Osimertinib + Chemotherapy for Lung Cancer

(NeoADAURA Trial)

Not currently recruiting at 183 trial locations

Overseen By AstraZeneca Cancer Study Locator

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must not be taking: CYP3A4 inducers

Disqualifiers: ILD, Prior malignancy, Pre-op radiotherapy, others

Stay on Your Current Meds You can continue your current medications while participating

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates new treatments for individuals with EGFRm Non-Small Cell Lung Cancer that can be surgically removed. Researchers are testing whether adding osimertinib, a targeted therapy, either alone or with chemotherapy, is more effective than chemotherapy alone. The trial includes three groups: one receives a placebo with chemotherapy, another receives osimertinib with chemotherapy, and the last receives only osimertinib. Suitable participants have a lung tumor that can be completely removed and possess specific genetic mutations sensitive to certain treatments. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatments.

Will I have to stop taking my current medications?

The trial requires that you stop using medications or herbal supplements that are strong inducers of cytochrome P450 (CYP) 3A4 at least 3 weeks before starting the study treatment.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that osimertinib, whether used alone or with chemotherapy, is generally well-tolerated by patients with lung cancer. One study found that about 22% of patients taking osimertinib alone experienced severe side effects, but most side effects were mild to moderate. Another study found that combining osimertinib with chemotherapy remains manageable for patients.

Overall, these findings suggest that many patients can handle osimertinib, both by itself and with chemotherapy. While some side effects may occur, they are often not severe for most people. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for lung cancer because they offer several promising advancements. Unlike the standard of care, which typically involves platinum-based chemotherapies like carboplatin and cisplatin, the investigational treatment includes osimertinib, a targeted therapy that specifically inhibits the EGFR (epidermal growth factor receptor) mutation. This precise targeting can potentially lead to better outcomes and fewer side effects compared to traditional chemotherapy. Additionally, the combination of osimertinib with chemotherapy could enhance the effectiveness by attacking the cancer from multiple angles, offering hope for improved survival rates and quality of life for patients.

What evidence suggests that this trial's treatments could be effective for lung cancer?

Research has shown that osimertinib is very effective in treating non-small cell lung cancer (NSCLC) with specific genetic changes known as EGFR mutations. In this trial, some participants will receive osimertinib with chemotherapy, which has helped patients live for nearly four years on average, marking a significant improvement. This combination consistently extends patients' lives, regardless of their cancer stage. Other participants will receive osimertinib alone, which also works well and is generally easy for patients to tolerate. These findings suggest that both the drug combination and osimertinib alone are promising options for improving outcomes in lung cancer patients with these specific genetic markers. ^{2 3 4 6 7}

Who Is on the Research Team?

Jamie E Chaft, MD

Principal Investigator

Memorial Sloan Kettering, USA

Walter Weder, MD

Principal Investigator

Thoraxchirurgie Bethanien, Switzerland

Masahiro Tsuboi

Principal Investigator

National Cancer Center Hospital East, Japan

Are You a Good Fit for This Trial?

This trial is for adults with a specific type of lung cancer (non-squamous NSCLC) that can be surgically removed. Patients must have certain EGFR mutations, good performance status, and no history of severe lung conditions or other cancers within the last 2 years. Prior cancer treatments for NSCLC are not allowed.

Inclusion Criteria

My non-squamous NSCLC is at stage II - IIIB N2 and can be completely removed with surgery.

I can care for myself and perform light activities without help.

My lung cancer can be fully removed by surgery, as confirmed by a specialized team.

Exclusion Criteria

I have had lung inflammation or damage that needed steroids.

My lung cancer is a mix of small cell and non-small cell types.

I am not using, nor can I stop using, certain medications or supplements that affect my liver enzymes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive neoadjuvant osimertinib as monotherapy or in combination with chemotherapy, or standard of care chemotherapy alone

12 weeks

Surgery

Participants undergo surgery to remove the tumor after neoadjuvant treatment

Follow-up

Participants are monitored for safety, effectiveness, and survival outcomes after surgery

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Cisplatin
• Osimertinib
• Pemetrexed

Trial Overview

The study tests Osimertinib alone or combined with chemotherapy against standard-of-care chemotherapy in patients who can undergo surgery to remove their lung cancer. It's a Phase III trial where participants are randomly assigned to one of three groups.

How Is the Trial Designed?

Group I: Arm 3: Osimertinib monotherapy Experimental Treatment 1 Intervention

Osimertinib 80 mg QD (Dose may be reduced to 40 mg QD at the discretion of the investigator)

Group II: Arm 2: Osimertinib with platinum-based chemotherapy Experimental Treatment 4 Interventions

Osimertinib 80 mg QD (Dose may be reduced to 40 mg QD at the discretion of the investigator) plus investigator's choice of platinum-based standard of care chemotherapy (pemetrexed/carboplatin or pemetrexed/cisplatin)

Group III: Arm 1: Placebo with platinum-based chemotherapy Placebo Group 4 Interventions

Placebo plus investigator's choice of platinum-based standard of care chemotherapy (pemetrexed/carboplatin or pemetrexed/cisplatin)

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?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Published Research Related to This Trial

Cisplatin, carboplatin, and oxaliplatin, while structurally similar, have different therapeutic uses and efficacy profiles; for example, carboplatin is less effective than cisplatin for certain cancers but comparable in others like ovarian cancer.

Oxaliplatin is particularly effective for colorectal cancer when combined with 5-fluorouracil and folinic acid, marking it as a significant advancement in treatment options for this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Platinum compounds: metabolism, toxicity and supportive strategies]. Lipp, HP., Hartmann, JT.[2013]

Pemetrexed, when combined with cisplatin, significantly improves median survival in patients with malignant pleural mesothelioma, with a median survival of 12.1 months compared to 9.3 months for cisplatin alone, based on a phase III trial involving 448 patients.

The drug works by inhibiting key enzymes involved in DNA synthesis, but it can cause side effects like myelosuppression, neutropenia, and fatigue, necessitating supportive care with folic acid, vitamin B12, and corticosteroids during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA drug approval summaries: pemetrexed (Alimta). Hazarika, M., White, RM., Johnson, JR., et al.[2022]

In a study involving 812 patients with malignant pleural mesothelioma (MPM), single-agent pemetrexed showed promising efficacy, with a median time to progressive disease of 6.0 months for chemonaïve patients and an overall response rate of 10.5%.

The treatment was well-tolerated, exhibiting mild hematologic toxicity, primarily neutropenia, in less than 18% of patients, indicating a favorable safety profile for pemetrexed in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-agent pemetrexed for chemonaïve and pretreated patients with malignant pleural mesothelioma: results of an International Expanded Access Program. Taylor, P., Castagneto, B., Dark, G., et al.[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 of 903 patients with malignant pleural mesothelioma (MPM), pemetrexed combined with cisplatin was found to be generally well tolerated, with a low treatment-associated death rate of 0.8% and an interstitial lung disease (ILD) incidence of 0.9%.

The overall response rate to treatment was 25%, and the six-month survival rate was estimated at 75.9%, indicating that pemetrexed is effective in managing MPM, consistent with previous clinical trial results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of pemetrexed in patients with malignant pleural mesothelioma based on all-case drug-registry study. Kuribayashi, K., Voss, S., Nishiuma, S., et al.[2015]

Pemetrexed (Alimta) is an effective treatment for mesothelioma and shows comparable survival rates to docetaxel in advanced non-small-cell lung cancer (NSCLC) while causing significantly fewer and less severe side effects.

In combination with platinum agents, pemetrexed has demonstrated significant activity and a favorable toxicity profile, making it a promising option for treating thoracic malignancies and warranting further research with other novel drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed in advanced NSCLC: a review of the clinical data. Zinner, RG., Fossella, FV., Herbst, RS.[2015]

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]

Pemetrexed, commonly used for treating mesothelioma and lung adenocarcinoma, has been associated with a rare case of communicating hydrocephalus in a patient undergoing maintenance therapy, highlighting a potential unexpected toxicity.

As the use of pemetrexed increases, especially in maintenance settings, healthcare providers should be vigilant for unusual side effects, including neurological complications, during long-term treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed and communicating hydrocephalus. Son, CO., Mott, FE.[2021]

In a study of 53 patients with advanced non-small cell lung cancer (NSCLC) who had previously undergone platinum-based chemotherapy, treatment with pemetrexed plus cisplatin or carboplatin resulted in a median overall survival of 10 months and a median progression-free survival of 6 months.

The treatment was generally well-tolerated, with only a small percentage of patients experiencing severe side effects, such as grade 3 or 4 leukopenia and thrombocytopenia, indicating that pemetrexed combined with platinum-based drugs can be a safe option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed plus cisplatin/carboplatin in previously treated locally advanced or metastatic non-small cell lung cancer patients. Zhang, GZ., Jiao, SC., Meng, ZT.[2021]

Carboplatin has shown comparable efficacy to cisplatin in treating non-small cell lung cancer (NSCLC) and can be effectively used in combination chemotherapy, providing similar survival benefits.

Ongoing clinical trials are exploring various strategies to optimize carboplatin use, including dose adjustments, combinations with other treatments like stem-cell support and radiation therapy, and interactions with new agents like TAXOL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin in the treatment of non-small cell lung cancer: a review. Comis, RL.[2018]

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