: Carboplatin<br> <br> Biological: Robatumumab<br>* 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.<br>Drug: Paclitaxel<br> <br> |
| Experimental: Regimen C: Epirubicin + Cisplatin + 5-FU + Robatumumab<br>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. | Drug: Epirubicin<br> <br> Biological: Robatumumab<br>* 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.<br>Drug: Cisplatin<br> <br> Drug: 5-FU<br> <br> |
| Experimental: Regimen D: Trastuzumab + Robatumumab<br>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. | Biological: Trastuzumab<br> <br> Biological: Robatumumab<br>* 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.<br>|
| Experimental: Regimen E: mTor Inhibitor (Everolimus) + Robatumumab<br>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. | Drug: Everolimus<br> <br> Biological: Robatumumab<br>* 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.<br>|
| Experimental: Regimen F: Gemcitabine (± Erlotinib) + Robatumumab<br>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.) | Drug: Gemcitabine<br> <br> Biological: Robatumumab<br>* 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.<br>Drug: Erlotinib<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 2: Number of Participants With Each Type of Response Evaluation Criteria in Solid Tumors (RECIST)-Determined Overall Best Response | 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). | Up to  30 days after the final dose of robatumumab (Up to  14 months) | 
| Part 1: Number of Participants Who Experienced One or More Adverse Events (AEs) | 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. | Up to  30 days after the final dose of robatumumab (Up to  14 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Antibodies, neoplasm