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ATM Gene MutationPhase 2NCT03432676

Epacadostat and Pembrolizumab in Treating Participants With Advanced Pancreatic Cancer

A Phase 2 study testing Epacadostat and Pembrolizumab in people with ATM Gene Mutation and Deleterious BRCA1 Gene Mutation, run by M.D. Anderson Cancer Center.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This phase II trial studies how well epacadostat and pembrolizumab work in treating participants with pancreatic cancer that has spread to other places in the body. Epacadostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Epacadostat and Pembrolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
31 Jul 2019to 30 Apr 2021
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

  • Be willing and able to provide written informed consent/assent for the trial
  • Have received at least one prior therapy for metastatic disease
  • Patients with HRD identified by one of the following criteria: a) Tested positive for BRCA 1 or 2 germline deleterious mutation, b) Previously identified genetic aberrations that are associated with HRD (e.g., somatic BRCA mutation, PALB2, Fanconi anemia gene or RAD51 mutations), c) Patients with somatic ATM loss as identifiable with immunohistochemistry or with ATM mutation, d) Pancreatic ductal adenocarcinoma (PDAC) patients with family history of 2 or more first-degree relatives with BRCA-associated cancers (stomach, breast, ovary) or 1 or more first-degree relative with PDAC
  • Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or at least one site of disease must be uni-dimensionally measurable as per RECIST 1.1. All radiology studies must be performed within 28 days prior to registration
  • Patients must have an archival sample of tumor or metastatic site core biopsy to be eligible
  • Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
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  • Within 10 days of treatment initiation: Absolute neutrophil count (ANC) >= 1.5 x 109/L
  • Within 10 days of treatment initiation: platelet count >= 100 x 109/L
  • Within 10 days of treatment initiation: hemoglobin >= 9 g/dl without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment)
  • Within 10 days of treatment initiation: If serum creatinine concentration >= 1.5 x upper limit of normal (ULN), then estimated creatinine clearance must be >= 60 mL/min for subject with creatinine levels > 1.5 x institutional ULN
  • Within 10 days of treatment initiation: total bilirubin =< 1.5 x ULN (3 x ULN if a exists a history of Gilbert syndrome) or direct bilirubin >= ULN for subjects with total bilirubin levels > 1.5 ULN
  • Within 10 days of treatment initiation: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN
  • Within 10 days of treatment initiation: albumin >= 3 mg/dL. Creatinine clearance should be calculated per institutional standard
  • 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 must be willing to use an adequate method of contraception, for the course of the study 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. Contraception, starting with the first dose of study therapy 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

Who cannot join

  • Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
  • For screening electrocardiographs (ECGs), exclude patients with a Fridericia's corrected QT interval (QTcF) > 480 ms, or JTc > 340 ms for those with an intraventricular conduction delay. If the screening ECG has a QTcF > 480 ms, eligibility can be confirmed if the average of 3 ECGs done 5 minutes apart have an average QTcF < 480 ms
  • 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
  • Has a known history of active TB (Bacillus tuberculosis)
  • Hypersensitivity to pembrolizumab or epacadostat or any of their excipients
  • Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
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  • 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., =< grade 1 or at baseline) from adverse events due to a previously administered agent. Note: Subjects with =< grade 2 neuropathy are an exception to this criterion and may qualify for the study. Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
  • Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
  • 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. This exception does not include carcinomatous meningitis, which is excluded regardless of clinical stability
  • Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
  • Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
  • 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-IDO-1 agent
  • Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
  • Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
  • Has received a live vaccine within 30 days of planned start of study therapy
  • Has ascites that requires frequent paracentesis or a pleural effusion that requires repeated thoracentesis
  • Has arterial vascular involvement
  • Has received monoamine oxidase inhibitors within 21 days prior to starting study
  • Has any history of serotonin syndrome after receiving serotonergic drugs

About this study

Official title: Single-Arm, Phase II Proof of Concept Study of IDO-1 Inhibitor Epacadostat in Combination With Pembrolizumab in Advanced Pancreatic Cancer With Chromosomal Instability/Homologous Recombination Repair Deficiency (HRD)

This phase II trial studies how well epacadostat and pembrolizumab work in treating participants with pancreatic cancer that has spread to other places in the body. Epacadostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving epacadostat and pembrolizumab may work better in treating participants with pancreatic cancer.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the efficacy of epacadostat in combination with pembrolizumab as determined by the best overall response rate in previously treated patients with advanced pancreatic adenocarcinoma with homologous recombination repair deficiency (HRD) aberrations.

SECONDARY OBJECTIVES:

  1. To further determine the efficacy of epacadostat in combination with pembrolizumab in previously treated patients with advanced pancreatic adenocarcinoma with HRD aberrations.

II. To assess the safety and tolerability of epacadostat in combination with pembrolizumab in previously treated patients with advanced pancreatic adenocarcinoma with HRD aberrations.

EXPLORATORY OBJECTIVES:

  1. To identify predictive, mechanistic, and/or surrogate biomarkers of clinical efficacy of epacadostat in combination with pembrolizumab in previously treated patients with advanced pancreatic adenocarcinoma with HRD aberrations utilizing exploratory studies investigating the patients tumor and immune system response including: flow cytometry of fresh peripheral blood mononuclear cell (PBMC), PDL-1.

OUTLINE:

Participants receive pembrolizumab intravenously (IV) over 30 minutes on day 1 and epacadostat orally (PO) twice daily (BID) on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unaccepted toxicity.

After completion of study treatment, participants are followed up at 30 days, every 8 weeks for 3 years, and then every 12 weeks thereafter.

Being tested
Epacadostat, Pembrolizumab
Medical subject headings
Pancreatic 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

  • PembrolizumabBiological

    Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475

    Given IV

Study groups in NCT03432676
Study groupRoleWhat they receive
Treatment (pembrolizumab, epacadostat)ExperimentalParticipants receive pembrolizumab IV over 30 minutes on day 1 and epacadostat PO BID on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unaccepted toxicity.
Receives: Drug: Epacadostat; Biological: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Best objective response rate

    The objective response rate (partial response [PR] + complete response [CR]) and its corresponding exact 1-sided 90% confidence interval (CI) will be estimated.

    Measured: Up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Feb 2018
  2. Study start31 Jul 2019 (estimated)
  3. Primary completion30 Apr 2020 (estimated)
  4. Study completion30 Apr 2021 (estimated)

Why it stopped: Incyte (supporter of the study) is no longer going to support the study.

Resources

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
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03432676
Sponsor's protocol ID
2016-0893
Other IDs
NCI-2018-00912, 2016-0893, P30CA016672
Status last verified
May 2019
First submitted
6 Feb 2018
Last updated
30 May 2019
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Epacadostat and Pembrolizumab in people with ATM Gene Mutation and Deleterious BRCA1 Gene Mutation, run by M.D. Anderson Cancer Center.

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 23 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 30 May 2019. 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?

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?

Best objective response rate (time frame: Up to 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03432676.

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 30 May 2019.

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