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MesotheliomaPhase 1/2NCT03319537

Pevonedistat Alone and in Combination With Chemotherapy in Patients With Mesothelioma

A Phase 1/2 study testing pevonedistat and Pemetrexed and cisplatin in people with Mesothelioma, run by Memorial Sloan Kettering Cancer Center at 8 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The purpose of this study is to test any good and bad effects of activity pevonedistat taken alone, and also to test the safety of pevonedistat in combination with standard chemotherapy, pemetrexed/cisplatin. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Mesothelioma
What is being tested?
pevonedistat and Pemetrexed and cisplatin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
8 sitesUnited States
Study dates
5 Oct 2017to 5 Jun 2023
Phase
Phase 1/2
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

  • Both cohorts:
  • Patients must have a histologically confirmed diagnosis of epithelioid, sarcomatoid, or mixed-type malignant pleural or peritoneal mesothelioma that is not amenable to surgery.
  • Patients must have measurable disease according to the modified RECIST criteria for pleural mesothelioma, or standard RECIST for peritoneal mesothelioma. Patients must have adequate tissue sample available for molecular profiling with MSK-IMPACT (archived tissue block or 15-20 unstained slides). Patients will sign a separate informed document (IRB #12-245) to allow this to be performed.
  • Patients must be at least 18 years of age.
  • Karnofsky performance status ≥ 70%.
  • Adequate renal function: serum creatinine ≤ 1.5 x ULN.
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  • Clinical laboratory values within the following parameters (repeat if more than 7 days before the first dose):
  • °Albumin > 2.7 g/dL
  • Patients must have adequate hepatic function as defined by:
  • AST and ALT ≤ 2.5 x ULN
  • Total bilirubin ≤ upper limit of normal (ULN) except in patients with Gilbert's syndrome. Patients with Gilbert's syndrome may enroll if direct bilirubin ≤1.5 x ULN of the direct bilirubin.
  • Patients must have adequate bone marrow function as defined by:
  • Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
  • Platelets ≥ 100 x 10^9/L
  • Hemoglobin ≥ 9 g/dL.
  • Female patients who
  • Are postmenopausal for at least 1 year before the screening visit, OR
  • Are surgically sterile, OR
  • If they are of childbearing potential:
  • Agree to practice 1 highly effective method and 1 additional effective (barrier) method of contraception, at the same time, from the time of signing the informed consent through 4 months after the last dose of study drug (female and male condoms should not be used together), or
  • Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, postovulation methods] withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception.)
  • Male patients, even if surgically sterilized (i.e., status post vasectomy), who:
  • Agree to practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study drug (female and male condoms should not be used together), or
  • Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, postovulation methods for the female partner] withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception.)
  • Signed informed consent
  • Cohort 1:
  • Patients must have received at least one and no more than four prior systemic therapy regimens. At least one of the regimens must have included pemetrexed and a platinum.
  • Patients must have MM that harbors an NF2 mutation believed to cause functional loss of the NF2 protein as determined by any CLIA lab certified NGS platform or NF2 loss must be documented by CLIA certified IHC.
  • Cohort 2:
  • Patients must not have previously received treatment with chemotherapy for MM.
  • Patients must not have ≥ grade 2 peripheral neuropathy.
  • Patients must not have > grade 2 hearing deficits.

Who cannot join

  • Patients currently receiving radiation therapy, or who have received radiation within 2 weeks from the start of therapy. Patients who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or patients that may require major surgery during the course of the study.
  • Diagnosed or treated for another malignancy within 2 years before randomization or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone resection.
  • Life-threatening illness unrelated to cancer.
  • Patients with uncontrolled coagulopathy or bleeding disorder.
  • Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
  • Known cardiopulmonary disease defined as:
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  • Unstable angina
  • Congestive heart failure (New York Hear Association [NYHA] Class III or IV
  • Myocardial infarction (MI) within 6 months prior to first dose (patients who had ischemic heart disease such as ACS, MI and/or revascularization greater than 6 months before screening and who are without cardiac symptoms may enroll.
  • Cardiomyopathy
  • Clinically significant arrhythmia:
  • Polymorphic ventricular fibrillation or torsade de pointes.
  • Permanent atrial fibrillation [a fib], defined as continuous a fib ≥ 6 months.
  • Persistent a fib, defined as sustained a fib lasting > 7 days and/or requiring cardioversion in the 4 weeks before screening
  • Grade 3 a fib defined as symptomatic and incompletely controlled medically, or controlled with device (e.g. pacemaker), or ablation
  • Patients with paroxysmal a fib or < Gr 3 a fib for period of at least 6 months are permitted to enroll provided that their rate is controlled on a stable regimen.
  • Implantable cardioverter defibrillator
  • Moderate to severe aortic and/or mitral stenosis or other valvulopathy (ongoing)
  • Symptomatic pulmonary hypertension
  • Active infection requiring IV antibiotic, antiviral, or anti-fungal medications within 2 weeks of starting study drug.
  • Known history of HIV seropositivity
  • Known hepatitis B surface antigen seropositive or known or suspected active hepatitis C infection Note: Patients who have isolated positive hepatitis B core antibody (i.e., in the setting of negative hepatitis B surface antigen and negative hepatitis B surface antibody) must have an undetectable hepatitis B viral load. Patients who have positive hepatitis C antibody may be included if they have an undetectable hepatitis C viral load.
  • Known hepatic cirrhosis or severe pre-existing hepatic impairment
  • Uncontrolled high blood pressure (i.e., systolic blood pressure > 180 mm Hg, diastolic blood pressure > 95 mm Hg).
  • Prolonged rate corrected QT (QTc) interval ≥500 msec, calculated according to institutional guidelines.
  • Left ventricular ejection fraction (LVEF) < 50% as assessed by echocardiogram or radionuclide angiography.
  • Known central nervous system (CNS) involvement.
  • Female patients who are both lactating and breastfeeding or have a positive serum pregnancy test during the screening period or a positive urine pregnancy test on Day 1 before first dose of study drug.
  • Female patients who intend to donate eggs (ova) during the course of this study or 4 months after receiving their last dose of study drug(s).
  • Male patients who intend to donate sperm during the course of this study or 4 months after receiving their last dose of study drug(s).
  • Patients with a currently active second malignancy requiring treatment.
  • Treatment with clinically significant metabolic enzyme inducers within 14 days before the first dose of the study drug. Clinically significant metabolic enzyme inducers are not permitted during this study.

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

United States8 sites

  • Memorial Sloan Kettering at Basking Ridge

    Basking Ridge, New Jersey, 07920

  • Memorial Sloan Kettering Commack

    Commack, New York, 11725

  • Memorial Sloan Kettering Westchester

    Harrison, New York, 10604

  • Memorial Sloan Kettering Monmouth

    Middletown, New Jersey, 07748

  • Memorial Sloan Kettering Bergen

    Montvale, New Jersey, 07645

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Memorial Sloan Kettering Rockville Centre

    Rockville Centre, New York, 11570

  • Memorial Sloan Kettering Nassau

    Uniondale, New York, 11553

Other trials in United States

About this study

Official title: Pevonedistat as a Single Agent and in Combination With Chemotherapy in Patients With Malignant Mesothelioma

The purpose of this study is to test any good and bad effects of activity pevonedistat taken alone, and also to test the safety of pevonedistat in combination with standard chemotherapy, pemetrexed/cisplatin.

Conditions
Mesothelioma
Being tested
pevonedistat, Pemetrexed and cisplatin
Keywords
Pevonedistat, Pemetrexed, Cisplatin, 17-361
Medical subject headings
Mesothelioma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • pevonedistatDrug

    Pevonedistat will be administered as an IV infusion at a dose of 50 mg/m2 days 1, 3, and 5 of a 21-day cycle.Treatment will be administered as an outpatient.

  • Pemetrexed and cisplatinDrug

    Pemetrexed, 500 mg/m2 and cisplatin, 75 mg/m2, will be given at fixed doses on day 1 of each cycle.

Study groups in NCT03319537
Study groupRoleWhat they receive
PevonedistatExperimentalNot described
Receives: Drug: pevonedistat
pevonedistat in combination with pemetrexed and cisplatinExperimentalNot described
Receives: Drug: pevonedistat; Drug: Pemetrexed and cisplatin

What is being measured

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

  1. Number of Patients Who Have a Clinical Benefit Rate (CBR) (Cohort 1)

    The CBR is defined as the proportion of patients CR, PR or SD at 18 weeks based on RECIST criteria.

    Measured: at 18 weeks post initiation of treatment

  2. Maximum Tolerated Dose (MTD) (Cohort 2)

    If none of the initial cohort of 3 has a dose-limited toxicity the dose level will be escalated. If one has a DLT that dose level will be expanded with 3 more patients. Dose escalation will stop if ≥2 DLTs are seen at a dose level. The MTD is defined as the highest dose level at which no more than 1 of the 6 patients at that level has a DLT. If no patient in the 3-patient cohort has a DLT and the dose level is under final consideration of the MTD, an additional three patients will be treated at that level for confirmation.

    Measured: 3 year

Timeline

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

  1. First posted24 Oct 2017
  2. Study start5 Oct 2017
  3. Primary completion5 Jun 2023
  4. Study completion5 Jun 2023

Why it stopped: Sponsor terminated study agreement

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
This study is a single institution trial with two cohorts to test the efficacy of the NEDD8 inhibitor, pevonedistat as a single agent in patients with NF2 mutant MM (Cohort 1), and also to test the safety of pevonedistat in combination with standard chemotherapy, pemetrexed/cisplatin (Cohort 2).
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03319537
Sponsor's protocol ID
17-361
Status last verified
Apr 2024
First submitted
20 Oct 2017
Last updated
23 May 2024
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing pevonedistat and Pemetrexed and cisplatin in people with Mesothelioma, run by Memorial Sloan Kettering Cancer Center at 8 sites 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 32 inclusion and 32 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 23 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites 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 combined 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.

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 23 May 2024). 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?

Number of Patients Who Have a Clinical Benefit Rate (CBR) (Cohort 1) (time frame: at 18 weeks post initiation of treatment). The study lists 2 primary outcomes in all. 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 NCT03319537.

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 May 2024.

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