Assess Efficacy and Safety of AZD6244 in Combination With Docetaxel in Patients Receiving Second Line Non Small Cell Lung Cancer Treatment.

NCT01750281 | Completed Phase 2 Results DMC

• 2 other identifiers: D1532C000642012-003622-25
• Study Type: interventional
• Target: 212
• Locations: 8 countries
• Sites: 68

Brief Summary

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 of docetaxel 75mg/m2 or 60 mg/m2 vs placebo and compare how well each dose affects how their cancer responds. It will also help us to understand the tolerability profile of the different dosing regimens in these patients

Conditions

Locally Advanced or Metastatic Non Small Cell Lung Cancer Stage IIIb - IV

Keywords

Mitogen-Activated Protein Kinase Kinase inhibitor; Non Small Cell Lung Cancer; Metastatic; Second line treatment for Non Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  Median time from randomisation until the date of objective disease progression or death (by any cause in the absence of progression). Progression is defined using Response Evaluation Criteria in Solid Tumours (RECIST v1.1): \>= 20% increase in the sum of diameters of Target Lesions (TL) and an absolute increase in sum of diameters of \>=5mm (compared to the previous minimum sum) or progression of Non TLs or a new lesion.

  Baseline and then every 6 weeks after randomization until objective disease progression, up to 29 months (at the time of the analysis)

Secondary Outcomes (1)

• Overall Survival (OS)

  Following progression, survival status was collected every 8 weeks until death, withdrawal of consent, or end of study, whichever occurred first, up to 29 months (at the time of the analysis)

Study Arms (3)

Selumetinib 75 mg twice daily +Docetaxel 75 mg/m2

EXPERIMENTAL

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.

Drug: Selumetinib 75 mg; Drug: Docetaxel 75 mg/m2

Selumetinib 75 mg twice daily + Docetaxel 60 mg/m2

EXPERIMENTAL

Selumetinib capsules will be administered orally uninterrupted twice daily in combination with docetaxel 60 mg/m2 intravenously administered on day 1 of each 21 day cycle.

Drug: Selumetinib 75 mg; Drug: Docetaxel 60 mg/m2

Placebo twice daily + Docetaxel 75 mg/m2

EXPERIMENTAL

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.

Drug: Docetaxel 75 mg/m2; Drug: Placebo

Interventions

Selumetinib 75 mg DRUG

Three selumetinib capsules (Hyd-Sulfate) 25 mg will be administered orally, twice daily, (75 mg dose bd) on an uninterrupted schedule.

Selumetinib 75 mg twice daily + Docetaxel 60 mg/m2; Selumetinib 75 mg twice daily +Docetaxel 75 mg/m2

Docetaxel 75 mg/m2 DRUG

Docetaxel 75 mg/m2 will be administered intravenously on day 1 of each 21 day cycle.

Placebo twice daily + Docetaxel 75 mg/m2; Selumetinib 75 mg twice daily +Docetaxel 75 mg/m2

Docetaxel 60 mg/m2 DRUG

Docetaxel 60 mg/m2 will be administered intravenously on day 1 of each 21 day cycle.

Selumetinib 75 mg twice daily + Docetaxel 60 mg/m2

Placebo DRUG

Three placebo capsules will be administered orally uninterrupted twice daily.

Placebo twice daily + Docetaxel 75 mg/m2

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed, written and dated informed consent prior to any study specific procedures
• Male or female, aged 18 years or older
• Histological or cytological confirmation of locally advanced or metastatic NSCLC (IIIB-IV)
• Prospective confirmation of KRAS mutation negative status as determined via an AZ approved laboratory
• Failure of 1st line anti-cancer therapy due to radiological documentation of disease progression in advanced disease or subsequent relapse of disease following 1st line therapy

You may not qualify if:

• Mixed small cell and non-small cell lung cancer histology
• Received \>1 prior anti-cancer drug regimen for advanced or metastatic NSCLC. Patients who develop disease progression while on switch maintenance therapy (maintenance using an agent not in the first-line regimen) will not be eligible.
• Other concomitant anti-cancer therapy agents except steroids
• Prior treatment with a MEK (Mitogen-Activated Protein Kinase) inhibitor or any docetaxel-containing regimen (prior treatment with paclitaxel is acceptable)
• The last radiation therapy within 4 weeks prior to starting study treatment, or limited field of radiation for palliation within 7 days of the first dose of study treatment.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (68)

Research Site

Santa Monica, California, 90404, United States

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Aurora, Colorado, 80045, United States

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Hollywood, Florida, 33028, United States

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Atlanta, Georgia, 30318, United States

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Chicago, Illinois, 60637, United States

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Marrero, Louisiana, 70072, United States

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Boston, Massachusetts, 02215, United States

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Mineola, New York, 11501, United States

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New York, New York, 10011, United States

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New York, New York, 10032, United States

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Hershey, Pennsylvania, 17033-0850, United States

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Philadelphia, Pennsylvania, 19107, United States

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Nashville, Tennessee, 37203, United States

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Barretos, 14784-400, Brazil

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Brasília, 70390-055, Brazil

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Ijuí, 98700-000, Brazil

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Porto Alegre, 90035-003, Brazil

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Porto Alegre, 90619-900, Brazil

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Porto Alegre, 91350-200, Brazil

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Santo André, 09060-650, Brazil

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São José do Rio Preto, 15090-000, Brazil

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São Paulo, 01221-020, Brazil

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São Paulo, 01246-000, Brazil

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São Paulo, 04039-002, Brazil

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Plovdiv, 4000, Bulgaria

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Plovdiv, 4004, Bulgaria

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Sofia, 1233, Bulgaria

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Sofia, 1303, Bulgaria

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Sofia, 1330, Bulgaria

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Sofia, 1756, Bulgaria

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Varna, 9010, Bulgaria

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Vratsa, 3000, Bulgaria

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Brest, 29609, France

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Caen, F-14033, France

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Clermont-Ferrand, 63003, France

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Lille, 59000, France

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Pierre-Bénite, 69310, France

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Villejuif, 94805, France

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Essen, 45122, Germany

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Esslingen am Neckar, 73730, Germany

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Großhansdorf, 22927, Germany

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Karlsruhe, 76137, Germany

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Löwenstein, 74245, Germany

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Moers, 47441, Germany

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Wiesbaden, 65199, Germany

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Würzburg, 97080, Germany

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Budapest, 1032, Hungary

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Budapest, 1121, Hungary

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Budapest, 1122, Hungary

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Edelény, 3780, Hungary

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Győr, 9024, Hungary

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Kaposvár, 7400, Hungary

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Miskolc, 3529, Hungary

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Nyíregyháza, 4400, Hungary

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Székesfehérvár, 8000, Hungary

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Törökbálint, 2045, Hungary

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's-Hertogenbosch, 5223 GZ, Netherlands

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Amsterdam, 1066 CX, Netherlands

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Amsterdam, 1081 HV, Netherlands

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Bergen op Zoom, 4624 VT, Netherlands

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Maastricht, 6202 AZ, Netherlands

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Gdansk, 80-219, Poland

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Grudziądz, 86-300, Poland

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Krakow, 31-202, Poland

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Olsztyn, 10-357, Poland

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Poznan, 61-848, Poland

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Sucha Beskidzka, 34-200, Poland

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Szczecin, 70-891, Poland

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Related Publications (1)

• Soria JC, Fulop A, Maciel C, Fischer JR, Girotto G, Lago S, Smit E, Ostoros G, Eberhardt WEE, Lishkovska P, Lovick S, Mariani G, McKeown A, Kilgour E, Smith P, Bowen K, Kohlmann A, Carlile DJ, Janne PA. 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. Ann Oncol. 2017 Dec 1;28(12):3028-3036. doi: 10.1093/annonc/mdx628.

  PMID: 29045535 DERIVED

Related Links

• CSR Synopsis Redacted

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Neoplasm Metastasis

Interventions

AZD 6244; Docetaxel

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Results Point of Contact

• Title: Dr Gabriella Mariani
• Organization: AstraZeneca

ClinicalTrialTransparency@astrazeneca.com

+44 (0)207 6048000

Study Officials

• Gabriella Mariani, MD

  AstraZeneca UK, MSD

  STUDY CHAIR

• Pasi Janne, MD

  Dana-Farber Cancer Institute, USA

  PRINCIPAL INVESTIGATOR

• Jean-Charles Soria, MD

  Institut de Cancerology Gustave Roussy, France

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2012
• First Posted: December 17, 2012
• Study Start: December 18, 2012
• Primary Completion: January 27, 2016
• Study Completion: October 31, 2022
• Last Updated: October 24, 2023
• Results First Posted: July 19, 2017

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

Locations

BR (11); FR (6); NL (5); DE (8); BU (8); US (13); PL (7); HU (10)