Selumetinib + Docetaxel for Lung Cancer

(SELECT-1 Trial)

Recruiting at 165 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

510 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to assess the efficacy of selumetinib in combination with docetaxel (75mg/m2) vs placebo in combination with docetaxel (75mg/m2) in patients with locally advance or metastatic NSCLCs that harbor mutations of KRAS. This study will also assess the PK, safety, patient reported outcomes (PRO) and tolerability profile of the selumetinib/docetaxel combination, compared to placebo in combination with docetaxel

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.

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

Research shows that combining Selumetinib with Docetaxel improves survival rates and response to treatment in patients with advanced non-small-cell lung cancer, especially those with specific genetic mutations (KRAS mutant). ^{1 2 3 4 5}

Is the combination of Selumetinib and Docetaxel safe for humans?

The combination of Selumetinib and Docetaxel has been studied for safety in patients with advanced non-small-cell lung cancer, showing it is generally safe and tolerable. These studies included different patient groups, such as Japanese patients, and found the treatment to be manageable in terms of side effects. ^{1 2 4 6 7}

How is the drug combination of Selumetinib and Docetaxel unique for treating lung cancer?

The combination of Selumetinib and Docetaxel is unique because it targets KRAS-mutant advanced non-small-cell lung cancer (NSCLC), providing clinical benefits as a second-line treatment, which is not commonly addressed by other standard therapies. ^{2 4 7 8 9}

Research Team

Pasi Jänne, MD

Principal Investigator

Dana-Faber Cancer Institute, USA

Gabriella Mariani, MD

Principal Investigator

AstraZeneca UK, MSD

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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

Impact of KRAS codon subtypes from a randomised phase II trial of selumetinib plus docetaxel in KRAS mutant advanced non-small-cell lung cancer. [2018]

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

Safety and tolerability of selumetinib as a monotherapy, or in combination with docetaxel as second-line therapy, in Japanese patients with advanced solid malignancies or non-small cell lung cancer. [2022]

3. England pubmed.ncbi.nlm.nih.gov

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

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

Platinum-based and non-platinum-based chemotherapy in advanced non-small-cell lung cancer: a randomised multicentre trial. [2022]

5. 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]

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

A multicenter phase II study of the efficacy and safety of docetaxel plus cisplatin in Asian chemonaïve patients with metastatic or locally advanced non-small cell lung cancer. [2019]

7. 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]

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

Phase II study of docetaxel and cisplatin in advanced non-small-cell lung cancer. [2018]

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

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