AzTrials
AzTrials

Metastatic Lung Non-Small Cell Squamous CarcinomaPhase 2NCT03965689

Testing the Combination of MLN4924 (Pevonedistat), Carboplatin, and Paclitaxel in Patients With Advanced Non-small Cell Lung Cancer (NSCLC) Who Have Previously Been Treated With Immunotherapy

A Phase 2 study testing Carboplatin, Paclitaxel and Pevonedistat in people with Metastatic Lung Non-Small Cell Squamous Carcinoma and Metastatic Lung Non-Squamous Non-Small Cell Carcinoma, run by National Cancer Institute (NCI) at 10 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

This phase II trial studies how well MLN4924 (pevonedistat), carboplatin, and paclitaxel work in treating patients with stage IIIB or IV non-small cell lung cancer. Pevonedistat may stop the growth of cancer 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?
Carboplatin, Paclitaxel and Pevonedistat
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
27 participants
Where
10 sitesUnited States
Study dates
16 Apr 2020to 20 Mar 2027
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

  • Patients must be >= 18 years old. Because no dosing or adverse event (AE) data are currently available on the use of MLN4924 (pevonedistat) in combination with carboplatin and paclitaxel in patients < 18 years of age, children are excluded from this study, but may be eligible for future pediatric trials.
  • Patients must have histologically confirmed stage IIIB or IV NSCLC (squamous or nonsquamous) that is metastatic or unresectable.
  • Patients must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
  • Patients must have progressed on prior treatment with checkpoint inhibitor (PD-1/PD-L1 inhibitors) either as a single-agent therapy or in combination, as below. Patients will be eligible if there is a contra-indication to checkpoint inhibitor therapy.
  • Patients who have progressed after receiving a checkpoint inhibitor in combination with a platinum-based doublet, as first-line treatment for NSCLC.
  • Patients who have progressed on checkpoint inhibitor as second-line therapy, after receiving a platinum-based doublet as first-line therapy.
Show all 35Show fewer
  • Patients who have progressed on platinum-based doublet as second-line therapy, after receiving a checkpoint inhibitor as first-line therapy.
  • Patients must have disease progression on or after platinum-based chemotherapy for metastatic disease or within 6 months of completion of platinum-based chemotherapy administration as adjuvant/neoadjuvant chemotherapy or concurrent chemoradiation.
  • Absolute neutrophil count >= 1,500/mcL.
  • Platelet count >= 150,000/mcL.
  • Total bilirubin =< 1 x institutional upper limit of normal (ULN). Patients with Gilbert's syndrome may enroll if direct bilirubin =< 1.5 x institutional ULN.
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) / alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3.0 x institutional ULN. Patients with metastatic liver disease may enroll if =< 5 x ULN.
  • Glomerular filtration rate (GFR) > 30 mL/min/1.73 m^2.
  • Known human immunodeficiency virus (HIV) positive patients who meet the following criteria will be considered eligible:
  • CD4 count > 350 cells/mm^3.
  • Undetectable viral load within the last six months.
  • HIV positive patients must be stable on highly active antiretroviral therapy (HAART). Clinically significant metabolic enzyme inducers are not permitted during this study (e.g., ritonavir, efavirenz, nevirapine).
  • No history of acquired immune deficiency syndrome (AIDS)-defining opportunistic infections.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
  • Life expectancy >= 12 weeks.
  • Patients are eligible if central nervous system (CNS) metastases are adequately treated and neurological symptoms have returned to baseline or are controlled for at least 2 weeks prior to enrollment. In addition, subjects must be either off corticosteroids, or on stable or decreasing dose of steroids. Patients with leptomeningeal disease are excluded.
  • The effects of MLN4924 (pevonedistat) on the developing human fetus are unknown. For this reason and because agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study or within 4 months of completion, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of MLN4924 (pevonedistat) administration.
  • 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 postvasectomy), 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.)
  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
  • Left ventricular ejection fraction (LVEF) >= 50% as assessed by echocardiogram or radionuclide angiography.
  • Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible.
  • Patients with NSCLC harboring genomic aberrations (e.g. sensitizing EGFR, ALK, ROS1, NTRK, BRAF V600E mutation positive) must have received prior treatment with Food and Drug Administration (FDA) approved targeted therapy for patients for which FDA approved targeted therapies is available.

Who cannot join

  • Patients who have not recovered from AEs due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1) with the exception of alopecia and neuropathy.
  • Patients who are receiving any other investigational agents.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to MLN4924 (pevonedistat), carboplatin, or paclitaxel.
  • Patients who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study.
  • Patients with uncontrolled intercurrent illness.
  • Patients with psychiatric illness/social situations that would limit compliance with study requirements.
Show all 29Show fewer
  • Pregnant women are excluded from this study because MLN4924 (pevonedistat), carboplatin, and paclitaxel have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with MLN4924 (pevonedistat), breastfeeding must be discontinued if the mother is treated with MLN4924 (pevonedistat). These potential risks may also apply to other agents used in this study.
  • 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).
  • Known cardiopulmonary disease defined as:
  • Unstable angina;
  • Congestive heart failure (New York Heart Association [NYHA] class III or IV;);
  • Myocardial infarction within 6 months prior to first dose (patients who had ischemic heart disease such as acute coronary syndrome [ACS], myocardial infarction, and/or revascularization greater than 6 months before screening and who are without cardiac symptoms may enroll);
  • Symptomatic cardiomyopathy;
  • Clinically significant arrhythmia:
  • History of polymorphic ventricular fibrillation or torsade de pointes,
  • Permanent atrial fibrillation, defined as continuous atrial fibrillation for >= 6 months,
  • Persistent atrial fibrillation, defined as sustained atrial fibrillation lasting > 7 days and/or requiring cardioversion in the 4 weeks before screening,
  • Grade 3 atrial fibrillation defined as symptomatic and incompletely controlled medically, or controlled with device (e.g., pacemaker), or ablation in the past 6 months and
  • Patients with paroxysmal atrial fibrillation or grade < 3 atrial fibrillation for period of at least 6 months are permitted to enroll provided that their rate is controlled on a stable regimen.
  • Clinically symptomatic pulmonary hypertension requiring pharmacologic therapy.
  • Peripheral neuropathy that is grade >= 3, or grade 2 with pain on clinical examination during the screening period.
  • Uncontrolled high blood pressure (i.e., systolic blood pressure > 180 mmHg, diastolic blood pressure > 95 mmHg).
  • Prolonged rate corrected QT (QTc) interval >= 500 msec, calculated according to institutional guidelines.
  • Known moderate to severe chronic obstructive pulmonary disease, interstitial lung disease, and pulmonary fibrosis.
  • Major surgery within 14 days before the first dose of any study drug or a scheduled surgery during study period.
  • Life-threatening illness unrelated to cancer.
  • Patients with uncontrolled coagulopathy or bleeding disorder.
  • Known hepatic cirrhosis or severe pre-existing hepatic impairment.

Trial locations and contacts

10 sites in 1 country.

10 sites in 1 country

United States10 sites

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • Los Angeles General Medical Center

    Los Angeles, California, 90033

  • USC / Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • University of Wisconsin Carbone Cancer Center - University Hospital

    Madison, Wisconsin, 53792

  • Rutgers Cancer Institute of New Jersey

    New Brunswick, New Jersey, 08903

  • USC Norris Oncology/Hematology-Newport Beach

    Newport Beach, California, 92663

  • Moffitt Cancer Center-International Plaza

    Tampa, Florida, 33607

  • Moffitt Cancer Center - McKinley Campus

    Tampa, Florida, 33612

  • Moffitt Cancer Center

    Tampa, Florida, 33612

  • MedStar Georgetown University Hospital

    Washington D.C., District of Columbia, 20007

Other trials in United States

About this study

Official title: A Phase 2 Study of MLN4924 (Pevonedistat) in Combination With Carboplatin and Paclitaxel in Advanced NSCLC Previously Treated With Immunotherapy

This phase II trial studies how well MLN4924 (pevonedistat), carboplatin, and paclitaxel work in treating patients with stage IIIB or IV non-small cell lung cancer. Pevonedistat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as carboplatin and paclitaxel, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving pevonedistat together with carboplatin and paclitaxel may work better in treating patients with non-small cell lung cancer when compared with other standard chemotherapy drugs.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To determine the overall response rate (ORR) of patients with advanced non-small cell lung cancer (NSCLC) treated with pevonedistat (MLN4924 [pevonedistat]) in combination with carboplatin and paclitaxel.

SECONDARY OBJECTIVES:

  1. To estimate the progression-free survival (PFS) of patients with advanced NSCLC treated with MLN4924 (pevonedistat) in combination with carboplatin and paclitaxel.

II. To estimate the overall survival (OS) of patients with advanced NSCLC treated with MLN4924 (pevonedistat) in combination with carboplatin and paclitaxel.

III. To evaluate the safety profile of MLN4924 (pevonedistat) in combination with carboplatin and paclitaxel.

CORRELATIVE OBJECTIVES:

  1. To evaluate expression of nuclear factor-erythroid 2 p45-related factor 2 (NRF2) target genes NAD(P)H: quinone oxidoreductase1 (NQO1) and the cysteine/glutamate antiporter solute carrier family 7 member 11 (SCL7A11).

II. To determine expression of pharmacodynamic markers induced by neural precursor cell expressed developmentally downregulated protein 8 (NEDD-8) activating enzyme (NAE) inhibition: cyclic AMP-dependent transcription factor (ATF3), beta 2 microglobulin (B2M), glutamate-cysteine ligase regulatory subunit (GCLM), glutathione-disulfide reductase (GSR), deoxyribonucleic acid (DNA)-3-methyladenine (MAG1), ribosomal protein lateral stalk subunit P0 (RPLPO), sulfiredoxin-1 (SRXN1), thioredoxin reductase 1 (TXNRD1), and ubiquitin-conjugating enzyme (UBC).

III. To perform qualitative assessment of tumor NAE1 and ubiquitin-conjugating enzyme E2 M (UBC12) protein expression at baseline.

IV. To assess circulating tumor cells (CTCs) for DNA damage repair pathway alterations (i.e., gamma H2AX induction, RAD51).

  1. To evaluate pharmacokinetic (PK) parameters of MLN4924 (pevonedistat) when given in combination with paclitaxel and carboplatin.

OUTLINE:

Patients receive paclitaxel intravenously (IV) over 3 hours on day 1, carboplatin IV over 30-60 minutes on day 1, and pevonedistat IV over 1 hour on days 1, 3, and 5. Treatment repeats every 21 days for at least 4 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, all patients without disease progression are followed up at 30 days, every 3 months for 1 year and then every 6 months until 5 years from end of study treatment.

Being tested
Carboplatin, Paclitaxel, Pevonedistat
Medical subject headings
Lung Neoplasms

What participants receive

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

  • CarboplatinDrug

    Also called Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino

    Given IV

  • PaclitaxelDrug

    Also called Anzatax, Asotax, Bristaxol, Praxel

    Given IV

  • PevonedistatDrug

    Also called MLN4924, Nedd8-Activating Enzyme Inhibitor MLN4924

    Given IV

Study groups in NCT03965689
Study groupRoleWhat they receive
Treatment (paclitaxel, carboplatin, pevonedistat)ExperimentalPatients receive paclitaxel IV over 3 hours on day 1, carboplatin IV over 30-60 minutes on day 1, and pevonedistat IV over 1 hour on days 1, 3, and 5. Treatment repeats every 21 days for at least 4 cycles in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Carboplatin; Drug: Paclitaxel; Drug: Pevonedistat

What is being measured

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

  1. Number of Participants With an Overall Response

    Response will be evaluated at the time all participants completed treatment and using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in the RECIST criteria. Patients will be re-evaluated for response every 6 weeks. Overall response is the best response achieved during the study. Complete response (CR) is the disappearance of all lesions; Partial response (PR) is a >= 30% decrease in the sum of the target lesions; Progressive disease (PD) is a >= 20% increase in the sum of the lesions; Stable disease (SD) is between a 20 % increase and 30% decrease in the sum of the lesions.

    Measured: Up to 2.5 years

Secondary outcomes (3)

  1. Duration of Progression Free Survival (PFS)

    Progression free survival (PFS) is defined at the time all participants completed treatment and using Response Evaluation Criteria in Solid Tumors (RECIST v1.1) as >= 20% increase in the sum of target lesions, a measurable increase in a non-target lesion, or the appearance of a new lesion. The duration is measured from the start of treatment to the time of progression or death, whichever occurs first.

    Measured: Up to 2.5 years

  2. Overall Survival (OS)

    Defined as the duration of time from start of treatment to time of death or last known date alive at the time all participants completed treatment.

    Measured: Up to 2.5 years

  3. Number of Participants Reporting Grade 3, 4, and 5 Adverse Events

    Evaluated by the revised National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

    Measured: 1 year, on average

Timeline

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

  1. First posted29 May 2019
  2. Study start16 Apr 2020
  3. Primary completion7 Sep 2022
  4. Study completion20 Mar 2027 (estimated)

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
27 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03965689
Sponsor's protocol ID
NCI-2019-03212
Other IDs
NCI-2019-03212, NCI10266, 10266, 10266, UM1CA186691, UM1CA186716
Status last verified
Sep 2026
First submitted
27 May 2019
Last updated
22 Sep 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Carboplatin, Paclitaxel and Pevonedistat in people with Metastatic Lung Non-Small Cell Squamous Carcinoma and Metastatic Lung Non-Squamous Non-Small Cell Carcinoma, run by National Cancer Institute (NCI) at 10 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 35 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: under way, not looking for participants, as of the sponsor's last update on 22 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 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 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 15 Dec 2023). 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 Participants With an Overall Response (time frame: Up to 2.5 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 NCT03965689.

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 22 Sep 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in