Assess Safety & Efficacy of Selumetinib When Given in Combination With Standard First Line Treatment for Advanced Non-small Cell Lung Cancer

NCT01809210 | Completed Phase 1 Results

• 2 other identifiers: D1532C00070EudraCT number: 2012-005202-22
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 4

Brief Summary

This is a Phase I, open label multicentre study of selumetinib administered orally in combination with first line chemotherapy regimens to patients with advanced/metastatic NSCLC. The study has been designed to allow an investigation of the optimal dose of selumetinib in combination with various standard first line double-platinum chemotherapy regimens. Initial assessment will be based on tolerability of selumetinib in combination with one or more selected regimens that are considered to be tolerated also being assessed for preliminary evidence of activity. This study is a dose finding and optional cohort expansion; In addition all patients will be assessed for anti-cancer efficacy of the combination of selumetinib and chemotherapy.

Conditions

Locally Advanced or Metastatic NSCL Cancer Stage IIIB IV

Keywords

MEK1/2 inhibitor,; Non Small Cell Lung Cancer,; metastatic,; first line treatment for Non Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Dose Limiting Toxicity (DLT) Events in Chemotherapy in Combination With Selumetinib

  Any toxicity not attributable to the disease or disease-related processess under investigation, considered related to the combination of chemotherapy plus selumetinib, which occurs within the timeframe and is dose limiting

  The first dose on Cycle 1 Day 1 up to the time before dosing on Cycle 2 Day 1, assessed up to 3 weeks

Secondary Outcomes (8)

• Best Objective Response

  Screening, week 6 and week 12

• Percentage Change From Baseline at 6 Weeks in Target Lesion Size

  Week 6

• Best Percentage Change From Baseline in Target Lesion Size

  Screening, week 6 and week 12

• Objective Response Rate (ORR)

  Up until progression or last evaluable assessment in the absence of progression, up to 9 months

• AUC (0-tau)

  Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose

Study Arms (1)

Selumetinib+standard chemotherapy

EXPERIMENTAL

Selumetinib plus gemcitabine; or pemetrexed and cisplatin or carboplatin

Drug: selumetinib; Drug: gemcitabine; Drug: cisplatin; Drug: carboplatin; Drug: pemetrexed

Interventions

selumetinib DRUG

2 x 25mg capsules bd continuously in cohort 1 (with gemcitabine and cisplatin). If tolerated - next cohort 3 x 25mg capsules bd continuously. if higher doses are explored, required number of capsules will be provided. Option to administer on D2-19 of each 21 day cycle if required to assess tolerability of combinations with chemotherapy

Selumetinib+standard chemotherapy

gemcitabine DRUG

1250 mg/m2 iv on Day 1 and 8 of each 21 day cycle. If combination not tolerated, option to give 1000 mg/m2 iv on Day 1 and Day 8 of each 21 day cycle

Selumetinib+standard chemotherapy

cisplatin DRUG

75 mg/m2 iv on Day 1 of each 21 day cycle. If combination not tolerated, option to give 50 mg/m2 iv on Day 1 or 25mg/m2 iv on Day 1 and Day 8 of each 21 day cycle

Selumetinib+standard chemotherapy

carboplatin DRUG

If it is not possible to identify a tolerable combination of selumetinib, gemcitabine and cisplatin, cisplatin may be replaced with carboplatin (AUC5) iv on Day 1 of each 21 day cycle

Selumetinib+standard chemotherapy

pemetrexed DRUG

Gemcitabine may be replaced with pemetrexed 500 mg/m2 iv on Day 1 of each 21 day cycle.

Selumetinib+standard chemotherapy

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed, written and dated 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)
• Female patients must not be breast-feeding and have a negative pregnancy test prior to start of dosing or must have evidence of non-child-bearing potential
• Patients must be eligible to receive treatment with the platinum doublet combination with which selumetinib is being combined and in accordance with the local product information

You may not qualify if:

• Prior chemotherapy or other systemic anti-cancer treatment for advanced NSCLC.
• Prior surgery or radiotherapy within 6 months or palliative radiotherapy within 4 weeks of start of study treatment.
• Female patients who are breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control
• Another primary malignancy within 5 years of starting study treatment, except for adequately treated basal or squamous cell carcinoma of the skin or cancer of the cervix in situ.
• As judged by the Investigator, any evidence of severe or uncontrolled systemic diseases, active bleeding diatheses, renal transplant, or active infection

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (4)

Research Site

Glasgow, G12 0YN, United Kingdom

Location

Research Site

London, W1G 6AD, United Kingdom

Location

Research Site

Manchester, M20 4BX, United Kingdom

Location

Research Site

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

Related Links

• D1532C00070revisedCSP-2\_Redacted

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Neoplasm Metastasis

Interventions

AZD 6244; Gemcitabine; Cisplatin; Carboplatin; Pemetrexed

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)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Results Point of Contact

• Title: Dr Gabriella Mariani , MD
• Organization: AstraZeneca

ClinicalTrialTransparency@astrazeneca.com

+44 (0)207 6048000

Study Officials

• Gabriella Mariani, MD

  AstraZeneca UK, MSD

  STUDY DIRECTOR

• Emma Dean, BMEDSCI, BM, BS, PHD

  The Christie NHS Foundation Trust, UK

  PRINCIPAL INVESTIGATOR

• Fiona Blackhall, PhD, FRCP

  The Christie NHS Foundation Trust Clinical Trials Unit; UK

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2013
• First Posted: March 12, 2013
• Study Start: April 4, 2013
• Primary Completion: January 4, 2016
• Study Completion: January 4, 2016
• Last Updated: March 13, 2018
• Results First Posted: March 13, 2018

Record last verified: 2018-03

Locations

GB (4)