Study of Selumetinib in Patients With Previously Treated or Untreated Advanced/Metastatic NSCLC

NCT01783197 | Completed Phase 1 DMC

• 1 other identifier: I215
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 4

Brief Summary

This research is being done because further research on selumetinib in combination with standard chemotherapy treatment is needed. Although the number of treatment options for patients with advanced non-small cell lung cancer has increased over the past decade, prognosis remains poor, and there is a need for additional therapeutic options.

Conditions

Non Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Maximum dose tolerability of Selumetinib in patients

  Determination of the maximum administered dose and the recommended phase II dose

  24 months

Secondary Outcomes (1)

• Pharmacokinetic response prediction to selumetinib

  24 months

Study Arms (3)

Paclitaxel and carboplain plus selumetinib

EXPERIMENTAL

Cohort 1: Standard Chemotherapy (paclitaxel and carboplatin) plus selumetinib If you are registered to Cohort 1, you will receive two commonly-used chemotherapy drugs called paclitaxel and carboplatin, plus you will be given the experimental drug selumetinib.

Drug: Paclitaxel; Drug: Carboplatin; Drug: Selumetinib

pemetrexed and cisplain plus selumetinib

EXPERIMENTAL

Cohort 2: Standard Chemotherapy (pemetrexed and cisplatin) plus selumetinib (cohort closed) If you are registered to Cohort 2, you will receive two commonly-used chemotherapy drugs called pemetrexed and cisplatin, plus you will be given the experimental drug selumetinib.

Drug: Selumetinib; Drug: Pemetrexed; Drug: Cisplatin

pemetrexed plus selumetinib

EXPERIMENTAL

Cohort 3: Standard Chemotherapy (pemetrexed) plus selumetinib (cohort closed) If you are registered to Cohort 3, you will receive one commonly-used chemotherapy drug called pemetrexed, plus you will be given the experimental drug selumetinib.

Drug: Selumetinib; Drug: Pemetrexed

Interventions

Paclitaxel DRUG

Paclitaxel and carboplain plus selumetinib

Carboplatin DRUG

Paclitaxel and carboplain plus selumetinib

Selumetinib DRUG

Paclitaxel and carboplain plus selumetinib; pemetrexed and cisplain plus selumetinib; pemetrexed plus selumetinib

Pemetrexed DRUG

pemetrexed and cisplain plus selumetinib; pemetrexed plus selumetinib

Cisplatin DRUG

pemetrexed and cisplain plus selumetinib

Eligibility Criteria

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

You may qualify if:

• Histologically and/or cytologically confirmed NSCLC that is metastatic or unresectable and for which standard curative measures do not exist.
• All patients must have a formalin fixed paraffin embedded tissue block (from primary or metastatic tumour) available for correlative studies and must have provided informed consent for the release of the block as well as for blood samples for correlative studies.
• Although KRAS mutation is not mandatory, patients accrued to the RP2D expansion cohorts will have a sample sent for KRAS screening; patients must also have at least one site of disease which is unidimensionally measurable.
• Measurable disease defined as at least one target lesion that has not been irradiated and can be accurately measured in at least one dimension by RECIST 1.1 criteria.
• Chest X-ray ≥ 20 mm
• CT/MRI scan (with slice thickness of \< 5 mm) ≥ 10 mm --\> longest diameter
• Physical exam (using calipers) ≥ 10 mm
• Lymph nodes by CT scan ≥ 15 mm --\> measured in short axis
• Presence of clinically and/or radiologically documented disease (marker positive only patients are not eligible).
• All radiology studies must be performed within 28 days prior to registration (within 35 days if negative).
• Age \> 18 years.
• ECOG performance status 0 or 1
• Patients must have a life expectancy of at least 12 weeks.
• Previous Therapy
• Surgery:

You may not qualify if:

• Patients of Asian ethnicity are not eligible for the dose escalation phase of the study. Asian patients may be enrolled in the RP2D following informed consent and at the investigators discretion.
• Patients with a history of other untreated malignancies or malignancies which required therapy within the past 2 years.
• Patients with documented brain metastasis or carcinomatous meningitis, treated or untreated.
• Patients with significant cardiac disease, including:
• any factors that increase the risk of QTc prolongation or risk of arrhythmic events (e.g. heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age) or mean resting corrected QT interval (QTc) \> 470 msec
• uncontrolled hypertension (BP ≥ 150/95 mmHg despite medical therapy)
• acute coronary syndrome within 6 months prior to starting treatment
• angina Canadian Cardiovascular Society Grade II-IV (despite medical therapy)
• symptomatic heart failure (NYHA II-IV)
• prior or current cardiomyopathy
• atrial fibrillation with a ventricular rate \> 100bpm at rest
• severe valvular heart disease
• Patients who have neuropathy \> grade 1 or other conditions precluding treatment with the standard chemotherapy regimen planned.
• Patients who have significant gastrointestinal disease and who are unable to swallow capsules.
• Patients on potent inhibitors or inducers of CYP3A4/5, CYP2C19 and CYP1A2 (must have discontinued within 2 weeks prior to registration (3 weeks for St. John's Wort). Patients who do not agree to avoid the ingestion of large amounts of grapefruit and Seville oranges (and other products containing these fruits, e.g. grapefruit juice or marmalade). Participants who are taking supplemental vitamin E, that cannot be discontinued, are not eligible for the study.

Sponsors & Collaborators

• Canadian Cancer Trials Group: lead
• AstraZeneca: collaborator

Study Sites (4)

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

Location

Cancer Centre of Southeastern Ontario at Kingston

Kingston, Ontario, K7L 5P9, Canada

Location

Ottawa Hospital Research Institute

Ottawa, Ontario, K1H 8L6, Canada

Location

Related Publications (1)

• Goffin JR, Nicholas G, Mates M, Tu D, Chen E, Laurie SA, Juergens R, Robinson A, Goss G, Reaume M, Sun S, Christink K, Maize C, MacFarlan S, Sun X, Ritter H, Seymour L, Bradbury PA. Canadian Cancer Trials Group (CCTG) IND215: A phase Ib study of Selumetinib in patients with untreated advanced or metastatic NSCLC who are receiving standard chemotherapy regimens. Invest New Drugs. 2019 Jun;37(3):498-506. doi: 10.1007/s10637-018-0680-z. Epub 2018 Oct 13.

  PMID: 30317534 RESULT

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Paclitaxel; Carboplatin; AZD 6244; Pemetrexed; Cisplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Garth Nicholas

  Ottawa Health Research Institute - General Division

  STUDY CHAIR

• John Goffin

  Juravinski Cancer Centre at Hamilton Health Sciences

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: January 31, 2013
• First Posted: February 4, 2013
• Study Start: June 4, 2013
• Primary Completion: April 18, 2017
• Study Completion: April 2, 2019
• Last Updated: August 4, 2023

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (4)