Alectinib + Crizotinib for Cancer

Recruiting at 33 trial locations

Overseen By Reference Study ID Number: BO39694 www.roche.com/about_roche/roche_worldwide.htm

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Hoffmann-La Roche

Must be taking: Alectinib, Crizotinib

Must not be taking: CYP3A inhibitors, inducers

Disqualifiers: Pregnancy, Breastfeeding, Serious adverse events, others

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

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

200 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to provide continued treatment with alectinib or crizotinib as applicable to participants with ALK- or RET positive cancer who were previously enrolled in any Roche-sponsored alectinib study and who are deriving continued clinical benefit from alectinib or crizotinib in the parent trial at the time of parent trial closure.

Will I have to stop taking my current medications?

The trial requires that you do not take strong cytochrome P450 (CYP) 3A inhibitors or inducers within 14 days before starting and during treatment with crizotinib. Other medications are not specifically mentioned, so it's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug combination Alectinib and Crizotinib for cancer?

Alectinib has been shown to be effective in treating advanced ALK-positive non-small cell lung cancer (NSCLC), especially in patients who have not responded to Crizotinib. Studies have demonstrated that Alectinib improves progression-free survival and has a good safety profile, making it a promising option for patients with this type of cancer. ^{1 2 3 4 5}

Is the combination of Alectinib and Crizotinib safe for humans?

Alectinib and Crizotinib have been studied for safety in patients with ALK-positive non-small-cell lung cancer. Alectinib generally has a manageable safety profile, with most side effects being mild or moderate, such as liver issues and reduced white blood cell counts. Crizotinib has been compared to Alectinib, with Alectinib showing a favorable safety profile. ^{1 5 6 7 8}

How is the drug combination of Alectinib and Crizotinib unique for cancer treatment?

The combination of Alectinib and Crizotinib is unique because Alectinib is a highly selective ALK inhibitor that has shown improved progression-free survival and better central nervous system outcomes compared to Crizotinib alone in ALK-positive non-small cell lung cancer (NSCLC). This combination may offer enhanced efficacy, especially for patients with brain metastases. ^{1 5 9 10 11}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

This trial is for patients with ALK- or RET-positive cancer who were part of a previous Roche-sponsored alectinib study and are still benefiting from alectinib or crizotinib. They must not be able to switch to commercial supply, agree to contraception if necessary, and cannot join if they're pregnant, breastfeeding, had no benefit in the parent trial, experienced severe side effects that led to discontinuation, or have unresolved serious adverse events.

Inclusion Criteria

I agree to use effective birth control or remain abstinent during and for 3 months after treatment.

I am benefiting from alectinib or crizotinib in a Roche trial but can't switch to commercial supply.

For women who are not postmenopausal (≥ 12 months of non-therapy-induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent or use single or combined contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 3 months after the last dose of study drug

Exclusion Criteria

I don't have any severe side effects from previous treatments that haven't improved.

I stopped taking alectinib or crizotinib before starting the new study drug.

I had to stop my cancer treatment for over 3 weeks because of side effects, but now I'm better or stable.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive continued treatment with alectinib or crizotinib as applicable, following the same dose and schedule as in the parent trial

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Alectinib
• Crizotinib

Trial Overview The study continues treatment with either alectinib or crizotinib for participants previously enrolled in related trials. It aims to provide these drugs when commercial options aren't available and assess long-term benefits and safety for those still showing improvement.

Participant Groups

Group I: Crizotinib Experimental Treatment 1 Intervention

Participants will receive crizotinib at the same dose and schedule and according to the same administration guidelines as they received at the time of discontinuation from the parent trial.

Group II: Alectinib Experimental Treatment 1 Intervention

Participants will receive alectinib at the same dose and schedule and according to the same administration guidelines as they received at the time of discontinuation from the parent trial.

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

Approved in United States as Alecensa for:

• Metastatic ALK-positive non-small cell lung cancer (NSCLC)
• Adjuvant treatment following tumor resection in patients with ALK-positive NSCLC

Approved in European Union as Alecensa for:

• Metastatic ALK-positive non-small cell lung cancer (NSCLC)
• Adjuvant treatment following tumor resection in patients with ALK-positive NSCLC

Who Is Running the Clinical Trial?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Findings from Research

Alectinib is an effective first-line treatment for adults with advanced ALK-positive non-small cell lung cancer (NSCLC), showing significantly improved progression-free survival compared to crizotinib and chemotherapy in clinical trials lasting up to 19 months.

The drug has a manageable safety profile, with most side effects being mild to moderate, making it a recommended option in treatment guidelines for patients with advanced ALK-positive NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alectinib: A Review in Advanced, ALK-Positive NSCLC. Paik, J., Dhillon, S.[2019]

Alectinib is a highly selective ALK inhibitor that has shown effectiveness against most crizotinib resistance mutations and has a favorable safety profile, making it a promising treatment for ALK-positive non-small-cell lung cancer (NSCLC).

The Phase III J-ALEX study demonstrated that alectinib significantly improves progression-free survival compared to crizotinib in treatment-naive ALK-positive NSCLC patients, suggesting it may become the preferred first-line therapy for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alectinib for treatment of ALK-positive non-small-cell lung cancer. Avrillon, V., Pérol, M.[2022]

Alectinib is a highly effective treatment for ALK fusion-gene positive advanced non-small cell lung cancer (NSCLC), with a 93.5% objective response rate in a phase 1-2 study involving ALK inhibitor-naive patients.

The drug is well tolerated, showing no grade 4 adverse events, and has a promising safety profile, with a 76% two-year progression-free survival rate and no progression of CNS lesions in patients with known metastases during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alectinib: a review of its use in advanced ALK-rearranged non-small cell lung cancer. McKeage, K.[2022]

In a study of 211 patients with advanced ALK-positive NSCLC treated with alectinib, those with 40% or more ALK-positive cells experienced significantly better progression-free survival (PFS) and overall survival (OS) compared to those with fewer ALK-positive cells, indicating that the percentage of ALK-positive cells can predict treatment outcomes.

The overall response rate (ORR) was also higher in patients with a higher percentage of ALK-positive cells (87.2% vs. 68.5%), suggesting that alectinib is more effective in patients with a greater presence of ALK-positive tumor cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The percentage of ALK-positive cells and the efficacy of first-line alectinib in advanced non-small cell lung cancer: is it a novel factor for stratification? (Turkish Oncology Group Study). Hizal, M., Bilgin, B., Paksoy, N., et al.[2023]

Alectinib shows a high overall response rate of 70% and a disease control rate of 88% in treating non-small cell lung cancer, based on a meta-analysis of 8 studies involving 626 patients.

While alectinib is generally well-tolerated, it has a higher incidence of certain side effects like myalgia (18%) and anemia (25%) compared to the first-generation ALK inhibitor crizotinib, indicating the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of alectinib in the treatment of ALK+ NSCLC: a systematic review and meta-analysis. Fan, J., Xia, Z., Zhang, X., et al.[2022]

Alectinib demonstrated superior efficacy compared to crizotinib in treating ALK-positive non-small cell lung cancer, with higher overall response rates and longer progression-free survival based on a meta-analysis of three studies involving 697 patients.

Alectinib was also associated with fewer adverse events than crizotinib, indicating it is not only more effective but also better tolerated, supporting its use as a first-line treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Clinical Efficacy of Alectinib Versus Crizotinib in ALK-Positive Non-Small Cell Lung Cancer: A Meta-Analysis. Tang, H., Jin, L., Zhang, Z., et al.[2022]

Alectinib was found to have a favorable safety profile in a large-scale study of 1251 patients with ALK-positive non-small-cell lung cancer (NSCLC) in Japan, with 53.6% experiencing adverse drug reactions (ADRs), mostly mild to moderate in severity.

The study indicated that overall survival rates were significantly better in patients with good performance status, those who had not previously received crizotinib, and those receiving alectinib as a first-line treatment, suggesting its effectiveness in improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of alectinib in a real-world surveillance study in patients with ALK-positive non-small-cell lung cancer in Japan. Masuda, N., Ohe, Y., Gemma, A., et al.[2021]

In the phase III ALEX study involving patients with ALK+ non-small-cell lung cancer, alectinib showed superior efficacy compared to crizotinib, with patients reporting clinically meaningful improvements in lung cancer symptoms for a longer duration.

Alectinib also demonstrated better tolerability and health-related quality of life, with patients experiencing longer periods of symptom improvement and fewer treatment-related side effects compared to those on crizotinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes from the randomized phase III ALEX study of alectinib versus crizotinib in patients with ALK-positive non-small-cell lung cancer. Pérol, M., Pavlakis, N., Levchenko, E., et al.[2020]

In a study of 34 untreated ALK-positive NSCLC patients with brain metastases, alectinib demonstrated significantly better progression-free survival (PFS) compared to crizotinib, with a median PFS of 32.8 months versus 8.0 months.

Alectinib also showed superior efficacy in treating brain lesions, with a median PFS that was not reached, while crizotinib had a median PFS of 8.5 months, indicating that alectinib may be a more effective treatment option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alectinib Together with Intracranial Therapies Improved Survival Outcomes in Untreated ALK-Positive Patients with Non-Small-Cell Lung Cancer and Symptomatic and Synchronic Brain Metastases: A Retrospective Study. Yin, Q., Li, P., Wang, P., et al.[2022]

Alectinib demonstrated significantly better efficacy than crizotinib in treating ALK-positive non-small cell lung cancer, with improved progression-free survival (PFS) and overall survival (OS) based on a pooled analysis of 697 patients from three clinical trials.

In terms of safety, alectinib had a lower incidence of severe adverse effects compared to crizotinib, which was associated with higher rates of gastrointestinal issues and other side effects, making alectinib a more favorable option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Crizotinib versus Alectinib for the Treatment of ALK-Positive Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis. Zeng, Q., Zhang, X., He, S., et al.[2022]

In a study of 61 patients with ALK-rearranged non-small cell lung cancer (NSCLC), alectinib treatment resulted in significantly better overall survival (OS), time to treatment failure (TTF), and progression-free survival (PFS) compared to crizotinib.

Sequential treatment with crizotinib followed by alectinib after crizotinib failure showed a trend towards improved OS compared to alectinib alone, suggesting that combining therapies may enhance treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential Therapy with Crizotinib and Alectinib in ALK-Rearranged Non-Small Cell Lung Cancer-A Multicenter Retrospective Study. Ito, K., Hataji, O., Kobayashi, H., et al.[2022]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Alectinib: A Review in Advanced, ALK-Positive NSCLC. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Alectinib for treatment of ALK-positive non-small-cell lung cancer. [2022]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Alectinib: a review of its use in advanced ALK-rearranged non-small cell lung cancer. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

The percentage of ALK-positive cells and the efficacy of first-line alectinib in advanced non-small cell lung cancer: is it a novel factor for stratification? (Turkish Oncology Group Study). [2023]

5. New Zealand pubmed.ncbi.nlm.nih.gov

The efficacy and safety of alectinib in the treatment of ALK+ NSCLC: a systematic review and meta-analysis. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Comparison of Clinical Efficacy of Alectinib Versus Crizotinib in ALK-Positive Non-Small Cell Lung Cancer: A Meta-Analysis. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of alectinib in a real-world surveillance study in patients with ALK-positive non-small-cell lung cancer in Japan. [2021]

8. Ireland pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes from the randomized phase III ALEX study of alectinib versus crizotinib in patients with ALK-positive non-small-cell lung cancer. [2020]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Alectinib Together with Intracranial Therapies Improved Survival Outcomes in Untreated ALK-Positive Patients with Non-Small-Cell Lung Cancer and Symptomatic and Synchronic Brain Metastases: A Retrospective Study. [2022]

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

Crizotinib versus Alectinib for the Treatment of ALK-Positive Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis. [2022]

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

Sequential Therapy with Crizotinib and Alectinib in ALK-Rearranged Non-Small Cell Lung Cancer-A Multicenter Retrospective Study. [2022]