Study of Robatumumab (SCH 717454, MK-7454) in Combination With Different Treatment Regimens in Participants With Advanced Solid Tumors (P04722, MK-7454-004)
Phase 1
Terminated
- Conditions
- Neoplasms
- Interventions
- Biological: RobatumumabBiological: TrastuzumabBiological: Cetuximab
- Registration Number
- NCT00954512
- Lead Sponsor
- Merck Sharp & Dohme LLC
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 15
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Regimen A: FOLFIRI (± Cetuximab) + Robatumumab 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. Regimen A: FOLFIRI (± Cetuximab) + Robatumumab 5-FU 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. Regimen A: FOLFIRI (± Cetuximab) + Robatumumab Cetuximab 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. Regimen E: mTor Inhibitor (Everolimus) + Robatumumab 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. Regimen D: Trastuzumab + Robatumumab Trastuzumab 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. Regimen B: Carboplatin + Paclitaxel + Robatumumab 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. Regimen D: Trastuzumab + Robatumumab 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. Regimen C: Epirubicin + Cisplatin + 5-FU + Robatumumab 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. Regimen F: Gemcitabine (± Erlotinib) + Robatumumab Erlotinib 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.) Regimen F: Gemcitabine (± Erlotinib) + Robatumumab 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.) Regimen A: FOLFIRI (± Cetuximab) + Robatumumab Irinotecan 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. Regimen A: FOLFIRI (± Cetuximab) + Robatumumab Folinic Acid 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. Regimen B: Carboplatin + Paclitaxel + Robatumumab Carboplatin 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. Regimen C: Epirubicin + Cisplatin + 5-FU + Robatumumab Epirubicin 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. Regimen B: Carboplatin + Paclitaxel + Robatumumab Paclitaxel 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. Regimen C: Epirubicin + Cisplatin + 5-FU + Robatumumab 5-FU 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. Regimen C: Epirubicin + Cisplatin + 5-FU + Robatumumab Cisplatin 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. Regimen E: mTor Inhibitor (Everolimus) + Robatumumab Everolimus 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. Regimen F: Gemcitabine (± Erlotinib) + Robatumumab Gemcitabine 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.)
- Primary Outcome Measures
Name Time Method Part 2: Number of Participants With Each Type of Response Evaluation Criteria in Solid Tumors (RECIST)-Determined Overall Best Response Up to ~30 days after the final dose of robatumumab (Up to ~14 months) 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).
Part 1: Number of Participants Who Experienced One or More Adverse Events (AEs) Up to ~30 days after the final dose of robatumumab (Up to ~14 months) 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.
- Secondary Outcome Measures
Name Time Method