NeoplasmsPhase 1/2NCT00954512
Study of Robatumumab (SCH 717454, MK-7454) in Combination With Different Treatment Regimens in Participants With Advanced Solid Tumors (P04722, MK-7454-004)
A Phase 1/2 study testing Carboplatin, Epirubicin and Trastuzumab in people with Neoplasms, run by Merck Sharp & Dohme LLC.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasms
- What is being tested?
- Carboplatin, Epirubicin and Trastuzumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- No sites listed yet
- Study dates
- 25 Sep 2009to 7 Jun 2011
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
About this study
Official title: 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)
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
- Being tested
- Carboplatin, Epirubicin, Trastuzumab, Everolimus, Gemcitabine
- Keywords
- Antibodies, neoplasm
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CarboplatinDrug
EpirubicinDrug
TrastuzumabBiological
EverolimusDrug
GemcitabineDrug
RobatumumabBiological
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.
CetuximabBiological
PaclitaxelDrug
CisplatinDrug
5-FUDrug
ErlotinibDrug
IrinotecanDrug
Folinic AcidDrug
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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.) Receives: Drug: Gemcitabine; Biological: Robatumumab; Drug: Erlotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Measured: Up to ~30 days after the final dose of robatumumab (Up to ~14 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2009 (estimated)
- Study start25 Sep 2009
- Primary completion7 Jun 2011
- Study completion7 Jun 2011
Why it stopped: This study was terminated for business reasons.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for NeoplasmsStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00954512
- Sponsor's protocol ID
- P04722
- Other IDs
- MK-7454-004, 2009-011101-16, 2009
- Status last verified
- Jul 2018
- First submitted
- 23 Jul 2009
- Last updated
- 24 Aug 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT00954512
- Acronym / sponsor ID
- P04722
- Conditions
- Neoplasms
- Keywords
- Antibodies, neoplasm
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: This study was terminated for business reasons.
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 25 Sep 2009 (actual)
- Primary completion
- 7 Jun 2011 (actual)
- Study completion
- 7 Jun 2011 (actual)
- First posted
- 7 Aug 2009 (estimated)
- Results
- Posted 22 Dec 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Regimen A: FOLFIRI (± Cetuximab) + Robatumumab | Experimental | Biological: Robatumumab, Biological: Cetuximab, Drug: 5-FU, Drug: Irinotecan, Drug: Folinic AcidParticipants 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 | Experimental | Drug: Carboplatin, Biological: Robatumumab, Drug: PaclitaxelParticipants 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 | Experimental | Drug: Epirubicin, Biological: Robatumumab, Drug: Cisplatin, Drug: 5-FUParticipants 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 D: Trastuzumab + Robatumumab | Experimental | Biological: Trastuzumab, Biological: RobatumumabParticipants 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 E: mTor Inhibitor (Everolimus) + Robatumumab | Experimental | Drug: Everolimus, Biological: RobatumumabParticipants 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 | Experimental | Drug: Gemcitabine, Biological: Robatumumab, Drug: ErlotinibParticipants 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.) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 |
| RobatumumabIn 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. | Biological | 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 |
Primary outcome
Part 2: Number of Participants With Each Type of Response Evaluation Criteria in Solid Tumors (RECIST)-Determined Overall Best Response
Time frame: 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)
Time frame: 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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Merck Sharp & Dohme LLC
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Carboplatin, Epirubicin and Trastuzumab in people with Neoplasms, run by Merck Sharp & Dohme LLC.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 24 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Dec 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part 2: Number of Participants With Each Type of Response Evaluation Criteria in Solid Tumors (RECIST)-Determined Overall Best Response (time frame: Up to ~30 days after the final dose of robatumumab (Up to ~14 months)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Aug 2018.