Gastric AdenocarcinomaPhase 2NCT03196232
Epacadostat and Pembrolizumab in Treating Patients With Metastatic or Unresectable Gastroesophageal Junction or Gastric Cancer
A Phase 2 study testing Epacadostat and Pembrolizumab in people with Gastric Adenocarcinoma and Gastroesophageal Junction Adenocarcinoma, run by George Albert Fisher at 1 site in United States.
Trial summary
This phase 2 trial evaluates the benefit of epacadostat plus pembrolizumab in combination to treat patients with gastroesophageal junction or gastric cancer that has spread to other parts of the body and cannot be removed by surgery. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gastric Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma, Recurrent Esophageal Carcinoma
- What is being tested?
- Epacadostat and Pembrolizumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Sep 2017to 29 May 2018
- 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
- ≥ 18 years of age on day of consent
- Histologically-or cytologically-confirmed adenocarcinoma of the distal esophagus [within 5 centimeters of the gastroesophageal junction (GEJ)], gastroesophageal junction or stomach, including HER2+ disease
- Metastatic or unresectable disease, including those with HER2+ disease
- Progressed on at least 1 line of prior therapy for metastatic disease, or intolerant to that therapy if not progressed
- If HER2+ disease, should have received prior trastuzumab
- Life expectancy ≥ 12 weeks
Show all 16Show fewer
- Eastern Cooperative Oncology (ECOG) Performance Status 0 or 1
- Measurable disease per RECIST v1.1, assessed within 4 weeks prior to study entry
- Tumor deemed amenable to biopsy by core for metastatic site or endoscopic biopsy for primary tumor (for both before and on-treatment biopsies)
- Able to swallow pills
- Female subject of childbearing potential should have a negative urine or serum pregnancy within 3 days 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 must be willing to use an adequate method of contraception starting with the date of consent through 120 days after the last dose of study medication. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject
- Male subjects of childbearing potential must agree to use an adequate method of contraception starting with the date of consent through 120 days after the last dose of study therapy. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject
- Prior authorization by Merck in order to enroll in this study is required if previously treated on any Merck-sponsored pembrolizumab-containing gastric cancer pivotal trial
- Willing to undergo 2 biopsies (before and on-treatment), provided the procedure is not deemed high-risk and is clinically feasible
- Willing and able to provide written informed consent/assent
Who cannot join
- Known additional malignancy that has progressed 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
- Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. EXCEPTION: 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 study 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 study treatment; this exception does not include carcinomatous meningitis which is excluded regardless of clinical stability. Patients with prior CNS metastases treated with prior radiation therapy (RT) will also need ALL of the following:
- 2 months off RT before starting study or 4 weeks following radiation therapy (XRT) if magnetic resonance imaging (MRI) is stable and the patient is off steroids
- Baseline MRI with no edema
- Stable for at least 8 weeks
- 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 study medication
Show all 29Show fewer
- Use of systemic corticosteroids
- Currently, or within 4 weeks of the first planned dose of treatment, receiving an investigational agent and using an investigational device
- Prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1, or anyone has not recovered from adverse events (ie, to baseline or ≤ grade 1) due to agents administered more than 4 weeks earlier (EXCEPTION: denosumab for bone metastases is allowed)
- Prior chemotherapy; targeted small molecule therapy; or radiation therapy within 2 weeks prior to study day 1 or who has not recovered from adverse events (ie, to baseline or ≤ grade 1) due to a previously administered agent (EXCEPTION: ≤ grade 2 neuropathy). Recovery from major surgery must be considered adequate prior to starting therapy.
- Prior therapy with indoleamine-pyrrole 2,3-dioxygenase (IDO)-inhibitors
- Prior therapy with monoamine oxidase inhibitors within 21 days before screening
- Presence of a gastrointestinal condition that may affect drug absorption
- Active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease-modifying agents; corticosteroids; or immunosuppressive drugs). EXCEPTION: replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc) is not considered systemic treatment
- Known hypersensitivity to pembrolizumab and/or epacadostat or any of their excipients
- Known allergy or reaction to any component of either study drug or formulation components
- Received a live vaccine, including live attenuated vaccines (eg, Flu-Mist), within 30 days of planned start of study therapy. EXCEPTION: inactivated flu vaccines such as seasonal influenza vaccines for injection are allowed
- Known active hepatitis B (eg, hepatitis B surface antigen [HBsAg] reactive)
- Known active hepatitis C (eg, hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] detected)
- Known history of active tuberculosis (Bacillus tuberculosis)
- Known history of human immunodeficiency virus (HIV) (HIV 1-2 antibodies)
- Known history of, or any evidence of active, non-infectious pneumonitis
- History of serotonin syndrome after receiving 1 or more serotonergic drugs
- Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study
- History or presence of an abnormal electrocardiogram (ECG) which, in the investigator's opinion, is clinically significant
- Corrected QT Fredericia's formula (QTcF) ≥ 480 ms or presence of a left bundle branch block (LBBB); if the QRS duration > 120ms, the JTc can be used in place of the QTcF; the JTc must be < 340 ms
- Active infection requiring systemic therapy
- Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with pre-screening or screening visit through 120 days after the last dose of study treatment
- History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
Trial locations and contacts
1 site in 1 country.
United States1 site
Stanford University, School of Medicine
Palo Alto, California, 94304
About this study
Official title: Phase 2 Study of Epacadostat (INCB024360) With Pembrolizumab (MK3475) in Metastatic or Unresectable Gastroesophageal Junction and Gastric Adenocarcinoma Requiring Paired Biopsies
This phase 2 trial evaluates the benefit of epacadostat plus pembrolizumab in combination to treat patients with gastroesophageal junction or gastric cancer that has spread to other parts of the body and cannot be removed by surgery. Epacadostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as pembrolizumab, may block tumor growth in different ways by targeting certain cells. Giving epacadostat and pembrolizumab may work better in treating patients with gastroesophageal junction or gastric cancer.
Read the detailed description
Patients receive epacadostat orally (PO) twice daily (BID) on Days 1 to 21 and pembrolizumab intravenously (IV) over 30 minutes on Day 1. Courses repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days, every 9 weeks for 18 months, and then every 12 weeks thereafter.
PRIMARY OBJECTIVES:
Assess 6-month progression free survival (PFS).
SECONDARY OBJECTIVES:
- To evaluate objective response rate (RR) by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 and immune-related response criteria (irRC).
- Evaluate overall survival (OS).
- Assess the safety and tolerability of epacadostat in combination with pembrolizumab by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03.
TERTIARY OBJECTIVES:
- Determine the responder rate defined as the proportion of subjects with an increased ratio of CD8+ to Treg cells in on-treatment compared with pre-treatment biopsies.
- Identify putative immunologic biomarkers of tumor response.
- Conditions
- Gastric Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma, Recurrent Esophageal Carcinoma, Recurrent Gastric Carcinoma, Stage IV Esophageal Cancer AJCC v7, Stage IV Gastric Cancer AJCC v7
- Being tested
- Epacadostat, Pembrolizumab
- Medical subject headings
- Esophageal Neoplasms, Stomach Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EpacadostatDrug
Also called INCB 024360, INCB024360
Given PO
PembrolizumabDrug
Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Treatment (epacadostat, pembrolizumab) | Experimental | Participants receive oral epacadostat BID on Days 1 to 21 and pembrolizumab IV over 30 minutes on Day 1, with cycles repeating every 21 days for up to 24 months, in the absence of disease progression or unacceptable toxicity. Receives: Drug: Epacadostat; Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival (PFS)
Progression-free survival (PFS) was assessed as the number of participants remaining alive without progression 6 months after beginning treatment. The outcome is reported as a number without dispersion.
Measured: 6 months
Secondary outcomes (5)
Response Rate
Therapeutic response was assessed per the Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). Criteria are:
- Complete Response (CR) = Disappearance of all target lesions
- Partial Response (PR) = ≥ 30% decrease in the sum of the longest diameter of target lesions
- Overall Response (OR) = CR + PR
- Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions
- Stable disease (SD) = Small changes that do not meet any of the above criteria
The outcome is reported as the number of participants with a documented clinical response (ie, either PR or CR) at 6 months after initiation of treatment.
Measured: Up to 6 months
Overall Survival
Overall survival (OS) was assessed as the number of participants remaining alive 6 months after beginning treatment. The outcome is reported as a number without dispersion.
Measured: 6 months
Number of Adverse Events
Participants were monitored for adverse events. The outcome is reported as the overall number of adverse events of any grade, a number without dispersion.
Measured: Up to 6 months
Number of Adverse Events ≥ Grade 3
Adverse events were assessed per the Common Terminology Criteria for Adverse Events v4.03. The outcome is reported as the number of adverse events ≥ Grade 3, a number without dispersion.
Measured: Up to 6 months
Treatment Delay or Reduction
The assessment for clinical value of the treatment combination included treatment delays or reductions, a measure of how well the combination treatment was tolerated. The outcome is reported as the number of participants that experienced a treatment delay, or reduction in treatment dose level, a number without dispersion.
Measured: Up to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2017
- Study start13 Sep 2017
- Primary completion29 May 2018
- Study completion29 May 2018
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 Gastric AdenocarcinomaStudies of the same condition, open and under way.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- George Albert Fisher
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor-investigator, George Albert Fisher, Stanford University
- Investigators
- George A Fisher, MD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03196232
- Sponsor's protocol ID
- IRB-40823
- Other IDs
- NCI-2017-00895, GI0015
- Status last verified
- Jan 2024
- First submitted
- 20 Jun 2017
- Last updated
- 23 Jan 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Study of Epacadostat (INCB024360) With Pembrolizumab (MK3475) in Metastatic or Unresectable Gastroesophageal Junction and Gastric Adenocarcinoma Requiring Paired Biopsies
- ClinicalTrials.gov ID
- NCT03196232
- Acronym / sponsor ID
- IRB-40823
- Conditions
- Gastric Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma, Recurrent Esophageal Carcinoma, Recurrent Gastric Carcinoma, Stage IV Esophageal Cancer AJCC v7, Stage IV Gastric Cancer AJCC v7
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3 participants (actual)
- Lead sponsor
- George Albert FisherUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 13 Sep 2017 (actual)
- Primary completion
- 29 May 2018 (actual)
- Study completion
- 29 May 2018 (actual)
- First posted
- 22 Jun 2017 (actual)
- Results
- Posted 22 Jun 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase 2 trial evaluates the benefit of epacadostat plus pembrolizumab in combination to treat patients with gastroesophageal junction or gastric cancer that has spread to other parts of the body and cannot be removed by surgery. Epacadostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as pembrolizumab, may block tumor growth in different ways by targeting certain cells. Giving epacadostat and pembrolizumab may work better in treating patients with gastroesophageal junction or gastric cancer.
Detailed description
Patients receive epacadostat orally (PO) twice daily (BID) on Days 1 to 21 and pembrolizumab intravenously (IV) over 30 minutes on Day 1. Courses repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days, every 9 weeks for 18 months, and then every 12 weeks thereafter.
PRIMARY OBJECTIVES:
Assess 6-month progression free survival (PFS).
SECONDARY OBJECTIVES:
- To evaluate objective response rate (RR) by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 and immune-related response criteria (irRC).
- Evaluate overall survival (OS).
- Assess the safety and tolerability of epacadostat in combination with pembrolizumab by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03.
TERTIARY OBJECTIVES:
- Determine the responder rate defined as the proportion of subjects with an increased ratio of CD8+ to Treg cells in on-treatment compared with pre-treatment biopsies.
- Identify putative immunologic biomarkers of tumor response.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (epacadostat, pembrolizumab) | Experimental | Drug: Epacadostat, Drug: PembrolizumabParticipants receive oral epacadostat BID on Days 1 to 21 and pembrolizumab IV over 30 minutes on Day 1, with cycles repeating every 21 days for up to 24 months, in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- ≥ 18 years of age on day of consent
- Histologically-or cytologically-confirmed adenocarcinoma of the distal esophagus [within 5 centimeters of the gastroesophageal junction (GEJ)], gastroesophageal junction or stomach, including HER2+ disease
- Metastatic or unresectable disease, including those with HER2+ disease
- Progressed on at least 1 line of prior therapy for metastatic disease, or intolerant to that therapy if not progressed
- If HER2+ disease, should have received prior trastuzumab
Key exclusion criteria (29 listed)
- Known additional malignancy that has progressed 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
- Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. EXCEPTION: 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 study 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 study treatment; this exception does not include carcinomatous meningitis which is excluded regardless of clinical stability. Patients with prior CNS metastases treated with prior radiation therapy (RT) will also need ALL of the following:
- 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 study medication
- Use of systemic corticosteroids
- Currently, or within 4 weeks of the first planned dose of treatment, receiving an investigational agent and using an investigational device
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 |
|---|---|---|
| EpacadostatAlso: INCB 024360, INCB024360Given PO | Drug | Treatment (epacadostat, pembrolizumab) |
| PembrolizumabAlso: Keytruda, Lambrolizumab, MK-3475, SCH 900475Given IV | Drug | Treatment (epacadostat, pembrolizumab) |
Primary outcome
Progression-free Survival (PFS)
Time frame: 6 months
Progression-free survival (PFS) was assessed as the number of participants remaining alive without progression 6 months after beginning treatment. The outcome is reported as a number without dispersion.
5 secondary outcomes
Response Rate
Time frame: Up to 6 months
Overall Survival
Time frame: 6 months
Number of Adverse Events
Time frame: Up to 6 months
Number of Adverse Events ≥ Grade 3
Time frame: Up to 6 months
Treatment Delay or Reduction
Time frame: Up to 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
George A Fisher, MD principal investigator
Stanford University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Epacadostat and Pembrolizumab in people with Gastric Adenocarcinoma and Gastroesophageal Junction Adenocarcinoma, run by George Albert Fisher 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 16 inclusion and 29 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: finished, as of the sponsor's last update on 23 Jan 2024. 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 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 Jun 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?
Progression-free Survival (PFS) (time frame: 6 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 23 Jan 2024.