Metastatic Colorectal CancerPhase 2NCT01175291
FOLFOX/Bevacizumab +/- MK-0646 in Metastatic Colorectal Cancer
A Phase 2 study testing MK-0646 in people with Metastatic Colorectal Cancer, run by H. Lee Moffitt Cancer Center and Research Institute.
Trial summary
The purpose is to study the efficacy (effectiveness) of a new drug, MK-0646, in metastatic colorectal cancer. MK-0646 is an investigational or experimental anti-cancer agent that has not yet been approved by the U.S. Food and Drug Administration (FDA) for use in metastatic colorectal cancer or any other disease. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Colorectal Cancer
- What is being tested?
- MK-0646
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Sep 2010to Jul 2012
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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
- Metastatic colorectal adenocarcinoma.
- Measurable disease by RECIST criteria.
- Adequate hepatic function: total bilirubin ≤2.0 x upper limits of normal (ULN); Aspartate Amino Transferase (AST)/Alanine Amino Transferase (ALT) ≤3.0X upper limits of normal (or ≤5X upper limits of normal if attributable to liver metastases).
- Adequate renal function: serum creatinine ≤2.0 mg/dl.
- Adequate bone marrow function: absolute neutrophil count ≥1,500/mm3; platelets ≥ 100,000/mm3.
- Prothrombin time (PT) and activated partial thromboplastin time (aPTT) levels ≤1.5 upper limit of normal (unless patients receiving coumadin anticoagulation in which case a stable international normalized ratio (INR) of 2-3 is required).
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- Age ≥ 18 years.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
- Life expectancy ≥ 12 weeks.
- Negative pregnancy test.
- Ability to sign informed consent.
Who cannot join
- Prior systemic chemotherapy for metastatic colorectal cancer
- Prior oxaliplatin in the adjuvant setting within 12 months
- Uncontrolled central nervous system metastases or carcinomatous meningitis.
- Myocardial infarction in the past 6 months.
- Major surgery within 8 weeks prior to enrollment.
- Uncontrolled serious medical or psychiatric illness.
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- Inadequately controlled hypertension (defined as systolic blood pressure >160mmHg, or diastolic blood pressure > 100mmHg).
- Pregnant or lactating women. Both men and women of childbearing potential must be advised of the importance of using effective birth control measures during the course of study.
- Prior experimental therapy targeting the IGF-1 pathway
- Concurrent malignancy (with the exception of squamous or basal cell skin carcinoma)
- Planned surgical metastasectomy
- Patient has known hypersensitivity to components of treatment, their analogs, or drugs of similar chemical or biologic composition
About this study
Official title: Randomized, Double Blind Phase II Study of FOLFOX/Bevacizumab Combined With MK-0646 Versus FOLFOX/Bevacizumab Combined With Placebo in First-Line Treatment of Metastatic Colorectal Cancer
The purpose is to study the efficacy (effectiveness) of a new drug, MK-0646, in metastatic colorectal cancer. MK-0646 is an investigational or experimental anti-cancer agent that has not yet been approved by the U.S. Food and Drug Administration (FDA) for use in metastatic colorectal cancer or any other disease.
This study will assess whether adding MK-0646 to an FDA-approved standard of care chemotherapy improves participants' duration of progression-free survival. MK-0646 is believed to inhibit the receptor of a protein called IGF-1 (Insulin-like Growth Factor) which is thought to contribute to cancer development and growth. However, there is no guarantee that MK-0646 will slow cancer development and growth.
Read more
Other purposes of this study include:
- looking at the safety and tolerability of MK-0646
- comparing MK-0646 + standard of care chemotherapy with placebo + standard of care chemotherapy (placebo is a substance that looks like an active drug but has no active ingredient) The standard of care chemotherapy in this study is called FOLFOX 7. FOLFOX 7 includes the drugs oxaliplatin with leucovorin, 5-Fluorouracil (5-FU), and bevacizumab.
Read the detailed description
Participants randomized to ARM A will receive modified FOLFOX 7 every other week + MK-0646 every week:
5-FU 400 mg/m2 by intravenous infusion over 2-5 minutes Leucovorin 400 mg/m2 by intravenous infusion over 2 hours Oxaliplatin 85 mg/m2 by intravenous infusion over 2 hours (with leucovorin) Bevacizumab 5 mg/kg by intravenous infusion over 30 minutes (+/- 15 minutes) following infusions may be given over 10 minutes (+/- 10 minutes) if the first infusion is tolerated well.
5-FU 2400 mg/m2 by continuous intravenous infusion over 46 hours (may be delivered via automated outpatient pump) Antiemetics (drugs that prevent nausea and vomiting): 5-HT3 receptor antagonist (e.g. ondansetron) and dexamethasone are recommended prior to chemotherapy.
MK-0646 10 mg/kg by intravenous infusion over 60 minutes every week (participants larger than 100 kg [220 pounds] will receive their infusions over 120 minutes).
Participants randomized to ARM B will receive modified FOLFOX 7 every other week + placebo every week:
5-FU 400 mg/m2 by intravenous infusion over 2-5 minutes Leucovorin 400 mg/m2 by intravenous infusion over 2 hours Oxaliplatin 85 mg/m2 by intravenous infusion over 2 hours (with leucovorin) Bevacizumab 5 mg/kg by intravenous infusion over 30 minutes (+/- 15 minutes); following infusions may be given over 10 minutes (+/- 10 minutes) if the first infusion is tolerated well.
5-FU 2400 mg/m2 by continuous intravenous infusion over 46 hours (may be delivered via automated outpatient pump) Antiemetics: 5-HT3 receptor antagonist (e.g. ondansetron) and dexamethasone are recommended prior to chemotherapy Placebo by intravenous infusion over 60 minutes every week (participants larger than 100 kg [220 pounds] will receive their infusions over 120 minutes).
- Conditions
- Metastatic Colorectal Cancer
- Being tested
- MK-0646, Placebo
- Keywords
- colon, rectum, colorectal, metastatic, adenocarcinoma
- Medical subject headings
- Colorectal Neoplasms, Neoplasm Metastasis, Adenocarcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MK-0646Drug
Also called oxaliplatin, leucovorin, 5-FU, Fluorouracil
ARM A will receive FOLFOX 7 (Oxaliplatin with leucovorin + 5-Fluorouracil [5-FU] + Bevacizumab) + MK-0646 (Investigational).
PlaceboDrug
Also called oxaliplatin, leucovorin, 5-FU, 5-Fluorouracil
ARM B will receive FOLFOX 7 (Oxaliplatin with leucovorin + 5-Fluorouracil [5-FU] + Bevacizumab) + placebo: standard of care chemotherapy plus placebo.
| Study group | Role | What they receive |
|---|---|---|
| Arm A - FOLFOX 7 + MK-0646 | Active comparator | Not described Receives: Drug: MK-0646 |
| Arm B - FOLFOX 7 + Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival
To determine whether the administration of MK-0646 with FOLFOX and bevacizumab (experimental arm) improves progression-free survival (PFS) versus FOLFOX and bevacizumab combined with placebo (control arm).
Measured: Average of 12 months
Secondary outcomes (3)
Objective Radiographic Response
To determine whether the objective radiographic response (ORR) is higher in patients treated with FOLFOX and bevacizumab combined with MK-0646 (experimental arm) versus FOLFOX and bevacizumab combined with placebo (control arm).
Measured: Average of 12 months
Overall Survival
To determine whether overall survival (OS) is higher in patients treated with FOLFOX and bevacizumab combined with MK-0646 (experimental arm) versus FOLFOX and bevacizumab combined with placebo (control arm).
Measured: Average of 12 Months
Number of Participants with Adverse Events
To determine the safety and tolerability of MK-0646 combined with FOLFOX and bevacizumab. Safety and tolerability will be assessed according to the NIH/NCI CTC Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.
Measured: Average of 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Aug 2010 (estimated)
- Study startSep 2010
- Primary completionJul 2012 (estimated)
- Study completionJul 2012 (estimated)
Why it stopped: treatment deemed ineffective so accrual was closed
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Colorectal CancerStudies of the same condition, open and under way.
- More trials run by H. Lee Moffitt Cancer Center and Research InstituteThe 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
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01175291
- Sponsor's protocol ID
- MCC-16145
- Status last verified
- Dec 2011
- First submitted
- 2 Aug 2010
- Last updated
- 5 Dec 2011
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Double Blind Phase II Study of FOLFOX/Bevacizumab Combined With MK-0646 Versus FOLFOX/Bevacizumab Combined With Placebo in First-Line Treatment of Metastatic Colorectal Cancer
- ClinicalTrials.gov ID
- NCT01175291
- Acronym / sponsor ID
- MCC-16145
- Conditions
- Metastatic Colorectal Cancer
- Keywords
- colon, rectum, colorectal, metastatic, adenocarcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: treatment deemed ineffective so accrual was closed
- Enrolment
- 0 participants (actual)
- Lead sponsor
- H. Lee Moffitt Cancer Center and Research InstituteUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- Sep 2010
- Primary completion
- Jul 2012 (estimated)
- Study completion
- Jul 2012 (estimated)
- First posted
- 4 Aug 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose is to study the efficacy (effectiveness) of a new drug, MK-0646, in metastatic colorectal cancer. MK-0646 is an investigational or experimental anti-cancer agent that has not yet been approved by the U.S. Food and Drug Administration (FDA) for use in metastatic colorectal cancer or any other disease.
This study will assess whether adding MK-0646 to an FDA-approved standard of care chemotherapy improves participants' duration of progression-free survival. MK-0646 is believed to inhibit the receptor of a protein called IGF-1 (Insulin-like Growth Factor) which is thought to contribute to cancer development and growth. However, there is no guarantee that MK-0646 will slow cancer development and growth.
Other purposes of this study include:
- looking at the safety and tolerability of MK-0646
- comparing MK-0646 + standard of care chemotherapy with placebo + standard of care chemotherapy (placebo is a substance that looks like an active drug but has no active ingredient) The standard of care chemotherapy in this study is called FOLFOX 7. FOLFOX 7 includes the drugs oxaliplatin with leucovorin, 5-Fluorouracil (5-FU), and bevacizumab.
Detailed description
Participants randomized to ARM A will receive modified FOLFOX 7 every other week + MK-0646 every week:
5-FU 400 mg/m2 by intravenous infusion over 2-5 minutes Leucovorin 400 mg/m2 by intravenous infusion over 2 hours Oxaliplatin 85 mg/m2 by intravenous infusion over 2 hours (with leucovorin) Bevacizumab 5 mg/kg by intravenous infusion over 30 minutes (+/- 15 minutes) following infusions may be given over 10 minutes (+/- 10 minutes) if the first infusion is tolerated well.
5-FU 2400 mg/m2 by continuous intravenous infusion over 46 hours (may be delivered via automated outpatient pump) Antiemetics (drugs that prevent nausea and vomiting): 5-HT3 receptor antagonist (e.g. ondansetron) and dexamethasone are recommended prior to chemotherapy.
MK-0646 10 mg/kg by intravenous infusion over 60 minutes every week (participants larger than 100 kg [220 pounds] will receive their infusions over 120 minutes).
Participants randomized to ARM B will receive modified FOLFOX 7 every other week + placebo every week:
5-FU 400 mg/m2 by intravenous infusion over 2-5 minutes Leucovorin 400 mg/m2 by intravenous infusion over 2 hours Oxaliplatin 85 mg/m2 by intravenous infusion over 2 hours (with leucovorin) Bevacizumab 5 mg/kg by intravenous infusion over 30 minutes (+/- 15 minutes); following infusions may be given over 10 minutes (+/- 10 minutes) if the first infusion is tolerated well.
5-FU 2400 mg/m2 by continuous intravenous infusion over 46 hours (may be delivered via automated outpatient pump) Antiemetics: 5-HT3 receptor antagonist (e.g. ondansetron) and dexamethasone are recommended prior to chemotherapy Placebo by intravenous infusion over 60 minutes every week (participants larger than 100 kg [220 pounds] will receive their infusions over 120 minutes).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A - FOLFOX 7 + MK-0646 | Active comparator | Drug: MK-0646 |
| Arm B - FOLFOX 7 + Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Metastatic colorectal adenocarcinoma.
- Measurable disease by RECIST criteria.
- Adequate hepatic function: total bilirubin ≤2.0 x upper limits of normal (ULN); Aspartate Amino Transferase (AST)/Alanine Amino Transferase (ALT) ≤3.0X upper limits of normal (or ≤5X upper limits of normal if attributable to liver metastases).
- Adequate renal function: serum creatinine ≤2.0 mg/dl.
- Adequate bone marrow function: absolute neutrophil count ≥1,500/mm3; platelets ≥ 100,000/mm3.
Key exclusion criteria (12 listed)
- Prior systemic chemotherapy for metastatic colorectal cancer
- Prior oxaliplatin in the adjuvant setting within 12 months
- Uncontrolled central nervous system metastases or carcinomatous meningitis.
- Myocardial infarction in the past 6 months.
- Major surgery within 8 weeks prior to enrollment.
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 |
|---|---|---|
| MK-0646Also: oxaliplatin, leucovorin, 5-FU, FluorouracilARM A will receive FOLFOX 7 (Oxaliplatin with leucovorin + 5-Fluorouracil [5-FU] + Bevacizumab) + MK-0646 (Investigational). | Drug | Arm A - FOLFOX 7 + MK-0646 |
| PlaceboAlso: oxaliplatin, leucovorin, 5-FU, 5-FluorouracilARM B will receive FOLFOX 7 (Oxaliplatin with leucovorin + 5-Fluorouracil [5-FU] + Bevacizumab) + placebo: standard of care chemotherapy plus placebo. | Drug | Arm B - FOLFOX 7 + Placebo |
Primary outcome
Progression Free Survival
Time frame: Average of 12 months
To determine whether the administration of MK-0646 with FOLFOX and bevacizumab (experimental arm) improves progression-free survival (PFS) versus FOLFOX and bevacizumab combined with placebo (control arm).
3 secondary outcomes
Objective Radiographic Response
Time frame: Average of 12 months
Overall Survival
Time frame: Average of 12 Months
Number of Participants with Adverse Events
Time frame: Average of 12 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2011.
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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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing MK-0646 in people with Metastatic Colorectal Cancer, run by H. Lee Moffitt Cancer Center and Research Institute.
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 11 inclusion and 12 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: withdrawn, as of the sponsor's last update on 5 Dec 2011. 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. Some participants in this study may receive a placebo. 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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Progression Free Survival (time frame: Average of 12 months). 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 5 Dec 2011.