Ceritinib + Docetaxel for Lung Cancer

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

21 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The main purpose of this study is to find out what effects (good and bad) ceritinib (Zykadia®) used in combination with docetaxel (Taxotere®) will have on participants and their cancer. The results will help to determine the best safe dose of the combination of the medications Ceritinib (Zykadia®) and docetaxel (Taxotere®) and to find out if this combination of drugs will help people that have this type of Non-small Cell Lung Cancer (NSCLC).

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.

What safety data exists for Docetaxel in lung cancer treatment?

Docetaxel has been studied in various combinations for treating advanced non-small cell lung cancer and generally has a manageable safety profile. Common side effects include fatigue, nausea, and rash, but serious side effects are rare. ^{1 2 3 4 5}

What makes the drug combination of Ceritinib and Docetaxel unique for lung cancer treatment?

The combination of Ceritinib and Docetaxel for lung cancer is unique because Ceritinib is a targeted therapy that specifically inhibits ALK (anaplastic lymphoma kinase) mutations, which are present in some lung cancers, while Docetaxel is a chemotherapy drug that disrupts cell division. This combination may offer a novel approach by targeting cancer cells more precisely and effectively than standard chemotherapy alone. ^{1 4 5 6 7}

What data supports the effectiveness of the drug combination Ceritinib and Docetaxel for lung cancer?

Research shows that docetaxel, when used with other drugs like cetuximab, has been effective in treating advanced non-small cell lung cancer, suggesting potential benefits when combined with other treatments like Ceritinib. ^{1 4 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

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

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 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

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]

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]

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 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]

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]

Citations

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

A phase 2 study of cetuximab in combination with docetaxel in chemotherapy-refractory/resistant patients with advanced nonsmall cell lung cancer. [2021]

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

Quality of life and disease-related symptoms in previously treated Japanese patients with non-small-cell lung cancer: results of a randomized phase III study (V-15-32) of gefitinib versus docetaxel. [2022]

3. United States 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. [2019]

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

Immunotherapy in Lung Cancer. [2022]

5. China 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]. [2018]

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

SELECT-2: a phase II, double-blind, randomized, placebo-controlled study to assess the efficacy of selumetinib plus docetaxel as a second-line treatment of patients with advanced or metastatic non-small-cell lung cancer. [2022]

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

A pilot trial of gefitinib in combination with docetaxel in patients with locally advanced or metastatic non-small-cell lung cancer. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Docetaxel in advanced non-small cell lung cancer. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Docetaxel in non-small cell lung cancer: a review. [2019]

10. Ireland pubmed.ncbi.nlm.nih.gov

Development of docetaxel in advanced non-small-cell lung cancer. [2022]