Pevonedistat + Chemotherapy for Non-Small Cell Lung Cancer

Recruiting at 12 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must be taking: Checkpoint inhibitors

Must not be taking: Investigational agents

Disqualifiers: Uncontrolled illness, Psychiatric illness, Cardiopulmonary disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: 12 weeks

27 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot take certain medications that are strong enzyme inducers, like ritonavir, efavirenz, or nevirapine, during the study.

What data supports the effectiveness of the drug combination of Pevonedistat, Carboplatin, and Paclitaxel for treating non-small cell lung cancer?

Research shows that the combination of Paclitaxel and Carboplatin is widely used and effective in treating advanced non-small cell lung cancer, with response rates up to 34% and a 1-year survival rate of 42%. This suggests that adding Pevonedistat to this combination could potentially enhance its effectiveness. ^{1 2 3 4 5}

Is the combination of Pevonedistat, Carboplatin, and Paclitaxel safe for humans?

Studies on Carboplatin and Paclitaxel, used together for non-small cell lung cancer, show that they generally have minimal toxicity, with some patients experiencing mild side effects like myelosuppression (a decrease in blood cell production). There is no specific safety data for Pevonedistat in these studies, but the combination of Carboplatin and Paclitaxel is considered to have a manageable safety profile. ^{3 4 6 7 8}

What makes the drug Pevonedistat combined with chemotherapy unique for treating non-small cell lung cancer?

Pevonedistat is a novel drug that, when combined with chemotherapy drugs like carboplatin and paclitaxel, offers a new approach to treating non-small cell lung cancer by potentially enhancing the effectiveness of these existing chemotherapy agents. ^{1 2 3 9 10}

What is the purpose of this trial?

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.

Research Team

Ticiana A Leal

Principal Investigator

JHU Sidney Kimmel Comprehensive Cancer Center LAO

Eligibility Criteria

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.

Inclusion Criteria

I can understand and am willing to sign the consent form, or I have someone who can do it for me.

I agree to use effective birth control during the study.

My liver function tests are within the required range.

Exclusion Criteria

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

I have severe liver problems or cirrhosis.

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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive paclitaxel, carboplatin, and pevonedistat intravenously. Treatment repeats every 21 days for at least 4 cycles.

12 weeks

4 cycles, each with multiple visits for drug administration

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up occurs at 30 days, every 3 months for 1 year, and then every 6 months until 5 years.

5 years

Regular follow-up visits

Treatment Details

Interventions

• Carboplatin
• Paclitaxel
• Pevonedistat

Trial Overview 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.

Participant Groups

Group I: Treatment (paclitaxel, carboplatin, pevonedistat) Experimental Treatment 3 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.

Carboplatin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

The combination of paclitaxel and carboplatin has shown promising results in treating advanced non-small-cell lung cancer (NSCLC), with reported 1-year survival rates as high as 54%, making it a widely used regimen in clinical practice.

This combination therapy has been effective without additional toxicity, allowing for full doses of both drugs to be administered, and is currently being evaluated in ongoing studies for earlier stages of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel/carboplatin in the treatment of non-small-cell lung cancer. Belani, CP.[2015]

In a multicenter study involving 130 patients with advanced non-small cell lung cancer (NSCLC), the combination of paclitaxel and carboplatin resulted in a moderate response rate of 23.8%, indicating its efficacy as a treatment option.

Both high-dose (200 mg/m2) and low-dose (175 mg/m2) paclitaxel regimens were well tolerated, with myelosuppression being the most significant side effect, but differences in toxicity between the two doses were minimal.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multi-center study of two dose levels of paclitaxel with carboplatin in locally advanced and metastatic non-small cell lung cancer (NSCLC). Glorieux, P., Ortmanns, P., Marien, S., et al.[2015]

In a phase II trial involving 51 patients with untreated stage IIIB and IV non-small cell lung cancer, the combination of carboplatin and paclitaxel showed an overall response rate of 27.5%, indicating some effectiveness in treating this aggressive cancer.

The treatment was generally well-tolerated, with modest toxicity levels; only 5% of patients experienced severe nonhematologic side effects, suggesting that this combination therapy could be a safe option for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel plus carboplatin for advanced lung cancer: preliminary results of a Vanderbilt University phase II trial--LUN-46. Johnson, DH., Paul, DM., Hande, KR., et al.[2015]

In a phase II study involving 155 patients with advanced non-small-cell lung cancer, the combination of paclitaxel and carboplatin resulted in a 34% objective response rate, indicating significant efficacy in treating this cancer type.

The treatment was generally safe, with manageable side effects like leukopenia and peripheral neuropathy, and a median survival of 8 months, along with a 1-year survival rate of 42%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

One-hour paclitaxel plus carboplatin for advanced non-small-cell lung cancer. Greco, FA., Hainsworth, JD.[2015]

In a meta-analysis of 486 patients with advanced non-squamous non-small cell lung cancer, the pemetrexed plus carboplatin regimen at 5 mg/min•mL (PCb5) showed a significantly lower incidence of treatment-emergent adverse events (TEAEs) compared to the 6 mg/min•mL (PCb6) regimen, including less thrombocytopenia, anemia, and fatigue.

Despite the differences in safety profiles, both PCb5 and PCb6 regimens demonstrated similar efficacy outcomes in terms of overall survival and progression-free survival, indicating that PCb5 may be a safer option without compromising treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meta-analysis of pemetrexed plus carboplatin doublet safety profile in first-line non-squamous non-small cell lung cancer studies. Okamoto, I., Schuette, WH., Stinchcombe, TE., et al.[2018]

In a study involving 180 patients with advanced non-small cell lung cancer (NSCLC), pemetrexed-carboplatin did not show superior efficacy compared to paclitaxel-carboplatin, with similar progression-free survival (PFS) rates and overall survival after a median follow-up of 17 months.

While both treatment regimens had comparable overall toxicities, the paclitaxel-carboplatin group experienced higher rates of alopecia and peripheral neuropathy, indicating a difference in side effects between the two treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Open-Label Randomized Controlled Trial Comparing the Efficacy and Safety of Pemetrexed-Carboplatin versus (Weekly) Paclitaxel-Carboplatin as First-Line Chemotherapy in Advanced Non-Squamous Non-Small Cell Lung Cancer. Yadav, A., Malik, PS., Khurana, S., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Paclitaxel/carboplatin in the treatment of non-small-cell lung cancer. [2015]

2. United States pubmed.ncbi.nlm.nih.gov

A phase I/II trial of paclitaxel, carboplatin, and gemcitabine in untreated patients with advanced non-small cell lung cancer. [2022]

3. Greece pubmed.ncbi.nlm.nih.gov

Multi-center study of two dose levels of paclitaxel with carboplatin in locally advanced and metastatic non-small cell lung cancer (NSCLC). [2015]

4. United States pubmed.ncbi.nlm.nih.gov

Paclitaxel plus carboplatin for advanced lung cancer: preliminary results of a Vanderbilt University phase II trial--LUN-46. [2015]

5. United States pubmed.ncbi.nlm.nih.gov

One-hour paclitaxel plus carboplatin for advanced non-small-cell lung cancer. [2015]

6. England pubmed.ncbi.nlm.nih.gov

Meta-analysis of pemetrexed plus carboplatin doublet safety profile in first-line non-squamous non-small cell lung cancer studies. [2018]

7. Poland pubmed.ncbi.nlm.nih.gov

A double-blind, randomized phase II study of dicycloplatin plus paclitaxel versus carboplatin plus paclitaxel as first-line therapy for patients with advanced non-small-cell lung cancers. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Paclitaxel and carboplatin adjuvant therapy alone or with radiotherapy for resected nonsmall cell lung carcinoma: a feasibility study of the Minnie Pearl Cancer Research Network. [2019]

9. Singapore pubmed.ncbi.nlm.nih.gov

Tumor response and clinical toxicity associated with second-line chemotherapy regimens for advanced non-squamous non-small cell lung cancer: A retrospective cohort study. [2018]

10. Switzerland pubmed.ncbi.nlm.nih.gov

An Open-Label Randomized Controlled Trial Comparing the Efficacy and Safety of Pemetrexed-Carboplatin versus (Weekly) Paclitaxel-Carboplatin as First-Line Chemotherapy in Advanced Non-Squamous Non-Small Cell Lung Cancer. [2021]