Ceritinib + Docetaxel for Lung Cancer

Not currently recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must not be taking: QT prolonging, CYP3A4/5, Warfarin, others

Disqualifiers: ALK, EGFR, Active malignancies, others

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

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate how a combination of two medications, ceritinib (a targeted therapy) and docetaxel (a chemotherapy drug), affects individuals with advanced non-small cell lung cancer (NSCLC). Researchers seek to identify the safest dose of these drugs and assess their potential in combating this type of lung cancer. The study will include several groups to test different dose levels to determine the optimal one. Individuals with advanced NSCLC who have undergone 1-3 previous treatments and are willing to provide a tumor sample may be suitable candidates for this trial.

As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications at least 1 week before starting the study. These include medications that affect heart rhythm, certain enzyme inhibitors or inducers, some anticoagulants, specific anticonvulsants, and herbal medications.

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

Research has shown that ceritinib, compared to chemotherapy, carries some risks. In one study, out of 15 patients who died while taking ceritinib, two deaths were linked to unexpected medical problems. This indicates that while ceritinib can be effective, it may also have serious side effects for some individuals.

The combination of ceritinib with docetaxel, a chemotherapy drug, remains under investigation. This combination might be more effective for certain types of lung cancer. However, as this is an early-stage trial, the safety of using these two drugs together is not fully understood. The trial aims to determine a safe dose, meaning researchers are still assessing how well patients can tolerate the combination. Participants should be aware of the potential risks and benefits and discuss them with their doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of ceritinib and docetaxel for lung cancer because it targets cancer cells in a novel way. While standard treatments like chemotherapy attack all rapidly dividing cells, ceritinib is a targeted therapy that specifically inhibits the ALK (anaplastic lymphoma kinase) gene, which can drive tumor growth in certain lung cancers. This targeted action, combined with docetaxel's ability to disrupt cell division, could offer a more effective approach with potentially fewer side effects compared to traditional chemotherapy alone. By potentially enhancing the precision and effectiveness of treatment, this combination holds promise for improving outcomes in patients with lung cancer.

What evidence suggests that this combination of ceritinib and docetaxel could be effective for lung cancer?

Research has shown that ceritinib may help treat non-small cell lung cancer (NSCLC), particularly in patients with ALK-positive mutations. Patients taking 450 mg of ceritinib experienced a median progression-free survival (PFS) of 7 months, during which their cancer did not grow or spread. Ceritinib proves more effective when taken with food, enhancing patient outcomes.

Docetaxel is another treatment for NSCLC with positive results. Studies have found that patients experienced relief from symptoms like cough and pain after using this treatment. The median survival time for those treated with docetaxel was about 11 months, aiding in disease control. In this trial, participants will receive varying doses of ceritinib combined with docetaxel to determine the maximum tolerated dose. Together, these drugs could offer a promising treatment option for NSCLC. ^{6 7 8 9 10}

Who Is on the Research Team?

Andreas Saltos, MD

Principal Investigator

H. Lee Moffitt Cancer Center and Research Institute

Are You a Good Fit for This Trial?

Adults over 18 with advanced/metastatic Non-small Cell Lung Cancer (NSCLC) who've had up to three prior treatments, including a platinum-based agent and possibly one PD-1 or PD-L1 antibody regimen. They must have treated brain metastases if present, be able to provide recent tumor tissue samples, and not be pregnant while using contraception. Excluded are those with ALK rearrangements, EGFR mutations, other active cancers at high relapse risk, major surgery recovery within the last month, uncontrolled medical conditions or allergies to trial drugs.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

If you had brain metastases before, you can join if: they were treated, you don't have symptoms, you stopped taking corticosteroids for them at least 7 days ago, they are not getting worse, and you meet other health requirements. If you can become pregnant, you must use birth control.

Ability to understand and provide informed consent

Exclusion Criteria

Serious uncontrolled medical disorder, psychiatric condition or laboratory abnormalities that, in the opinion of the investigator, may increase the risk associated with study participation or may interfere with the interpretation of study results

I am allergic to ceritinib, docetaxel, or their ingredients.

I haven't had major surgery in the last 4 weeks or still have side effects.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I Dose Escalation

Participants receive escalating doses of ceritinib and docetaxel to determine the maximum tolerated dose

Up to 6 months

Phase Ib Dose Expansion

Participants receive treatment at the recommended dose to evaluate overall response

Up to 30 months

Follow-up

Participants are monitored for progression-free survival and overall survival

Up to 30 months

What Are the Treatments Tested in This Trial?

Interventions

• Ceritinib
• Docetaxel

Trial Overview The trial is testing the combination of Ceritinib (Zykadia®) and Docetaxel (Taxotere®) on participants with NSCLC. The goal is to determine the safest dose that can effectively treat this cancer type by observing both positive effects and any adverse reactions from this drug duo.

How Is the Trial Designed?

Group I: Phase Ib Dose Expansion Experimental Treatment 2 Interventions

Treatment at recommended dose. Investigators plan to have 30 patients for the expansion cohort. This will include participants from the dose escalation portion receiving the recommended dose.

Group II: Phase I Dose Escalation Experimental Treatment 2 Interventions

The design will recruit participants in cohorts of three patients each and will not allow for dose-skipping during escalation. A maximum of 18 participants will be enrolled for the phase I dose escalation. Three ceritinib dose levels have been identified for dose escalation (150 mg, 300 mg, and 450 mg), plus docetaxel at 75 mg. A backup dose (ceritinib 150 mg with docetaxel at 60 mg) is also prepared in case the three dose levels are too toxic. Therefore, four potential dose levels will be used for determination of maximum tolerated dose (MTD). The first cohort will start at dose level 1 (ceritinib 150 mg with docetaxel at 75 mg). Level -1 Backup Cohort: 150 mg ceritinib; 60 mg/m\^2 docetaxel Level 1 Starting Cohort: 150 mg ceritinib; 75 mg/m\^2 docetaxel Level 2 Cohort: 300 mg ceritinib; 75 mg/m\^2 docetaxel Level 3 Cohort: 450 mg ceritinib; 75 mg/m\^2 docetaxel

Ceritinib is already approved in United States for the following indications:

Approved in United States as Danyelza for:

• High-risk neuroblastoma in the bone or bone marrow

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

Published Research Related to This Trial

Docetaxel is an effective treatment for non-small cell lung cancer (NSCLC), showing comparable efficacy to newer platinum-based therapies in advanced stages, and has been approved for use in this context.

Clinical trials are ongoing to explore the best ways to combine docetaxel with other treatments, such as thoracic radiotherapy and molecularly targeted agents, to enhance its effectiveness in various stages of NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel in non-small cell lung cancer: a review. Davies, AM., Lara, PN., Mack, PC., et al.[2019]

In a phase 2 study involving 80 chemotherapy-naïve patients with advanced nonsmall cell lung cancer (NSCLC), the combination of cetuximab, carboplatin, and docetaxel showed a modest objective response rate of 15.2% and a median overall survival of 10.3 months.

The treatment was generally well tolerated, with significant adverse events including neutropenia (30%), but patients who continued on single-agent cetuximab after initial treatment experienced manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab in combination with carboplatin and docetaxel for patients with metastatic or advanced-stage nonsmall cell lung cancer: a multicenter phase 2 study. Belani, CP., Schreeder, MT., Steis, RG., et al.[2019]

Docetaxel is an effective treatment for advanced non-small cell lung cancer (NSCLC), showing survival benefits in both first- and second-line therapy, and is comparable or superior to other platinum-based chemotherapy options.

The drug has a manageable toxicity profile and has shown promising results when combined with novel targeted agents in Phase II studies, indicating its versatility in treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel in advanced non-small cell lung cancer. Wakelee, H., Ramalingam, S., Belani, CP.[2018]

Docetaxel is a highly effective treatment for advanced non-small-cell lung cancer (NSCLC), showing improved patient quality of life compared to vinorelbine-cisplatin in clinical trials, leading to its FDA approval for this indication.

With a higher binding affinity for beta tubulin than paclitaxel, docetaxel is the only chemotherapy agent approved for both first- and second-line therapy of advanced NSCLC, demonstrating its versatility and efficacy in various treatment settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of docetaxel in advanced non-small-cell lung cancer. Belani, CP., Eckardt, J.[2022]

In a study of 170 patients with advanced non-small cell lung cancer, those treated with EGFR-TKIs as second-line therapy showed the highest response rate (36.1%) and the longest progression-free survival (PFS) of 9.31 months, compared to 15.0% response rate and 5.49 months PFS for docetaxel and 24.5% response rate and 5.42 months PFS for pemetrexed.

All three treatments (docetaxel, pemetrexed, and EGFR-TKIs) had comparable safety profiles, but there was no significant difference in median survival time (MST) among the groups, indicating that while EGFR-TKIs may offer better short-term benefits, long-term survival outcomes were similar across treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and safety of docetaxol, pemetrexed and EGFR-TKIs as second-line treatment for patients with advanced non-small-cell lung cancer]. Zhang, RX., Cai, DY., Wu, XH., et al.[2018]

Citations

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Efficacy of Crizotinib, Ceritinib, and Alectinib in ALK-Positive ... This study aimed to evaluate the efficacy of anaplastic lymphoma kinase (ALK)-inhibitors in the treatment of ALK-positive non-small cell lung cancer (NSCLC) ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa1311107

Ceritinib in ALK-Rearranged Non–Small-Cell Lung Cancer Among patients with NSCLC who received at least 400 mg of ceritinib per day, the median progression-free survival was 7.0 months (95% CI, 5.6 to ...

3. journals.lww.com journals.lww.com/cancerjournal/fulltext/2022/18020/clinical_data_from_the_real_world__efficacy.28.aspx

Clinical data from the real world: Efficacy analysis of... Ceritinib administered at 450 mg QD to ALK-rearrangement NSCLC patients with BM in China exhibited superior ORR and DCR, as well as PFS and event free ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02393625

NCT02393625 | Study of Safety and Efficacy of Ceritinib in ... This is an open label multi center trial to determine the safety and efficacy of ceritinib in combination with nivolumab in ALK-positive NSCLC patients.

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ASCEND-8 pharmacokinetic, safety, and efficacy data for ... Prescribing ceritinib 450 mg with food may positively impact patient management. Abstract. Anaplastic lymphoma kinase–positive (ALK+) non-small cell lung cancer ...

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Ceritinib versus chemotherapy in patients with ALK ... 13 (87%) of the 15 patients who died in the ceritinib group died because of disease progression and two (13%) died because of an adverse event (one [7%] ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03611738

Ceritinib Plus Docetaxel in ALK-Negative, EGFR WT ... Study rationale is that targeting ALK- and EGFR-negative lung tumors with ceritinib and microtubule inhibitors results in synergistic antitumor effects.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5892855/

Phase 3 study of ceritinib vs chemotherapy in ALK ... In randomized, global, Phase 3 trial, ceritinib demonstrated a statistically significant and clinically meaningful improvement in PFS vs chemotherapy in ...

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S147020451730339X

Articles Ceritinib versus chemotherapy in patients with ALK ... In this study, we compared the efficacy and safety of ceritinib versus single-agent chemotherapy in patients with advanced ALK-rearranged non-small-cell lung ...

10. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30339-X/abstract

Ceritinib versus chemotherapy in patients with ALK ... In this study, we compared the efficacy and safety of ceritinib versus single-agent chemotherapy in patients with advanced ALK-rearranged non- ...