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Selumetinib in Patients Receiving Pemetrexed and Platinum-based Chemotherapy in Advanced or Metastatic KRAS Wildtype or Unknown Non-Squamous Non-Small Cell Lung Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02337530
First Posted: January 13, 2015
Last Update Posted: October 25, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Canadian Cancer Trials Group
  Purpose
The purpose of this study is to find out what effects a new drug, selumetinib, has on lung cancer when receiving standard chemotherapy with pemetrexed and platinum-based chemotherapy.

Condition Intervention Phase
Non-Small Cell Lung Cancer Drug: Selumetinib Drug: Pemetrexed Drug: Cisplatin Drug: Carboplatin Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Phase II Trial of Selumetinib in Patients Receiving Standard Pemetrexed and Platinum-based Chemotherapy for the Treatment of Advanced or Metastatic KRAS Wildtype or Unknown Non-Squamous Non-Small Cell Lung Cancer

Resource links provided by NLM:


Further study details as provided by Canadian Cancer Trials Group:

Primary Outcome Measures:
  • Efficacy determined by objective response rate [ Time Frame: 3 years ]
    To determine the efficacy, as determined by objective response rate, of selumetinib (intermittent or continuous) in patients with NSCLC not known to have KRAS mutation receiving standard pemetrexed and platinum-based chemotherapy compared to chemotherapy alone.


Secondary Outcome Measures:
  • Severity of adverse events in patients [ Time Frame: 3 years ]
    To assess the tolerability of selumetinib in patients receiving pemetrexed and platinum-based chemotherapy.

  • Progression free survival [ Time Frame: 3 years ]
    To assess the progression free survival of patients receiving selumetinib with pemetrexed and platinum-based chemotherapy to those receiving pemetrexed and platinum-based chemotherapy alone


Enrollment: 62
Actual Study Start Date: February 5, 2015
Estimated Study Completion Date: February 2018
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm A

Selumetinib: 75mg/ bid PO given on days 2-19 Pemetrexed: 500mg/m^2 & Cisplatin or Carboplatin*: AUC6: 75mg/m^2 given on day 1 Schedule = q 21 days

*Must be specified at time of randomization. Patients who start on treatment with cisplatin may switch to carboplatin only after discussion with CCTG

Drug: Selumetinib Drug: Pemetrexed Drug: Cisplatin Drug: Carboplatin
Active Comparator: Arm B

Selumetinib: 75mg/ bid PO given on days 1-21 (continuous) Pemetrexed: 500mg/m^2 & Cisplatin*: 75mg/m^2 or carboplatin AUC 6 given on day 1 Schedule = q 21 days

**Must be specified at time of randomization. Patients who start on treatment with cisplatin may switch to carboplatin only after discussion with CCTG

Drug: Selumetinib Drug: Pemetrexed Drug: Cisplatin Drug: Carboplatin
Active Comparator: Arm C

Selumetinib: NOT GIVEN Pemetrexed: 500mg/m^2 & Cisplatin*: 75mg/m^2 or carboplatin AUC6 given on day 1 Schedule = q 21 days

*Must be specified at time of randomization. Patients who start on treatment with cisplatin may switch to carboplatin only after discussion with CCTG

Drug: Pemetrexed Drug: Cisplatin Drug: Carboplatin

Detailed Description:
This research is being done to see whether selumetinib improves the results of standard chemotherapy. The standard or usual treatment for this disease is treatment with chemotherapy alone.
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have histologically and/or cytologically confirmed non-squamous, KRAS wildtype or unknown, non-small cell lung cancer that is stage IIIB or IV, metastatic or unresectable and for which standard curative measures do not exist.
  • All patients must have a formalin fixed paraffin embedded tumour block (from primary or metastatic tumour) available for correlative studies and must have provided informed consent for the release of the block for correlative studies.
  • Patients must have at least one site of disease which is unidimensionally measurable as follows:
  • Measurable disease defined as at least one target lesion that has not been irradiated or has progressed after radiation 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 randomization (within 35 days if negative).
  • Age ≥ 18 years.
  • ECOG performance status 0 or 1
  • Previous Therapy Surgery: Previous major surgery is permitted provided it has been at least 14 days prior to patient randomization and that wound healing has occurred.

Radiation: Prior external beam radiation is permitted provided a minimum of 4 weeks has elapsed between the last dose and enrollment to the trial.

Chemotherapy and systemic therapy: Prior therapy with ALK inhibitors is permissible. Patients may not have received prior MEK inhibitors or any other tyrosine kinase inhibitor (including EGFR inhibitors of any kind). Patients may have received vaccines, immunotherapy or other agents that are not MEK/tyrosine kinase inhibitors in the adjuvant setting or for advanced or metastatic disease.

Prior adjuvant platinum-based chemotherapy or combined chemoradiotherapy with curative intent is permissible provided completed at least one year prior to enrollment. No prior cytotoxic chemotherapy for advanced / metastatic disease is permissible.

- Laboratory Requirements (must be done within 7 days prior to randomization)

Neutrophils ≥ 1.5 x 10^9/L Platelets ≥ 100 x 10^9/L

Biochemistry:

Creatinine Clearance* ≥ 50 ml/min Total bilirubin ≤ 1.5 x ULN AST and ALT ≤ 2.5 x ULN (if liver metastases ≤ 5x UNL permissible providing ALP also ≤ 6 x UNL)

* Creatinine clearance to be measured directly by 24 hour urine sampling or as calculated by appropriate formula below: Females: GFR = 1.04 x (140-age) x weight in kg/serum creatinine in μmol/L Males: GFR = 1.23 x (140-age) x weight in kg/serum creatinine in μmol/L

  • Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment in the trial to document their willingness to participate
  • Patients must be accessible for treatment and follow-up. Patients randomized on this trial must be treated and followed at the participating centre
  • In accordance with CCTG policy, protocol treatment is to begin within 2 working days of patient randomization

Exclusion Criteria:

  • Patients with a history of other untreated malignancies or malignancies which required therapy within the past 2 years
  • No symptomatic brain metastases or spinal cord compression. Patients with asymptomatic brain/spinal cord metastasis who are not planned for radiation, or who have been treated and are stable off steroids (or on a decreasing dose) and anticonvulsants are eligible.
  • 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 > 100 bpm at rest
  • severe valvular heart disease Patients with cardiac disease, who do not meet the exclusion criteria above, must have a baseline LVEF ≥ 50%.
  • Any evidence of severe or uncontrolled systemic disease, active infection, active bleeding diatheses or renal transplant, including any patient known to have hepatitis B, hepatitis C or human immunodeficiency virus (HIV).
  • Patients who have neuropathy > grade 1 or other conditions precluding treatment with the standard chemotherapy regimen planned. Consult CCTG for patients with localised neuropathies as such patients may be eligible.
  • 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 randomization or 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) and not take vitamin E supplements or multivitamin supplements.

Patients who require oral anticoagulants (Coumadin) are eligible provided there is increased vigilance with respect to INR monitoring upon initiation of dosing with selumetinib. If medically appropriate and treatment available, the investigator should consider switching these patients to LMW heparin.

  • Patients with current or past history of central serous retinopathy or retinal vein occlusion, high intraocular pressure (≥ 21mm) or uncontrolled glaucoma (irrespective of IOP). Patients with visual symptoms should undergo ophthalmologic examination prior to randomization.
  • Pregnant or lactating women. Women of childbearing potential must have a urine pregnancy test proven negative within 7 days prior to randomization. Men and women of childbearing potential must agree to use adequate contraception
  • Patients who do not agree to avoid excessive sun exposure and use adequate sunscreen protection.
  • Selumetinib-specific precautions for patients of Asian ethnicity:

Plasma exposure of selumetinib (Cmax and AUC) is higher, at a population level, in subjects of Asian descent by approximately 1.5- to 2-fold in non-Japanese Asians and Japanese subjects, compared with Western subjects. However, there is overlap in the range of exposure experienced by Asian and Western subjects and the higher average plasma exposure was not associated with a change in the tolerability profile of single dose selumetinib.

Investigators should make a clinical judgment as to whether the potential risk of experiencing higher selumetinib plasma exposure and potential adverse events outweighs the potential benefit of treatment with selumetinib.

  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02337530


Locations
Canada, Alberta
Tom Baker Cancer Centre
Calgary, Alberta, Canada, T2N 4N2
Cross Cancer Institute
Edmonton, Alberta, Canada, T6G 1Z2
Canada, British Columbia
BCCA - Abbotsford Centre
Abbotsford, British Columbia, Canada, V2S 0C2
BCCA - Vancouver Cancer Centre
Vancouver, British Columbia, Canada, V5Z 4E6
Canada, New Brunswick
Regional Health Authority B, Zone 2
Saint John, New Brunswick, Canada, E2L 4L2
Canada, Ontario
Juravinski Cancer Centre at Hamilton Health Sciences
Hamilton, Ontario, Canada, L8V 5C2
Cancer Centre of Southeastern Ontario at Kingston
Kingston, Ontario, Canada, K7L 5P9
Lakeridge Health Oshawa
Oshawa, Ontario, Canada, L1G 2B9
Ottawa Hospital Research Institute
Ottawa, Ontario, Canada, K1H 8L6
Mount Sinai Hospital
Toronto, Ontario, Canada, M5G 1X5
University Health Network
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
CHUM - Hopital Notre-Dame
Montreal, Quebec, Canada, H2L 4M1
Sponsors and Collaborators
Canadian Cancer Trials Group
AstraZeneca
Investigators
Study Chair: Penelope A Bradbury Univ. Health Network-Princess Margaret Hospital, Toronto ON Canada
Study Chair: Barbara Lynn Melosky BCCA - Vancouver Cancer Centre, Vancouver BC Canada
  More Information

Responsible Party: Canadian Cancer Trials Group
ClinicalTrials.gov Identifier: NCT02337530     History of Changes
Other Study ID Numbers: I219
First Submitted: January 9, 2015
First Posted: January 13, 2015
Last Update Posted: October 25, 2017
Last Verified: March 2017

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Cisplatin
Carboplatin
Pemetrexed
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors