Advanced GI CancerPhase 1MK-3475 GINCT02268825
Phase I Study MK-3475 With Chemotherapy in Patients With Advanced GI Cancers
A Phase 1 study testing MK-3475 in people with Advanced GI Cancer, run by University of Utah at 1 site in United States.
Trial summary
This is a Phase I dose escalation trial to assess MTD of MK-3475 in combination with mFOLFOX6 followed by a safety expansion open label, nonrandomized trial with MK-3475 at MTD in combination with mFOLFOX6 and supplemental celecoxib in 4 cohorts of advanced/metastatic GI malignancies (pancreatic, gastro esophageal… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced GI Cancer
- What is being tested?
- MK-3475
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Jan 2015to 26 Jun 2017
- Phase
- Phase 1
- 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
- Phase I: Patients with any locally advanced or metastatic gastrointestinal malignancy which mFOLFOX6 is indicated for treatment
- Safety expansion: Patients with one of the following locally advanced unresectable or metastatic pathologically confirmed diagnosis: Colorectal Carcinoma and Appendiceal Adenocarcinoma, Gastro-Esophageal -Carcinoma Note: esophageal squamous cell carcinoma is exclusionary, Biliary -Tract Carcinoma Note: Hepatocellular carcinoma is excluded, Pancreatic Carcinoma
- Patients must be willing to provide and have available formalin fixed paraffin embedded tissue sample from archival tissue or newly obtained core or excisional biopsy of a tumor lesion for central analysis. Note: Fine Needle Aspiration's (FNA), frozen samples, plastic embedded samples, cell blocks, clots, bone, bone marrow, or cytologic specimens are exclusionary
- Patients must have measurable disease based on irRECIST (Safety expansion only)
- Patients must be 18 years of age on day of signing informed consent
- Have a performance status of 0 or 1 on the ECOG Performance Scale
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- Patients must demonstrate adequate organ function as based on screening labs performed within 14 days of treatment initiation
- Patients are allowed to have received prior treatment with mFOLFOX6. If patients are currently receiving treatment with mFOLFOX6, the subject must have documented disease progression. Patients must also be able to tolerate standard mFOLFOX6. Reduced dosing of mFOLFOX6 at enrollment is exclusionary.
- Patients must be able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines
- Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
- Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for greater than 1 year
- Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy
Who cannot join
- Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Note: Dexamethasone prior to treatment on day 1 of each treatment cycle is allowed
- Subjects with greater than or equal to Grade 2 neuropathy
- Has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., greater than or equal to Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
- Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., less than or equal to Grade 1 or at baseline) from adverse events due to a previously administered agent. Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
- History of greater than or equal to grade 3 allergic reaction to mFOLFOX6 (patients successfully desensitized to oxaliplatin are eligible or those willing to undergo desensitization during the first two cycles of mFOLFOX6 per institutional guidelines)
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- Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment
- Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators, topical steroids or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study
- Has history of interstitial lung disease or active, non-infectious pneumonitis requiring steroids.
- Has an active infection requiring systemic therapy
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
- Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
- Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). Note: testing not required at baseline unless clinically indicated
- Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected). Note: testing not required at baseline for unless clinically indicated
- Has received a live vaccine within 30 days prior to the first dose of trial treatment
- Patients are ineligible if they plan on regular use of NSAIDs at any dose more than 2 times per week (on average) or aspirin at more than 325 mg at least three times per week, on average. Low-dose aspirin not exceeding 100mg/day is permitted. Patients who agree to stop regular NSAIDS or higher dose aspirin are eligible and no wash out period is required.
- The patient has significant bleeding disorders or vasculitis. History of significant (in the opinion of the investigator) upper gastrointestinal ulceration, upper gastrointestinal bleeding, or upper gastrointestinal perforation within the past 3 years. Patients with a history of ulceration, bleeding or perforation in the lower bowel are not excluded.
- Prior allergic reaction or hypersensitivity to sulfonamides (may be allowed per investigator discretion based on patient history), celecoxib or NSAIDs.
- Cardiac risk factors including: 1) Uncontrolled high blood pressure (systolic blood pressure greater than 150); 2) Unstable angina; 3) History of documented myocardial infarction or cerebrovascular accident; 4 New York Heart Association class III or IV heart failure.
Trial locations and contacts
1 site in 1 country.
United States1 site
Huntsman Cancer Institute
Salt Lake City, Utah, 84112
About this study
Official title: A Phase I Study of MK-3475 in Combination With Chemotherapy and Supplemental Celecoxib in Patients With Advanced GI Cancers (Colorectal/Appendiceal Adenocarcinoma, Gastroesophageal, Pancreatic and Biliary)
This is a Phase I dose escalation trial to assess MTD of MK-3475 in combination with mFOLFOX6 followed by a safety expansion open label, nonrandomized trial with MK-3475 at MTD in combination with mFOLFOX6 and supplemental celecoxib in 4 cohorts of advanced/metastatic GI malignancies (pancreatic, gastro esophageal, colorectal/appendiceal adenocarcinoma and biliary carcinoma) to assess response rate, clinical benefit rate, progression free survival and overall survival. The safety expansion cohort will assess the effect of the addition of celecoxib to patients that do not respond to combination MK-3475/mFOLFOX treatment.
- Conditions
- Advanced GI Cancer
- Being tested
- MK-3475
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MK-3475Drug
MK-3475 in combination with mFOLFOX6 in a 14 day cycle
Phase 1 and safety expansion Phased Regimen mFOLFOX6 Administered Day 1 of each cycle Leucovorin 400 mg/m2 IV 5-FU 400 mg/m2 IV bolus followed by 2400 mg/m2 IV over 46 hrs Oxaliplatin (Eloxatin) 85 mg/m2 IV
MK-3475 IV to be administered before mFOLFOX6 starting with Cycle 3 (after 28 days of chemotherapy alone); day 1 of each cycle (q 2 weeks)
Phase 1: 2 dose levels of MK-3475 Level -1: 50mg IV q 2 weeks Level 1: 75mg IV q 2 weeks Level 2: 200mg IV q 2 weeks
Safety Expansion: MK-3475 at highest tolerated dose
| Study group | Role | What they receive |
|---|---|---|
| MK-3475 treatment arm, all patients | Experimental | Not described Receives: Drug: MK-3475 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of combination mFOLFOX and MK-3475
Routine safety and tolerability will be evaluated from the results of reported signs and symptoms, scheduled physical examinations, vital sign measurements, and clinical laboratory test results. More frequent safety evaluations may be performed if clinically indicated or at the discretion of the investigator.
Measured: Patient safety will be evaluated throughout the treatment period (treatment with MK-3475 and FOLFOX) which is expected to last 4-6 months for each patient.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2014 (estimated)
- Study start23 Jan 2015
- Primary completion25 Jan 2017
- Study completion26 Jun 2017
Why it stopped: Merck requested to change MK-3475 dosing schedule; PI decided to close instead
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced GI CancerStudies of the same condition, open and under way.
- More trials run by University of UtahThe 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Utah
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02268825
- Sponsor's protocol ID
- HCI76239
- Acronym
- MK-3475 GI
- Status last verified
- Nov 2018
- First submitted
- 15 Oct 2014
- Last updated
- 13 Nov 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of MK-3475 in Combination With Chemotherapy and Supplemental Celecoxib in Patients With Advanced GI Cancers (Colorectal/Appendiceal Adenocarcinoma, Gastroesophageal, Pancreatic and Biliary)
- ClinicalTrials.gov ID
- NCT02268825
- Acronym / sponsor ID
- MK-3475 GI / HCI76239
- Conditions
- Advanced GI Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Merck requested to change MK-3475 dosing schedule; PI decided to close instead
- Enrolment
- 39 participants (actual)
- Lead sponsor
- University of UtahUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 23 Jan 2015 (actual)
- Primary completion
- 25 Jan 2017 (actual)
- Study completion
- 26 Jun 2017 (actual)
- First posted
- 20 Oct 2014 (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.
This is a Phase I dose escalation trial to assess MTD of MK-3475 in combination with mFOLFOX6 followed by a safety expansion open label, nonrandomized trial with MK-3475 at MTD in combination with mFOLFOX6 and supplemental celecoxib in 4 cohorts of advanced/metastatic GI malignancies (pancreatic, gastro esophageal, colorectal/appendiceal adenocarcinoma and biliary carcinoma) to assess response rate, clinical benefit rate, progression free survival and overall survival. The safety expansion cohort will assess the effect of the addition of celecoxib to patients that do not respond to combination MK-3475/mFOLFOX treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| MK-3475 treatment arm, all patients | Experimental | Drug: MK-3475 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Phase I: Patients with any locally advanced or metastatic gastrointestinal malignancy which mFOLFOX6 is indicated for treatment
- Safety expansion: Patients with one of the following locally advanced unresectable or metastatic pathologically confirmed diagnosis: Colorectal Carcinoma and Appendiceal Adenocarcinoma, Gastro-Esophageal -Carcinoma Note: esophageal squamous cell carcinoma is exclusionary, Biliary -Tract Carcinoma Note: Hepatocellular carcinoma is excluded, Pancreatic Carcinoma
- Patients must be willing to provide and have available formalin fixed paraffin embedded tissue sample from archival tissue or newly obtained core or excisional biopsy of a tumor lesion for central analysis. Note: Fine Needle Aspiration's (FNA), frozen samples, plastic embedded samples, cell blocks, clots, bone, bone marrow, or cytologic specimens are exclusionary
- Patients must have measurable disease based on irRECIST (Safety expansion only)
- Patients must be 18 years of age on day of signing informed consent
Key exclusion criteria (22 listed)
- Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Note: Dexamethasone prior to treatment on day 1 of each treatment cycle is allowed
- Subjects with greater than or equal to Grade 2 neuropathy
- Has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., greater than or equal to Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
- Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., less than or equal to Grade 1 or at baseline) from adverse events due to a previously administered agent. Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
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-3475MK-3475 in combination with mFOLFOX6 in a 14 day cycle Phase 1 and safety expansion Phased Regimen mFOLFOX6 Administered Day 1 of each cycle Leucovorin 400 mg/m2 IV 5-FU 400 mg/m2 IV bolus followed by 2400 mg/m2 IV over 46 hrs Oxaliplatin (Eloxatin) 85 mg/m2 IV MK-3475 IV to be administered before mFOLFOX6 starting with Cycle 3 (after 28 days of chemotherapy alone); day 1 of each cycle (q 2 weeks) Phase 1: 2 dose levels of MK-3475 Level -1: 50mg IV q 2 weeks Level 1: 75mg IV q 2 weeks Level 2: 200mg IV q 2 weeks Safety Expansion: MK-3475 at highest tolerated dose | Drug | MK-3475 treatment arm, all patients |
Primary outcome
Safety of combination mFOLFOX and MK-3475
Time frame: Patient safety will be evaluated throughout the treatment period (treatment with MK-3475 and FOLFOX) which is expected to last 4-6 months for each patient.
Routine safety and tolerability will be evaluated from the results of reported signs and symptoms, scheduled physical examinations, vital sign measurements, and clinical laboratory test results. More frequent safety evaluations may be performed if clinically indicated or at the discretion of the investigator.
Results and safety
The study was stopped early (reason given: Merck requested to change MK-3475 dosing schedule; PI decided to close instead). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Nov 2018.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MK-3475 in people with Advanced GI Cancer, run by University of Utah at 1 site in United States.
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 12 inclusion and 22 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 13 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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 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.
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 stopped early (reason given: Merck requested to change MK-3475 dosing schedule; PI decided to close instead). Results are not available in the source record.
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?
Safety of combination mFOLFOX and MK-3475 (time frame: Patient safety will be evaluated throughout the treatment period (treatment with MK-3475 and FOLFOX) which is expected to last 4-6 months for each patient.). 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 13 Nov 2018; AzTrials last refreshed its copy on 6 Nov 2026.