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Non Small Cell Lung CancerPhase 1NCT01783197

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

A Phase 1 study testing Paclitaxel, Carboplatin and Selumetinib in people with Non Small Cell Lung Cancer, run by Canadian Cancer Trials Group at 4 sites in Canada.

Completed

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

Official record
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Trial 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… 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?
Paclitaxel, Carboplatin and Selumetinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
39 participants
Where
4 sitesCanada
Study dates
4 Jun 2013to 2 Apr 2019
Phase
Phase 1
Are there results?
None posted in the registry

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

  • 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
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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 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:
  • Previous major surgery is permitted provided it has been at least 14 days prior to patient registration 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:
  • Patients may not have received prior MEK inhibitors or any other tyrosine kinase inhibitor (including EGFR inhibitors of any kind).
  • Prior adjuvant 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, UNLESS patient is to be enrolled in the pemetrexed single agent cohort. Patients for this cohort must be candidates for single agent pemetrexed, have received no prior pemetrexed and have had no more than one prior chemotherapy regimen for advanced or metastatic disease.
  • Laboratory Requirements (must be done within 7 days prior to registration)
  • Hematology:
  • Neutrophils ≥ 1.5 x 10^9/L; Platelets ≥ 100 x 10^9/L
  • Biochemistry:
  • Creatinine Clearance ≥ 50 ml/min (calculated by Cockcroft and Gault equation) Total bilirubin ≤ 1.5 x ULN AST and ALT ≤ 2.5 x ULN (≤ 5x ULN in the presence of liver metastases)
  • 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 who cannot give informed consent (i.e. mentally incompetent patients, or those physically incapacitated such as comatose patients) are not to be recruited into the study. Patients competent but physically unable to sign the consent form may have the document signed by their nearest relative or legal guardian. Each patient will be provided with a full explanation of the study before consent is requested.
  • Patients must be accessible for treatment and follow-up. Patients registered on this trial must be treated and followed at the participating centre. This implies there must be reasonable geographical limits (for example: 1 ½ hour's driving distance) placed on patients being considered for this trial. Investigators must assure themselves the patients registered on this trial will be available for complete documentation of the treatment, adverse events, and follow-up.
  • Treatment is to begin within 2 working days of patient registration.

Who cannot join

  • 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)
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  • 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
  • Other patients with cardiac disease, who do not meet the exclusion criteria above, must have a baseline LVEF ≥ 55%.
  • 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.
  • Patients who require oral anticoagulants (coumadin) are eligible provided there is increased vigilance with respect to monitor INR, 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 or uncontrolled glaucoma (irrespective of IOP).
  • Pregnant or lactating women. Women of childbearing potential must have a urine pregnancy test proven negative within 7 days prior to registration. Men and women of child-bearing potential must agree to use adequate contraception.
  • Patients who do not agree to avoid excessive sun exposure and use adequate sunscreen protection.

Trial locations and contacts

4 sites in 1 country.

Canada4 sites

  • Juravinski Cancer Centre at Hamilton Health Sciences

    Hamilton, Ontario, L8V 5C2

  • Cancer Centre of Southeastern Ontario at Kingston

    Kingston, Ontario, K7L 5P9

  • Ottawa Hospital Research Institute

    Ottawa, Ontario, K1H 8L6

  • BCCA - Vancouver Cancer Centre

    Vancouver, British Columbia, V5Z 4E6

Other trials in Canada

About this study

Official title: A Phase Ib Study of Selumetinib in Patients With Previously Treated or Untreated Advanced/Metastatic NSCLC Who Are Receiving Standard Chemotherapy Regimens.

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.

Read the detailed description

The purpose of this study is to find the highest dose of a new drug, selumetinib, given in combination with standard chemotherapies, that can be tolerated without causing very severe side effects. This is done by starting at a dose lower than the one that does not cause side effects in animals. Participants are given selumetinib and are watched very closely to see what side effects they have and to make sure the side effects are not severe. If the side effects are not severe, then more potential participants are asked to join this study and are given a higher dose of selumetinib. Participants joining this study later on will take selumetinib at higher doses, take doses twice daily or take for more days in a 21 day period than participants who join earlier. This will continue until a dose is found that causes severe but temporary side effects. Doses higher than that will not be given.

Being tested
Paclitaxel, Carboplatin, Selumetinib, Pemetrexed, Cisplatin
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 NCT01783197
Study groupRoleWhat they receive
Paclitaxel and carboplain plus selumetinibExperimentalCohort 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.
Receives: Drug: Paclitaxel; Drug: Carboplatin; Drug: Selumetinib
pemetrexed and cisplain plus selumetinibExperimentalCohort 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.
Receives: Drug: Selumetinib; Drug: Pemetrexed; Drug: Cisplatin
pemetrexed plus selumetinibExperimentalCohort 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.
Receives: Drug: Selumetinib; Drug: Pemetrexed

What is being measured

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

  1. Maximum dose tolerability of Selumetinib in patients

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

    Measured: 24 months

Secondary outcomes (1)

  1. Pharmacokinetic response prediction to selumetinib

    pharmacokinetic (PK) profiles of selumetinib when given daily continuously in combination with chemotherapy; gene expression signatures/profiles and/or KRAS codon subtypes in tumour and/or tumour derived material that may influence response; the use of plasma as a potential source of circulating free tumour DNA (cfDNA) for the analysis of KRAS mutation status; and serum exploratory markers that may predict response to selumetinib; and preliminary assessment of efficacy in all patients and in expansion cohorts of up to 10 patients with KRAS positive NSCLC

    Measured: 24 months

Timeline

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

  1. First posted4 Feb 2013 (estimated)
  2. Study start4 Jun 2013
  3. Primary completion18 Apr 2017
  4. Study completion2 Apr 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 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
39 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01783197
Sponsor's protocol ID
I215
Status last verified
Apr 2020
First submitted
31 Jan 2013
Last updated
4 Aug 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 30317534

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Paclitaxel, Carboplatin and Selumetinib in people with Non Small Cell Lung Cancer, run by Canadian Cancer Trials Group at 4 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 30 inclusion and 20 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 4 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Maximum dose tolerability of Selumetinib in patients (time frame: 24 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 NCT01783197, 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 4 Aug 2023.

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