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Alkylating Agent

Pevonedistat + Chemotherapy for Non-Small Cell Lung Cancer

Phase 2

Waitlist Available

Led By Ticiana A Leal

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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

Glomerular filtration rate (GFR) > 30 mL/min/1.73 m^2

Must not have

Known moderate to severe chronic obstructive pulmonary disease, interstitial lung disease, and pulmonary fibrosis

Known hepatic cirrhosis or severe pre-existing hepatic impairment

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2.5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a combination of drugs to treat patients with stage IIIB or IV non-small cell lung cancer. The drugs work in different ways to stop the growth of cancer cells. Giving the drugs together may work better than giving other standard chemotherapy drugs.

Who is the study for?

This trial is for adults with stage IIIB or IV non-small cell lung cancer (NSCLC) who have previously been treated with immunotherapy. They must have a life expectancy of at least 12 weeks, acceptable liver and kidney function, controlled CNS metastases if present, and no severe heart or lung conditions. Participants need to agree to use contraception and cannot be pregnant.

What is being tested?

The study tests the effectiveness of combining MLN4924 (Pevonedistat) with Carboplatin and Paclitaxel in NSCLC patients who didn't respond well to prior treatments. It aims to see if this combination is better than standard chemotherapy by blocking enzymes that help cancer cells grow.

What are the potential side effects?

Potential side effects include nausea, fatigue, hair loss from chemotherapy drugs like Carboplatin and Paclitaxel; Pevonedistat may cause blood count issues or organ inflammation. Side effects can vary based on individual health conditions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My condition worsened after treatment with PD-1/PD-L1 inhibitors.

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My kidney function, measured by GFR, is above 30.

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I have NSCLC with specific genetic changes and have been treated with FDA-approved targeted therapy.

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I am 18 years old or older.

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I am fully active or can carry out light work.

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My lung cancer is at an advanced stage and cannot be surgically removed.

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My brain metastases are treated, symptoms stable for 2 weeks, and I'm off or reducing steroids.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have a serious lung condition like COPD, lung scarring, or fibrosis.

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I have severe liver problems or cirrhosis.

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I have allergies to certain cancer drugs similar to MLN4924, carboplatin, or paclitaxel.

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I have a known heart or lung condition.

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I have a serious irregular heartbeat.

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I haven't had chemotherapy or radiotherapy in the last 2 weeks.

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I haven't had major surgery in the last 14 days and don't plan any during the study.

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I will not donate eggs during the study or for 4 months after the last dose.

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I have a bleeding disorder that is not under control.

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I am on medication for my symptomatic pulmonary hypertension.

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I have severe nerve pain or numbness in my hands or feet.

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I do not have a life-threatening illness unrelated to my cancer.

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My high blood pressure is not under control.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2.5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2.5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2.5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Number of Participants With an Overall Response

Secondary study objectives

Duration of Progression Free Survival (PFS)

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

Overall Survival (OS)

Other study objectives

ATF3 Expression Levels

B2M Expression Levels

GCLM Expression Levels

+13 more

Side effects data

From 2024 Phase 3 trial • 454 Patients • NCT03268954

41%

Constipation

37%

Anaemia

35%

Neutropenia

34%

Thrombocytopenia

29%

Nausea

25%

Pyrexia

23%

Diarrhoea

21%

Vomiting

19%

Asthenia

16%

Febrile neutropenia

15%

Fatigue

14%

Oedema peripheral

11%

Cough

11%

Decreased appetite

11%

Arthralgia

11%

Dizziness

11%

Pneumonia

10%

Platelet count decreased

10%

Epistaxis

10%

Insomnia

10%

Pain in extremity

10%

Dyspnoea

Hypokalaemia

Upper respiratory tract infection

Headache

Injection site erythema

Back pain

Neutrophil count decreased

Urinary tract infection

Hyperuricaemia

Abdominal pain

Oropharyngeal pain

Blood creatinine increased

Hypertension

Pruritus

Leukopenia

Sepsis

Alanine aminotransferase increased

Aspartate aminotransferase increased

Hypomagnesaemia

Abdominal pain upper

White blood cell count decreased

Fall

Hypotension

Myalgia

Abnormal loss of weight

Injection site pain

Contusion

Lower respiratory tract infection

Septic shock

Haemorrhoids

Hypophosphataemia

Stomatitis

Blood bilirubin increased

Musculoskeletal pain

COVID-19 pneumonia

Infection

Respiratory tract infection

General physical health deterioration

Multiple organ dysfunction syndrome

Respiratory failure

Acute respiratory failure

Organising pneumonia

Gastrointestinal haemorrhage

Cardiac failure

COVID-19

Cerebrovascular accident

Haemorrhage intracranial

Myocardial infarction

Acute myeloid leukaemia

Malignant melanoma

Soft tissue necrosis

Intestinal obstruction

Pleural effusion

Fluid overload

100%

80%

60%

40%

20%

Study treatment Arm

Azacitidine 75 mg/m^2

Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment (paclitaxel, carboplatin, pevonedistat)Experimental Treatment3 Interventions

Patients 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Carboplatin

2014

Completed Phase 3

~6120

Paclitaxel

2011

Completed Phase 4

~5450