Trametinib + Docetaxel for Non-Small Cell Lung Cancer

Recruiting at 694 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Herbal supplements

Disqualifiers: Brain metastases, Interstitial lung 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: Unknown

Duration: 21 days per cycle

60 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well trametinib and docetaxel work in treating patients with stage IV KRAS mutation positive non-small cell lung cancer or cancer that has come back. Trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving trametinib with docetaxel may work better in treating non-small cell lung cancer.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but it does prohibit the use of all herbal supplements during the study. It's best to discuss your current medications with the study team to ensure they don't interfere with the trial treatments.

What data supports the effectiveness of the drug combination Trametinib and Docetaxel for treating non-small cell lung cancer?

Docetaxel has been shown to improve survival rates in patients with advanced non-small cell lung cancer (NSCLC) when used alone or in combination with other drugs, and it is approved for both first- and second-line treatment of NSCLC. While specific data on the combination of Trametinib and Docetaxel is not provided, Docetaxel's effectiveness in NSCLC treatment is well-documented. ^{1 2 3 4 5}

Is the combination of Trametinib and Docetaxel safe for humans?

Docetaxel, one of the drugs in the combination, is generally safe for humans but can cause severe neutropenia (a drop in white blood cells that fight infection) as a major side effect. It has been used safely in treating various cancers, including lung cancer, but the specific combination with Trametinib hasn't been detailed in the provided studies. ^{6 7 8 9 10}

What makes the drug combination of Trametinib and Docetaxel unique for treating non-small cell lung cancer?

The combination of Trametinib and Docetaxel is unique because Trametinib, a MEK inhibitor, targets a specific pathway involved in cancer cell growth, while Docetaxel, a chemotherapy drug, disrupts cell division. This dual approach may offer a novel mechanism of action compared to standard treatments that typically involve only chemotherapy agents. ^{1 2 4 11 12}

Research Team

Shirish M Gadgeel

Principal Investigator

SWOG Cancer Research Network

Eligibility Criteria

This trial is for adults with stage IV or recurrent non-small cell lung cancer (NSCLC) that has a specific KRAS mutation. Participants must not have brain metastases unless treated and stable, no recent chemotherapy or investigational drugs, normal organ function tests, no history of significant heart disease or interstitial lung disease, and cannot be pregnant. They should not have had certain prior treatments like MEK inhibitors.

Inclusion Criteria

I've had radiation that didn't affect more than 25% of my bone marrow and have recovered from its side effects.

I am not taking any herbal supplements.

Your hemoglobin level is at least 9 grams/dl, and this was checked within the last 28 days before joining the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive trametinib orally on days 1-21 and docetaxel intravenously on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

21 days per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment completion every 6 months for 3 years.

3 years

Treatment Details

Interventions

• Docetaxel
• Trametinib

Trial Overview The study is testing the combination of trametinib, which blocks enzymes needed for tumor growth, and docetaxel, a chemotherapy drug that kills or stops cancer cells from dividing. The goal is to see if this combo works better than current treatments for NSCLC with KRAS mutations.

Participant Groups

Group I: Treatment (trametinib, docetaxel) Experimental Treatment 3 Interventions

Patients receive trametinib PO on days 1-21. Patients also receive docetaxel IV on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

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

Approved in United States as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in European Union as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in Canada as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in Japan as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

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]

The introduction of new chemotherapy agents, particularly taxanes like docetaxel, has significantly improved response rates in advanced non-small cell lung carcinoma (NSCLC) from 15-20% to 25-35%, along with median survival rates increasing to 8-10 months.

Docetaxel, especially when used alone or in combination with platinols, has become a standard treatment option for NSCLC, showing promising results in both treatment-naive and previously treated patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advanced non-small cell lung carcinoma: the emerging role of docetaxel. Langer, CJ.[2019]

Docetaxel is an effective treatment for advanced non-small cell lung cancer (NSCLC), showing improved overall survival compared to best supportive care in both first- and second-line therapies, based on randomized trials.

When combined with gemcitabine, docetaxel resulted in similar efficacy to combinations with cisplatin but caused significantly fewer severe side effects, making it a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The current status of docetaxel for advanced non-small cell lung cancer. Green, MR.[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]

The combination of docetaxel and cisplatin was found to be feasible and manageable at maximum-tolerated doses of docetaxel 100 mg/m2 and cisplatin 75 mg/m2, with a high median relative dose-intensity allowing for 81% of cycles to be administered at full dose.

Common side effects included severe leukocytopenia and granulocytopenia, but these were short-lasting and dose-dependent, while non-hematologic toxicities were generally mild to moderate, indicating a manageable safety profile for this chemotherapy regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I and pharmacologic study of docetaxel and cisplatin in patients with advanced solid tumors. Pronk, LC., Schellens, JH., Planting, AS., et al.[2018]

In a phase I trial involving 27 patients with advanced refractory cancer, the combination of sorafenib and docetaxel showed significant alterations in the pharmacokinetics of docetaxel, with increases in both the area under the concentration-time curve (AUC) and maximum concentration (Cmax).

The treatment was associated with a high incidence of adverse events, particularly dermatologic issues, leading to dose adjustments; however, 11% of patients experienced partial responses and 52% had stable disease, suggesting some efficacy in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial to investigate the safety, pharmacokinetics and efficacy of sorafenib combined with docetaxel in patients with advanced refractory solid tumours. Awada, A., Hendlisz, A., Christensen, O., et al.[2018]

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 chemotherapy drug that works by binding to microtubules, leading to cell-cycle arrest and apoptosis, and is approved for various cancers including breast, lung, prostate, and recently advanced gastric cancer.

While docetaxel can cause severe neutropenia as a major side effect, alternative dosing schedules have been developed to reduce this toxicity, making it safer for patients with compromised bone marrow.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel: a tubulin-stabilizing agent approved for the management of several solid tumors. Ramaswamy, B., Puhalla, S.[2018]

Docetaxel, when combined with other agents like cisplatin and gemcitabine, shows promising response rates (up to 53%) and median survival times (8 to 13 months) in patients with non-small-cell lung cancer, based on multiple phase I and II trials.

The combinations of docetaxel with other treatments have manageable adverse effects, making them a viable option for patients, with ongoing phase III trials to further evaluate their effectiveness in first-line treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel (Taxotere) in combination chemotherapy and in association with thoracic radiotherapy for the treatment of non-small-cell lung cancer. Thoracic Oncology Program. Ornstein, DL., Nervi, AM., Rigas, JR.[2022]

Docetaxel is recognized as one of the most effective cytotoxic drugs for treating non-small cell lung cancer, with ongoing clinical investigations exploring its use in combination therapies and radiotherapy.

Current studies at our hospital include trials combining docetaxel with gemcitabine and ifosfamide, as well as a planned randomized study to evaluate its effectiveness in conjunction with chemoradiotherapy for patients with inoperable stage III non-small cell lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel (Taxotere) in non-small cell lung cancer: ongoing studies in Heidelberg and future plans. Manegold, C.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

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

2. Ireland pubmed.ncbi.nlm.nih.gov

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

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

Advanced non-small cell lung carcinoma: the emerging role of docetaxel. [2019]

4. England pubmed.ncbi.nlm.nih.gov

The current status of docetaxel for advanced non-small cell lung cancer. [2018]

5. England pubmed.ncbi.nlm.nih.gov

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

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

Phase I and pharmacologic study of docetaxel and cisplatin in patients with advanced solid tumors. [2018]

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

Phase I trial to investigate the safety, pharmacokinetics and efficacy of sorafenib combined with docetaxel in patients with advanced refractory solid tumours. [2018]

8. 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]

9. Spain pubmed.ncbi.nlm.nih.gov

Docetaxel: a tubulin-stabilizing agent approved for the management of several solid tumors. [2018]

10. Greece pubmed.ncbi.nlm.nih.gov

Weekly docetaxel as second-line chemotherapy in advanced non-small cell lung cancer: phase II trial. [2018]

11. England pubmed.ncbi.nlm.nih.gov

Docetaxel (Taxotere) in combination chemotherapy and in association with thoracic radiotherapy for the treatment of non-small-cell lung cancer. Thoracic Oncology Program. [2022]

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

Docetaxel (Taxotere) in non-small cell lung cancer: ongoing studies in Heidelberg and future plans. [2022]