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

NCT00954512 | Terminated Phase 1 Results

• 3 other identifiers: P04722MK-7454-0042009-011101-16
• Study Type: interventional
• Target: 15
• Locations: 0 countries
• Sites: N/A

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

Keywords

Antibodies, neoplasm

Outcome Measures

Primary Outcomes (2)

• 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)

Study Arms (6)

Regimen A: FOLFIRI (± Cetuximab) + Robatumumab

EXPERIMENTAL

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; Biological: Cetuximab; Drug: 5-FU; Drug: Irinotecan; Drug: Folinic Acid

Regimen B: Carboplatin + Paclitaxel + Robatumumab

EXPERIMENTAL

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; Biological: Robatumumab; Drug: Paclitaxel

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

EXPERIMENTAL

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; Biological: Robatumumab; Drug: Cisplatin; Drug: 5-FU

Regimen D: Trastuzumab + Robatumumab

EXPERIMENTAL

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; Biological: Robatumumab

Regimen E: mTor Inhibitor (Everolimus) + Robatumumab

EXPERIMENTAL

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; Biological: Robatumumab

Regimen F: Gemcitabine (± Erlotinib) + Robatumumab

EXPERIMENTAL

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; Biological: Robatumumab; Drug: Erlotinib

Interventions

Carboplatin DRUG

Regimen B: Carboplatin + Paclitaxel + Robatumumab

Epirubicin DRUG

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

Trastuzumab BIOLOGICAL

Regimen D: Trastuzumab + Robatumumab

Everolimus DRUG

Regimen E: mTor Inhibitor (Everolimus) + Robatumumab

Gemcitabine DRUG

Regimen F: Gemcitabine (± Erlotinib) + Robatumumab

Robatumumab 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 A: FOLFIRI (± Cetuximab) + Robatumumab; Regimen B: Carboplatin + Paclitaxel + Robatumumab; Regimen C: Epirubicin + Cisplatin + 5-FU + Robatumumab; Regimen D: Trastuzumab + Robatumumab; Regimen E: mTor Inhibitor (Everolimus) + Robatumumab; Regimen F: Gemcitabine (± Erlotinib) + Robatumumab

Cetuximab BIOLOGICAL

Regimen A: FOLFIRI (± Cetuximab) + Robatumumab

Paclitaxel DRUG

Regimen B: Carboplatin + Paclitaxel + Robatumumab

Cisplatin DRUG

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

5-FU DRUG

Regimen A: FOLFIRI (± Cetuximab) + Robatumumab; Regimen C: Epirubicin + Cisplatin + 5-FU + Robatumumab

Erlotinib DRUG

Regimen F: Gemcitabine (± Erlotinib) + Robatumumab

Irinotecan DRUG

Regimen A: FOLFIRI (± Cetuximab) + Robatumumab

Folinic Acid DRUG

Regimen A: FOLFIRI (± Cetuximab) + Robatumumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

MeSH Terms

Conditions

Neoplasms

Interventions

Carboplatin; Epirubicin; Trastuzumab; Everolimus; Gemcitabine; robatumumab; Cetuximab; Paclitaxel; Cisplatin; Fluorouracil; Erlotinib Hydrochloride; Irinotecan; Leucovorin

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Doxorubicin; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sirolimus; Macrolides; Lactones; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Uracil; Pyrimidinones; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Camptothecin; Alkaloids; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Coenzymes; Enzymes and Coenzymes

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2009
• First Posted: August 7, 2009
• Study Start: September 25, 2009
• Primary Completion: June 7, 2011
• Study Completion: June 7, 2011
• Last Updated: August 24, 2018
• Results First Posted: December 22, 2015

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will share