Selumetinib + Docetaxel for Lung Cancer

(SELECT-1 Trial)

Not currently recruiting at 199 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must not be taking: MEK inhibitors, Docetaxel

Disqualifiers: Small cell lung cancer, 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

Compensation: Varies

Number of Visits: 1

Duration: 21-day cycles, repeated until disease progression or unacceptable toxicity

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for certain types of lung cancer. It examines the effectiveness of selumetinib (a targeted therapy) combined with docetaxel (a chemotherapy drug) compared to a placebo with docetaxel in treating non-small cell lung cancer (NSCLC) that is either locally advanced or has spread and has a specific KRAS mutation. The trial also aims to assess the safety and patient experience while taking these drugs. Patients with a KRAS mutation in their lung cancer, whose cancer worsened after initial treatment, might be suitable candidates. As a Phase 3 trial, this study represents the final step before FDA approval, offering patients access to potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have received any systemic anti-cancer therapy within 30 days before starting the study treatment. It's best to discuss your current medications with the trial team.

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

Past studies have tested the combination of selumetinib and docetaxel for safety. Researchers found that most patients tolerated the treatment well. Some reported side effects included fatigue, nausea, and low blood cell counts, which are common with cancer treatments. Importantly, evidence suggested that these side effects can be managed, allowing doctors to help with symptoms if they occur. So far, the treatment appears to be as safe as other options used for lung cancer. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for lung cancer?

Researchers are excited about Selumetinib combined with Docetaxel for lung cancer because it introduces a new mechanism of action, targeting the MEK pathway, which plays a crucial role in cell growth and survival. Unlike standard treatments like chemotherapy alone, Selumetinib aims to enhance the effectiveness of Docetaxel by specifically inhibiting this pathway, potentially leading to better outcomes. Additionally, Selumetinib is administered orally, which could offer more convenience compared to some intravenous options. This novel approach could provide a fresh avenue for tackling lung cancer, sparking hope for improved patient responses.

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

In this trial, participants will receive either the combination of selumetinib and docetaxel or a placebo with docetaxel. Research has shown mixed results when adding selumetinib to docetaxel for treating advanced lung cancer with KRAS mutations. Some studies found that this combination did not significantly outperform docetaxel alone. Patients with this type of lung cancer did not experience a clear benefit from adding selumetinib. The aim of using selumetinib is to target specific cancer pathways affected by KRAS mutations, potentially enhancing the treatment's effectiveness against cancer. While there is hope for this combination, further research is needed to confirm its efficacy. ^{1 2 4 6 7}

Who Is on the Research Team?

Pasi Jänne, MD

Principal Investigator

Dana-Faber Cancer Institute, USA

Gabriella Mariani, MD

Principal Investigator

AstraZeneca UK, MSD

Are You a Good Fit for This Trial?

This trial is for adults over 18 with advanced or metastatic non-small cell lung cancer (NSCLC) that's KRAS mutation positive. They must have had one failed anti-cancer therapy but can't have had MEK inhibitors, docetaxel regimens, other recent cancer treatments, or certain types of radiation.

Inclusion Criteria

Provision of signed, written and dated informed consent prior to any study specific procedures

You have been diagnosed with advanced or metastatic non-small cell lung cancer.

You have a specific mutation called KRAS in your tumor.

Exclusion Criteria

Receiving or have received systemic anti-cancer therapy within 30 days prior to starting study treatment

Last radiation therapy within 4 weeks prior starting study treatment, or limited field of radiation for palliation within 7 days of the first dose of study treatment

You have a type of lung cancer that is a mix of small cell and non-small cell types.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Selumetinib or placebo in combination with Docetaxel every 21 days

21-day cycles, repeated until disease progression or unacceptable toxicity

1 visit every 21 days (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days post treatment discontinuation or progression

Long-term follow-up

Participants are monitored for overall survival and progression-free survival

Approximately 3.5 years after first subject in

What Are the Treatments Tested in This Trial?

Interventions

• Docetaxel
• Placebo
• Selumetinib

Trial Overview The study tests the effectiveness of Selumetinib combined with Docetaxel against a placebo plus Docetaxel in patients with KRAS mutated NSCLC. It will also evaluate how the body processes the drugs, their safety, and patient-reported outcomes.

How Is the Trial Designed?

Group I: Selumetinib + Docetaxel Experimental Treatment 3 Interventions

Three 25mg Selumetinib capsules will be administered orally uninterrupted twice daily in combination with docetaxel 75 mg/m2 intravenously administered on day 1 of each 21 day cycle

Group II: Placebo + Docetaxel Experimental Treatment 3 Interventions

Three placebo capsules will be administered orally uninterrupted twice daily in combination with docetaxel 75 mg/m2 intravenously administered on day 1 of each 21 day cycle.

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?

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

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]

In a study involving 441 patients with advanced non-small-cell lung cancer, both cisplatin/docetaxel and gemcitabine/docetaxel combinations showed similar efficacy, with objective response rates of 32.4% and 30.2%, respectively.

Gemcitabine/docetaxel demonstrated a more favorable toxicity profile compared to cisplatin/docetaxel, making it a potentially safer option for patients undergoing treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Platinum-based and non-platinum-based chemotherapy in advanced non-small-cell lung cancer: a randomised multicentre trial. Georgoulias, V., Papadakis, E., Alexopoulos, A., et al.[2022]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5834012/

SELECT-2: a phase II, double-blind, randomized, placebo ... The phase II SELECT-2 trial investigated safety and efficacy of selumetinib plus docetaxel for patients with advanced or metastatic NSCLC. Patients and methods.

2. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2625317

Selumetinib Plus Docetaxel Compared With ... Among patients with previously treated advanced KRAS-mutant NSCLC, addition of selumetinib to docetaxel did not provide benefit over docetaxel alone.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT01933932

Study Details | NCT01933932 | Assess Efficacy & Safety of ... The purpose of this study is to assess the efficacy of selumetinib in combination with docetaxel (75mg/m2) vs placebo in combination with docetaxel ...

4. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D1532C00079

Assess Efficacy & Safety of Selumetinib in Combination ... The purpose of this study is to assess the efficacy of selumetinib in combination with docetaxel (75mg/m2) vs placebo in combination with docetaxel ...

5. dana-farber.org dana-farber.org/clinical-trials/14-057

A Phase III, Double-Blind, Randomised, Placebo- ... The purpose of this study is to assess the efficacy of selumetinib in combination with docetaxel (75mg/m2) vs placebo in combination with docetaxel ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/29045535/

SELECT-2: a phase II, double-blind, randomized, placebo ... ... lung cancer (NSCLC). The phase II SELECT-2 trial investigated safety and efficacy of selumetinib plus docetaxel for patients with advanced or metastatic NSCLC.

7. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D1532C00064

Assess Efficacy and Safety of AZD6244 in Combination ... The purpose of this study is to treat patients with locally advanced or metastatic NSCLC with a combination therapy of selumetinib and two different doses ...