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Non-Small Cell Lung CancerPhase 2NCT02337530

Selumetinib in Patients Receiving Pemetrexed and Platinum-based Chemotherapy in Advanced or Metastatic KRAS Wildtype or Unknown Non-Squamous NSCLC

A Phase 2 study testing Selumetinib, Pemetrexed and Cisplatin in people with Non-Small Cell Lung Cancer, run by Canadian Cancer Trials Group at 12 sites in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non-Small Cell Lung Cancer
What is being tested?
Selumetinib, Pemetrexed and Cisplatin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
62 participants
Where
12 sitesCanada
Study dates
26 May 2015to 18 Jun 2019
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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.

Trial locations and contacts

12 sites in 1 country.

12 sites in 1 country

Canada12 sites

  • BCCA - Abbotsford Centre

    Abbotsford British Columbia, British Columbia, V2S 0C2

  • Tom Baker Cancer Centre

    Calgary, Alberta, T2N 4N2

  • Cross Cancer Institute

    Edmonton, Alberta, T6G 1Z2

  • Juravinski Cancer Centre at Hamilton Health Sciences

    Hamilton, Ontario, L8V 5C2

  • Cancer Centre of Southeastern Ontario at Kingston

    Kingston, Ontario, K7L 5P9

  • CHUM - Hopital Notre-Dame

    Montreal, Quebec, H2L 4M1

  • Lakeridge Health Oshawa

    Oshawa, Ontario, L1G 2B9

  • Ottawa Hospital Research Institute

    Ottawa, Ontario, K1H 8L6

  • Regional Health Authority B, Zone 2

    Saint John, New Brunswick, E2L 4L2

  • Mount Sinai Hospital

    Toronto, Ontario, M5G 1X5

  • University Health Network

    Toronto, Ontario, M5G 2M9

  • BCCA - Vancouver Cancer Centre

    Vancouver, British Columbia, V5Z 4E6

Other trials in Canada

About this study

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

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.

Read the 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.

Being tested
Selumetinib, Pemetrexed, Cisplatin, Carboplatin
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT02337530
Study groupRoleWhat they receive
Arm AActive comparatorSelumetinib: 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
Receives: Drug: Selumetinib; Drug: Pemetrexed; Drug: Cisplatin; Drug: Carboplatin
Arm BActive comparatorSelumetinib: 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
Receives: Drug: Selumetinib; Drug: Pemetrexed; Drug: Cisplatin; Drug: Carboplatin
Arm CActive comparatorSelumetinib: 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
Receives: Drug: Pemetrexed; Drug: Cisplatin; Drug: Carboplatin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective Response Rate

    Defined as percentage of participants with objective response over all participants randomized. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Objective Response (OR) = CR + PR.

    Measured: 2 years and 5 months.

Secondary outcomes (1)

  1. Progression Free Survival

    Defined as the time from randomization to the first objective documentation of disease progression, defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions, or death due to any cause with patients who had not progressed or died at the time of final analysis censored on the date of the last tumour assessment.

    Measured: 2 years 5 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Jan 2015 (estimated)
  2. Study start26 May 2015
  3. Primary completion31 Oct 2017
  4. Study completion18 Jun 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
62 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02337530
Sponsor's protocol ID
I219
Status last verified
Mar 2024
First submitted
9 Jan 2015
Last updated
21 Mar 2024
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Melosky B, Bradbury P, Tu D, Florescu M, Reiman A, Nicholas G, Basappa N, Rothenstein J, Goffin JR, Laurie SA, Wheatley-Price P, Leighl N, Goss G, Reaume MN, Butts C, Murray N, Card C, Ko J, Blais N, Gray S, Lui H, Brown-Walker P, Kaurah P, Prentice LM, Seymour L. Selumetinib in patients receiving standard pemetrexed and platinum-based chemotherapy for advanced or metastatic KRAS wildtype or unknown non-squamous non-small cell lung cancer: A randomized, multicenter, phase II study. Canadian Cancer Trials Group (CCTG) IND.219. Lung Cancer. 2019 Jul;133:48-55. doi: 10.1016/j.lungcan.2019.04.027. Epub 2019 May 1.

    PubMed 31200828

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Selumetinib, Pemetrexed and Cisplatin in people with Non-Small Cell Lung Cancer, run by Canadian Cancer Trials Group at 12 sites in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (time frame: 2 years and 5 months.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02337530, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Mar 2024.

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