Rectal NeoplasmsPhase 2NCT01609231
A Trial of Dalotuzumab in Combination With Irinotecan Versus Cetuximab and Irinotecan for Participants With Metastatic Rectal Cancers (mRC) (MK-0646-025)
A Phase 2 study testing Dalotuzumab, Irinotecan and Cetuximab in people with Rectal Neoplasms, run by Merck Sharp & Dohme LLC.
Trial summary
The purpose of this adaptive trial is to compare the progression-free survival of participants with metastatic rectal carcinoma when treated with intravenous (IV) dalotuzumab (MK-0646) + irinotecan therapy relative to participants treated with IV cetuximab + irinotecan. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rectal Neoplasms
- What is being tested?
- Dalotuzumab, Irinotecan and Cetuximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- No sites listed yet
- Study dates
- 6 Jul 2012to 9 Dec 2014
- Phase
- Phase 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
- Has metastatic colorectal cancer with primary tumor originating from the rectum
- Has an available archival (recent or remote) tumor, or newly obtained formalin-fixed tissue available for analysis for biomarker studies
- Has at least one measurable lesion greater than or equal to 10 mm
- Disease has progressed after treatment with both irinotecan- and oxaliplatin-containing regimens and should have progressed on or within 3 months of completing their last line of therapy
- Has a performance status 0-1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
Who cannot join
- Has poorly-controlled diabetes
- Has received chemotherapy or biological therapy within 2 weeks prior to initial dosing on this study, or whose toxicities from agents administered 2 weeks earlier have not resolved to at least grade 1 or baseline, or who is within 3 weeks from a prior surgery
- Has received radiotherapy within 2 weeks prior to initial dosing on this study, unless the radiotherapy was for management of pain
- Is currently participating or has participated in a study with an investigational compound or device within 30 days or 5 half-lives of the investigational agent, whichever is longer, of initial dosing on this study
- Was unable to complete previous course of irinotecan due to intolerable toxicity, other than discontinuation due to fatigue following prolonged administration (>4 months exposure)
- Has prior exposure to insulin-like growth factor 1 receptor (IGF-1R) inhibitors or epidermal growth factor receptor (EGFR) inhibitors
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- Has a known central nervous system (CNS) metastases and/or carcinomatous meningitis
- Has primary CNS tumor
- Has a history of a prior malignancy with the exception of cervical intraepithelial neoplasia; basal cell carcinoma of the skin; adequately treated localized prostate carcinoma; potentially curative therapy with no evidence of that disease for 5 years, deemed low risk for recurrence by treating physician.
- Is human immunodeficiency virus (HIV)-positive
- Has active hepatitis B or C infection and is receiving antiviral treatment regimens
- Has symptomatic ascites or pleural effusion
- Is concurrently using growth hormone (GH), or growth hormone inhibitors
About this study
Official title: A Phase IIA Open Label, Adaptive, Randomized Clinical Trial of Dalotuzumab (MK-0646) Treatment in Combination With Irinotecan Versus Cetuximab and Irinotecan for Patients With Metastatic Rectal Cancers (mRC) Expressing High IGF-1/Low IGF-2 Levels
The purpose of this adaptive trial is to compare the progression-free survival of participants with metastatic rectal carcinoma when treated with intravenous (IV) dalotuzumab (MK-0646) + irinotecan therapy relative to participants treated with IV cetuximab + irinotecan. The primary hypothesis is that administration of dalotuzumab in combination with irinotecan to participants with wild-type KRAS metastatic rectal carcinoma with high insulin growth factor (IGF)-1/low IGF-2 expression levels improves progression-free survival compared to patients treated with cetuximab in combination with irinotecan.
- Conditions
- Rectal Neoplasms
- Being tested
- Dalotuzumab, Irinotecan, Cetuximab
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DalotuzumabDrug
Also called MK-0646
Dalotuzumab will be administered intravenously after the completion of irinotecan infusion at a dose of 10 mg/kg once weekly.
IrinotecanDrug
Also called Camptosar
Irinotecan 180 mg/m^2 will be administered intravenously once every two weeks either prior to dalotuzumab (Arm A) or after cetuximab (Arm B). Pre-medication at the discretion of the investigator will follow local or country-specific standard of care.
CetuximabDrug
Also called Erbitux
Cetuximab will be administered intravenously prior to irinotecan at an initial dose of 400 mg/m^2 followed by weekly infusions of 250 mg/m^2. Pre-medication at the discretion of the investigator will follow local or country-specific standard of care.
| Study group | Role | What they receive |
|---|---|---|
| Arm A: Dalotuzumab + Irinotecan | Experimental | Participants receive irinotecan intravenously (IV), 180 mg/m^2 once every two weeks + dalotuzumab IV, 10 mg/kg once weekly, during ≥1 42-day treatment cycle(s). Receives: Drug: Dalotuzumab; Drug: Irinotecan |
| Arm B: Cetuximab + Irinotecan | Active comparator | Participants receive cetuximab IV, initial dose of 400 mg/m^2 and then 250 mg/m^2 IV weekly + irinotecan IV, 180 mg/m^2 once every two weeks, during ≥1 42-day treatment cycle(s). Receives: Drug: Irinotecan; Drug: Cetuximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of Progression-free Survival (PFS)
PFS is a measure of the time from randomization to the time of first documented disease progression (assessed by an independent Radiology Review Committee [iRRC]) or participant death, whichever occurs first.
Measured: From randomization (Cycle 1, Day 1) to the first documented disease progression or death due to any cause, whichever occurs first (up to 3 years)
Secondary outcomes (1)
Percentage of Participants With Objective Response Rate (ORR)
ORR is defined as the percentage of participants achieving a complete response (CR) or partial response (PR) during the course of the study using enhanced Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Confirmation of response was not required.
Measured: From randomization (Cycle 1, Day 1) to the first documented disease progression or death due to any cause, whichever occurs first (up to 3 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 May 2012 (estimated)
- Study start6 Jul 2012
- Primary completion9 Dec 2014
- Study completion9 Dec 2014
Why it stopped: This trial was halted prematurely for business reasons and low enrollment.
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 Rectal 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 11 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
- NCT01609231
- Sponsor's protocol ID
- 0646-025
- Other IDs
- 2012-000317-36, MK-0646-025
- Status last verified
- Apr 2020
- First submitted
- 29 May 2012
- Last updated
- 4 May 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IIA Open Label, Adaptive, Randomized Clinical Trial of Dalotuzumab (MK-0646) Treatment in Combination With Irinotecan Versus Cetuximab and Irinotecan for Patients With Metastatic Rectal Cancers (mRC) Expressing High IGF-1/Low IGF-2 Levels
- ClinicalTrials.gov ID
- NCT01609231
- Acronym / sponsor ID
- 0646-025
- Conditions
- Rectal Neoplasms
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: This trial was halted prematurely for business reasons and low enrollment.
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 6 Jul 2012 (actual)
- Primary completion
- 9 Dec 2014 (actual)
- Study completion
- 9 Dec 2014 (actual)
- First posted
- 31 May 2012 (estimated)
- Results
- Posted 4 May 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this adaptive trial is to compare the progression-free survival of participants with metastatic rectal carcinoma when treated with intravenous (IV) dalotuzumab (MK-0646) + irinotecan therapy relative to participants treated with IV cetuximab + irinotecan. The primary hypothesis is that administration of dalotuzumab in combination with irinotecan to participants with wild-type KRAS metastatic rectal carcinoma with high insulin growth factor (IGF)-1/low IGF-2 expression levels improves progression-free survival compared to patients treated with cetuximab in combination with irinotecan.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A: Dalotuzumab + Irinotecan | Experimental | Drug: Dalotuzumab, Drug: IrinotecanParticipants receive irinotecan intravenously (IV), 180 mg/m^2 once every two weeks + dalotuzumab IV, 10 mg/kg once weekly, during ≥1 42-day treatment cycle(s). |
| Arm B: Cetuximab + Irinotecan | Active comparator | Drug: Irinotecan, Drug: CetuximabParticipants receive cetuximab IV, initial dose of 400 mg/m^2 and then 250 mg/m^2 IV weekly + irinotecan IV, 180 mg/m^2 once every two weeks, during ≥1 42-day treatment cycle(s). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Has metastatic colorectal cancer with primary tumor originating from the rectum
- Has an available archival (recent or remote) tumor, or newly obtained formalin-fixed tissue available for analysis for biomarker studies
- Has at least one measurable lesion greater than or equal to 10 mm
- Disease has progressed after treatment with both irinotecan- and oxaliplatin-containing regimens and should have progressed on or within 3 months of completing their last line of therapy
- Has a performance status 0-1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
Key exclusion criteria (13 listed)
- Has poorly-controlled diabetes
- Has received chemotherapy or biological therapy within 2 weeks prior to initial dosing on this study, or whose toxicities from agents administered 2 weeks earlier have not resolved to at least grade 1 or baseline, or who is within 3 weeks from a prior surgery
- Has received radiotherapy within 2 weeks prior to initial dosing on this study, unless the radiotherapy was for management of pain
- Is currently participating or has participated in a study with an investigational compound or device within 30 days or 5 half-lives of the investigational agent, whichever is longer, of initial dosing on this study
- Was unable to complete previous course of irinotecan due to intolerable toxicity, other than discontinuation due to fatigue following prolonged administration (>4 months exposure)
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 |
|---|---|---|
| DalotuzumabAlso: MK-0646Dalotuzumab will be administered intravenously after the completion of irinotecan infusion at a dose of 10 mg/kg once weekly. | Drug | Arm A: Dalotuzumab + Irinotecan |
| IrinotecanAlso: CamptosarIrinotecan 180 mg/m^2 will be administered intravenously once every two weeks either prior to dalotuzumab (Arm A) or after cetuximab (Arm B). Pre-medication at the discretion of the investigator will follow local or country-specific standard of care. | Drug | Arm A: Dalotuzumab + Irinotecan, Arm B: Cetuximab + Irinotecan |
| CetuximabAlso: ErbituxCetuximab will be administered intravenously prior to irinotecan at an initial dose of 400 mg/m^2 followed by weekly infusions of 250 mg/m^2. Pre-medication at the discretion of the investigator will follow local or country-specific standard of care. | Drug | Arm B: Cetuximab + Irinotecan |
Primary outcome
Assessment of Progression-free Survival (PFS)
Time frame: From randomization (Cycle 1, Day 1) to the first documented disease progression or death due to any cause, whichever occurs first (up to 3 years)
PFS is a measure of the time from randomization to the time of first documented disease progression (assessed by an independent Radiology Review Committee [iRRC]) or participant death, whichever occurs first.
1 secondary outcome
Percentage of Participants With Objective Response Rate (ORR)
Time frame: From randomization (Cycle 1, Day 1) to the first documented disease progression or death due to any cause, whichever occurs first (up to 3 years)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 May 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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 2 study testing Dalotuzumab, Irinotecan and Cetuximab in people with Rectal 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 5 inclusion and 13 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 4 May 2020. 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 phase mean?
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 4 May 2020). 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?
Assessment of Progression-free Survival (PFS) (time frame: From randomization (Cycle 1, Day 1) to the first documented disease progression or death due to any cause, whichever occurs first (up to 3 years)). 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 4 May 2020.