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

Sponsor
Canadian Cancer Trials Group (Other)
Overall Status
Completed
CT.gov ID
NCT02337530
Collaborator
AstraZeneca (Industry)
62
12
3
52.4
5.2
0.1

Study Details

Study Description

Brief 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.

Condition or Disease Intervention/Treatment Phase
Phase 2

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
62 participants
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
Actual Study Start Date :
Feb 5, 2015
Actual Primary Completion Date :
Oct 31, 2017
Actual Study Completion Date :
Jun 18, 2019

Arms and Interventions

Arm Intervention/Treatment
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

Outcome Measures

Primary Outcome Measures

  1. Objective Response Rate [From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years.]

    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.

Secondary Outcome Measures

  1. Progression Free Survival [3 years]

    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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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 109/L Platelets ≥ 100 x 109/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

Locations

Site City State Country Postal Code
1 Tom Baker Cancer Centre Calgary Alberta Canada T2N 4N2
2 Cross Cancer Institute Edmonton Alberta Canada T6G 1Z2
3 BCCA - Abbotsford Centre Abbotsford British Columbia Canada V2S 0C2
4 BCCA - Vancouver Cancer Centre Vancouver British Columbia Canada V5Z 4E6
5 Regional Health Authority B, Zone 2 Saint John New Brunswick Canada E2L 4L2
6 Juravinski Cancer Centre at Hamilton Health Sciences Hamilton Ontario Canada L8V 5C2
7 Cancer Centre of Southeastern Ontario at Kingston Kingston Ontario Canada K7L 5P9
8 Lakeridge Health Oshawa Oshawa Ontario Canada L1G 2B9
9 Ottawa Hospital Research Institute Ottawa Ontario Canada K1H 8L6
10 Mount Sinai Hospital Toronto Ontario Canada M5G 1X5
11 University Health Network Toronto Ontario Canada M5G 2M9
12 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

Study Documents (Full-Text)

More Information

Publications

None provided.
Responsible Party:
Canadian Cancer Trials Group
ClinicalTrials.gov Identifier:
NCT02337530
Other Study ID Numbers:
  • I219
First Posted:
Jan 13, 2015
Last Update Posted:
Jun 22, 2021
Last Verified:
May 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details Subjects were recruited between February 2015 and May 2017 from cancer centres in Canada.
Pre-assignment Detail
Arm/Group Title Intermittent Oral Selumatinib With Pemetrexed and Platinum Continuous Oral Selumatinib With Pemetrexed and Platinum Pemetrexed and Platinum Alone
Arm/Group Description 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 Selumetinib Pemetrexed Cisplatin Carboplatin 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 Selumetinib Pemetrexed Cisplatin Carboplatin 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 Pemetrexed Cisplatin Carboplatin
Period Title: Overall Study
STARTED 20 21 21
COMPLETED 20 21 21
NOT COMPLETED 0 0 0

Baseline Characteristics

Arm/Group Title Intermittent Oral Selumatinib With Pemetrexed and Platinum Continuous Oral Selumatinib With Pemetrexed and Platinum Pemetrexed and Platinum Alone Total
Arm/Group Description 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 Selumetinib Pemetrexed Cisplatin Carboplatin 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 Selumetinib Pemetrexed Cisplatin Carboplatin 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 Pemetrexed Cisplatin Carboplatin Total of all reporting groups
Overall Participants 20 21 21 62
Age (Count of Participants)
<=18 years
0
0%
0
0%
0
0%
0
0%
Between 18 and 65 years
11
55%
12
57.1%
10
47.6%
33
53.2%
>=65 years
9
45%
9
42.9%
11
52.4%
29
46.8%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]
68
66
65
66
Sex: Female, Male (Count of Participants)
Female
10
50%
11
52.4%
11
52.4%
32
51.6%
Male
10
50%
10
47.6%
10
47.6%
30
48.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino
0
0%
0
0%
0
0%
0
0%
Not Hispanic or Latino
20
100%
21
100%
21
100%
62
100%
Unknown or Not Reported
0
0%
0
0%
0
0%
0
0%
Region of Enrollment (participants) [Number]
Canada
20
100%
21
100%
21
100%
62
100%
Eastern Cooperative Oncology Group (ECOG) performance status (Count of Participants)
0
4
20%
3
14.3%
3
14.3%
10
16.1%
1
16
80%
18
85.7%
18
85.7%
52
83.9%

Outcome Measures

1. Primary Outcome
Title Objective Response Rate
Description 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.
Time Frame From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years.

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Intermittent Oral Selumatinib With Pemetrexed and Platinum Continuous Oral Selumatinib With Pemetrexed and Platinum Pemetrexed and Platinum Alone
Arm/Group Description 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 Selumetinib Pemetrexed Cisplatin Carboplatin 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 Selumetinib Pemetrexed Cisplatin Carboplatin 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 Pemetrexed Cisplatin Carboplatin
Measure Participants 20 21 21
Responded
6
30%
14
66.7%
5
23.8%
Not Responded
14
70%
7
33.3%
16
76.2%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Intermittent Oral Selumatinib With Pemetrexed and Platinum, Pemetrexed and Platinum Alone
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.73
Comments
Method Fisher Exact
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.37
Confidence Interval (2-Sided) 95%
0.28 to 7.01
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Continuous Oral Selumatinib With Pemetrexed and Platinum, Pemetrexed and Platinum Alone
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments
Method Fisher Exact
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 6.40
Confidence Interval (2-Sided) 95%
1.65 to 24.8
Parameter Dispersion Type:
Value:
Estimation Comments
2. Secondary Outcome
Title Progression Free Survival
Description 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.
Time Frame 3 years

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Intermittent Oral Selumatinib With Pemetrexed and Platinum Continuous Oral Selumatinib With Pemetrexed and Platinum Pemetrexed and Platinum Alone
Arm/Group Description 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 Selumetinib Pemetrexed Cisplatin Carboplatin 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 Selumetinib Pemetrexed Cisplatin Carboplatin 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 Pemetrexed Cisplatin Carboplatin
Measure Participants 20 21 21
Median (95% Confidence Interval) [months]
7.2
6.9
4.0
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Intermittent Oral Selumatinib With Pemetrexed and Platinum, Continuous Oral Selumatinib With Pemetrexed and Platinum
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.56
Comments
Method Log Rank
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.82
Confidence Interval (2-Sided) 95%
0.42 to 1.60
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Continuous Oral Selumatinib With Pemetrexed and Platinum, Pemetrexed and Platinum Alone
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.44
Comments
Method Log Rank
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.77
Confidence Interval (2-Sided) 95%
0.40 to 1.49
Parameter Dispersion Type:
Value:
Estimation Comments

Adverse Events

Time Frame 3 years
Adverse Event Reporting Description
Arm/Group Title Intermittent Oral Selumatinib With Pemetrexed and Platinum Continuous Oral Selumatinib With Pemetrexed and Platinum Pemetrexed and Platinum Alone
Arm/Group Description 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 Selumetinib Pemetrexed Cisplatin Carboplatin 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 Selumetinib Pemetrexed Cisplatin Carboplatin 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 Pemetrexed Cisplatin Carboplatin
All Cause Mortality
Intermittent Oral Selumatinib With Pemetrexed and Platinum Continuous Oral Selumatinib With Pemetrexed and Platinum Pemetrexed and Platinum Alone
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 13/20 (65%) 15/21 (71.4%) 9/21 (42.9%)
Serious Adverse Events
Intermittent Oral Selumatinib With Pemetrexed and Platinum Continuous Oral Selumatinib With Pemetrexed and Platinum Pemetrexed and Platinum Alone
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 14/20 (70%) 14/21 (66.7%) 9/21 (42.9%)
Blood and lymphatic system disorders
Febrile neutropenia 0/20 (0%) 1/21 (4.8%) 0/21 (0%)
Leukocytosis 0/20 (0%) 0/21 (0%) 1/21 (4.8%)
Cardiac disorders
Acute coronary syndrome 1/20 (5%) 0/21 (0%) 0/21 (0%)
Atrial fibrillation 1/20 (5%) 1/21 (4.8%) 0/21 (0%)
Chest pain - cardiac 0/20 (0%) 0/21 (0%) 1/21 (4.8%)
Eye disorders
Other eye disorders 1/20 (5%) 0/21 (0%) 0/21 (0%)
Gastrointestinal disorders
Colonic perforation 0/20 (0%) 1/21 (4.8%) 0/21 (0%)
Constipation 0/20 (0%) 2/21 (9.5%) 0/21 (0%)
Diarrhea 1/20 (5%) 0/21 (0%) 1/21 (4.8%)
Duodenal hemorrhage 1/20 (5%) 0/21 (0%) 0/21 (0%)
Enterocolitis 1/20 (5%) 0/21 (0%) 0/21 (0%)
Nausea 1/20 (5%) 3/21 (14.3%) 0/21 (0%)
Vomiting 1/20 (5%) 3/21 (14.3%) 0/21 (0%)
General disorders
Edema limbs 0/20 (0%) 1/21 (4.8%) 0/21 (0%)
Fatigue 1/20 (5%) 1/21 (4.8%) 2/21 (9.5%)
Infections and infestations
Bronchial infection 0/20 (0%) 0/21 (0%) 1/21 (4.8%)
Enterocolitis infectious 1/20 (5%) 0/21 (0%) 0/21 (0%)
Lung infection 2/20 (10%) 2/21 (9.5%) 2/21 (9.5%)
Pleural infection 1/20 (5%) 0/21 (0%) 0/21 (0%)
Sepsis 2/20 (10%) 1/21 (4.8%) 1/21 (4.8%)
Injury, poisoning and procedural complications
Fall 1/20 (5%) 0/21 (0%) 0/21 (0%)
Hip fracture 0/20 (0%) 1/21 (4.8%) 0/21 (0%)
Metabolism and nutrition disorders
Dehydration 1/20 (5%) 4/21 (19%) 0/21 (0%)
Hypokalemia 1/20 (5%) 0/21 (0%) 0/21 (0%)
Hyponatremia 0/20 (0%) 1/21 (4.8%) 0/21 (0%)
Musculoskeletal and connective tissue disorders
Generalized muscle weakness 0/20 (0%) 1/21 (4.8%) 0/21 (0%)
Muscle weakness left-sided 0/20 (0%) 0/21 (0%) 1/21 (4.8%)
Neck pain 1/20 (5%) 0/21 (0%) 0/21 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Other neoplasms benign, malignant and unspecified 2/20 (10%) 1/21 (4.8%) 0/21 (0%)
Nervous system disorders
Depressed level of consciousness 1/20 (5%) 0/21 (0%) 0/21 (0%)
Leukoencephalopathy 1/20 (5%) 0/21 (0%) 0/21 (0%)
Seizure 0/20 (0%) 1/21 (4.8%) 0/21 (0%)
Stroke 1/20 (5%) 0/21 (0%) 1/21 (4.8%)
Syncope 0/20 (0%) 0/21 (0%) 1/21 (4.8%)
Psychiatric disorders
Delusions 0/20 (0%) 0/21 (0%) 1/21 (4.8%)
Hallucinations 0/20 (0%) 0/21 (0%) 1/21 (4.8%)
Renal and urinary disorders
Acute kidney injury 1/20 (5%) 0/21 (0%) 1/21 (4.8%)
Respiratory, thoracic and mediastinal disorders
Hypoxia 0/20 (0%) 0/21 (0%) 1/21 (4.8%)
Pneumonitis 0/20 (0%) 1/21 (4.8%) 0/21 (0%)
Respiratory failure 1/20 (5%) 0/21 (0%) 1/21 (4.8%)
Vascular disorders
Hypotension 0/20 (0%) 2/21 (9.5%) 0/21 (0%)
Thromboembolic event 6/20 (30%) 1/21 (4.8%) 1/21 (4.8%)
Vasculitis 0/20 (0%) 1/21 (4.8%) 0/21 (0%)
Other (Not Including Serious) Adverse Events
Intermittent Oral Selumatinib With Pemetrexed and Platinum Continuous Oral Selumatinib With Pemetrexed and Platinum Pemetrexed and Platinum Alone
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 20/20 (100%) 21/21 (100%) 21/21 (100%)
Cardiac disorders
Acute coronary syndrome 1/20 (5%) 0/21 (0%) 0/21 (0%)
Atrial fibrillation 2/20 (10%) 2/21 (9.5%) 0/21 (0%)
Ear and labyrinth disorders
Ear pain 0/20 (0%) 2/21 (9.5%) 0/21 (0%)
Hearing impaired 1/20 (5%) 0/21 (0%) 4/21 (19%)
Tinnitus 2/20 (10%) 4/21 (19%) 3/21 (14.3%)
Vertigo 0/20 (0%) 3/21 (14.3%) 0/21 (0%)
Eye disorders
Blurred vision 3/20 (15%) 2/21 (9.5%) 0/21 (0%)
Cataract 1/20 (5%) 0/21 (0%) 0/21 (0%)
Dry eye 2/20 (10%) 1/21 (4.8%) 1/21 (4.8%)
Watering eyes 4/20 (20%) 3/21 (14.3%) 6/21 (28.6%)
Other eye disorders 2/20 (10%) 1/21 (4.8%) 1/21 (4.8%)
Gastrointestinal disorders
Abdominal pain 4/20 (20%) 7/21 (33.3%) 3/21 (14.3%)
Bloating 4/20 (20%) 0/21 (0%) 0/21 (0%)
Colonic hemorrhage 1/20 (5%) 0/21 (0%) 0/21 (0%)
Constipation 12/20 (60%) 15/21 (71.4%) 18/21 (85.7%)
Diarrhea 11/20 (55%) 13/21 (61.9%) 9/21 (42.9%)
Dry mouth 4/20 (20%) 2/21 (9.5%) 0/21 (0%)
Duodenal ulcer 1/20 (5%) 0/21 (0%) 0/21 (0%)
Dyspepsia 5/20 (25%) 5/21 (23.8%) 3/21 (14.3%)
Esophagitis 1/20 (5%) 0/21 (0%) 0/21 (0%)
Gastroesophageal reflux disease 2/20 (10%) 4/21 (19%) 2/21 (9.5%)
Hemorrhoidal hemorrhage 1/20 (5%) 0/21 (0%) 0/21 (0%)
Hemorrhoids 3/20 (15%) 1/21 (4.8%) 2/21 (9.5%)
Lip pain 1/20 (5%) 0/21 (0%) 0/21 (0%)
Mucositis oral 3/20 (15%) 9/21 (42.9%) 6/21 (28.6%)
Nausea 14/20 (70%) 16/21 (76.2%) 17/21 (81%)
Oral hemorrhage 0/20 (0%) 2/21 (9.5%) 0/21 (0%)
Oral pain 2/20 (10%) 1/21 (4.8%) 1/21 (4.8%)
Rectal pain 1/20 (5%) 0/21 (0%) 0/21 (0%)
Stomach pain 1/20 (5%) 2/21 (9.5%) 0/21 (0%)
Vomiting 12/20 (60%) 16/21 (76.2%) 13/21 (61.9%)
Other gastrointestinal disorders 1/20 (5%) 2/21 (9.5%) 0/21 (0%)
General disorders
Chills 0/20 (0%) 2/21 (9.5%) 1/21 (4.8%)
Edema face 4/20 (20%) 5/21 (23.8%) 4/21 (19%)
Edema limbs 11/20 (55%) 16/21 (76.2%) 11/21 (52.4%)
Fatigue 19/20 (95%) 20/21 (95.2%) 18/21 (85.7%)
Fever 3/20 (15%) 2/21 (9.5%) 2/21 (9.5%)
Flu like symptoms 1/20 (5%) 2/21 (9.5%) 1/21 (4.8%)
Localized edema 0/20 (0%) 2/21 (9.5%) 0/21 (0%)
Non-cardiac chest pain 4/20 (20%) 3/21 (14.3%) 5/21 (23.8%)
Pain 4/20 (20%) 5/21 (23.8%) 4/21 (19%)
Other general disorders, administration site conditions 1/20 (5%) 0/21 (0%) 0/21 (0%)
Immune system disorders
Allergic reaction 1/20 (5%) 0/21 (0%) 1/21 (4.8%)
Infections and infestations
Enterocolitis infectious 1/20 (5%) 0/21 (0%) 0/21 (0%)
Lung infection 2/20 (10%) 0/21 (0%) 2/21 (9.5%)
Mucosal infection 3/20 (15%) 4/21 (19%) 0/21 (0%)
Paronychia 1/20 (5%) 1/21 (4.8%) 0/21 (0%)
Rash pustular 1/20 (5%) 0/21 (0%) 0/21 (0%)
Sinusitis 1/20 (5%) 0/21 (0%) 0/21 (0%)
Skin infection 3/20 (15%) 4/21 (19%) 0/21 (0%)
Upper respiratory infection 2/20 (10%) 2/21 (9.5%) 3/21 (14.3%)
Urinary tract infection 2/20 (10%) 1/21 (4.8%) 1/21 (4.8%)
Other infections and infestations 2/20 (10%) 2/21 (9.5%) 2/21 (9.5%)
Injury, poisoning and procedural complications
Bruising 0/20 (0%) 2/21 (9.5%) 0/21 (0%)
Fall 2/20 (10%) 0/21 (0%) 0/21 (0%)
Fracture 1/20 (5%) 0/21 (0%) 0/21 (0%)
Investigations
Weight loss 1/20 (5%) 1/21 (4.8%) 0/21 (0%)
Metabolism and nutrition disorders
Anorexia 11/20 (55%) 15/21 (71.4%) 11/21 (52.4%)
Dehydration 4/20 (20%) 5/21 (23.8%) 1/21 (4.8%)
Hypoglycemia 0/20 (0%) 2/21 (9.5%) 0/21 (0%)
Hypokalemia 1/20 (5%) 3/21 (14.3%) 1/21 (4.8%)
Hypomagnesemia 4/20 (20%) 4/21 (19%) 2/21 (9.5%)
Hyponatremia 1/20 (5%) 1/21 (4.8%) 0/21 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia 4/20 (20%) 3/21 (14.3%) 0/21 (0%)
Back pain 8/20 (40%) 4/21 (19%) 11/21 (52.4%)
Bone pain 1/20 (5%) 1/21 (4.8%) 4/21 (19%)
Chest wall pain 1/20 (5%) 3/21 (14.3%) 4/21 (19%)
Flank pain 0/20 (0%) 1/21 (4.8%) 2/21 (9.5%)
Generalized muscle weakness 3/20 (15%) 3/21 (14.3%) 1/21 (4.8%)
Muscle weakness left-sided 0/20 (0%) 0/21 (0%) 2/21 (9.5%)
Muscle weakness lower limb 0/20 (0%) 2/21 (9.5%) 1/21 (4.8%)
Myalgia 2/20 (10%) 0/21 (0%) 2/21 (9.5%)
Neck pain 1/20 (5%) 3/21 (14.3%) 1/21 (4.8%)
Pain in extremity 5/20 (25%) 7/21 (33.3%) 5/21 (23.8%)
Nervous system disorders
Dizziness 1/20 (5%) 10/21 (47.6%) 5/21 (23.8%)
Dysgeusia 2/20 (10%) 4/21 (19%) 2/21 (9.5%)
Headache 6/20 (30%) 9/21 (42.9%) 7/21 (33.3%)
Memory impairment 1/20 (5%) 1/21 (4.8%) 0/21 (0%)
Paresthesia 0/20 (0%) 0/21 (0%) 2/21 (9.5%)
Peripheral motor neuropathy 0/20 (0%) 3/21 (14.3%) 1/21 (4.8%)
Peripheral sensory neuropathy 6/20 (30%) 4/21 (19%) 5/21 (23.8%)
Syncope 1/20 (5%) 2/21 (9.5%) 0/21 (0%)
Tremor 1/20 (5%) 1/21 (4.8%) 0/21 (0%)
Other nervous system disorders 0/20 (0%) 1/21 (4.8%) 2/21 (9.5%)
Psychiatric disorders
Anxiety 3/20 (15%) 3/21 (14.3%) 6/21 (28.6%)
Confusion 1/20 (5%) 0/21 (0%) 0/21 (0%)
Depression 3/20 (15%) 0/21 (0%) 1/21 (4.8%)
Insomnia 9/20 (45%) 9/21 (42.9%) 6/21 (28.6%)
Renal and urinary disorders
Acute kidney injury 1/20 (5%) 0/21 (0%) 0/21 (0%)
Urinary frequency 1/20 (5%) 0/21 (0%) 0/21 (0%)
Urinary incontinence 1/20 (5%) 0/21 (0%) 0/21 (0%)
Reproductive system and breast disorders
Breast pain 1/20 (5%) 0/21 (0%) 1/21 (4.8%)
Pelvic pain 0/20 (0%) 3/21 (14.3%) 1/21 (4.8%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis 3/20 (15%) 2/21 (9.5%) 1/21 (4.8%)
Bronchial obstruction 1/20 (5%) 0/21 (0%) 0/21 (0%)
Cough 14/20 (70%) 15/21 (71.4%) 16/21 (76.2%)
Dyspnea 10/20 (50%) 16/21 (76.2%) 14/21 (66.7%)
Epistaxis 2/20 (10%) 3/21 (14.3%) 1/21 (4.8%)
Hiccups 1/20 (5%) 1/21 (4.8%) 1/21 (4.8%)
Hoarseness 4/20 (20%) 1/21 (4.8%) 3/21 (14.3%)
Laryngeal inflammation 1/20 (5%) 0/21 (0%) 0/21 (0%)
Nasal congestion 2/20 (10%) 2/21 (9.5%) 1/21 (4.8%)
Pharyngeal mucositis 1/20 (5%) 0/21 (0%) 0/21 (0%)
Pleuritic pain 1/20 (5%) 0/21 (0%) 1/21 (4.8%)
Postnasal drip 1/20 (5%) 1/21 (4.8%) 0/21 (0%)
Productive cough 3/20 (15%) 1/21 (4.8%) 1/21 (4.8%)
Pulmonary hypertension 1/20 (5%) 0/21 (0%) 0/21 (0%)
Sore throat 2/20 (10%) 5/21 (23.8%) 1/21 (4.8%)
Other respiratory, thoracic and mediastinal disorders 2/20 (10%) 0/21 (0%) 0/21 (0%)
Skin and subcutaneous tissue disorders
Alopecia 2/20 (10%) 4/21 (19%) 1/21 (4.8%)
Dry skin 5/20 (25%) 6/21 (28.6%) 2/21 (9.5%)
Hyperhidrosis 1/20 (5%) 0/21 (0%) 0/21 (0%)
Pain of skin 1/20 (5%) 1/21 (4.8%) 0/21 (0%)
Periorbital edema 4/20 (20%) 7/21 (33.3%) 2/21 (9.5%)
Pruritus 4/20 (20%) 3/21 (14.3%) 0/21 (0%)
Rash acneiform 11/20 (55%) 9/21 (42.9%) 2/21 (9.5%)
Rash maculo-papular 4/20 (20%) 7/21 (33.3%) 1/21 (4.8%)
Scalp pain 1/20 (5%) 1/21 (4.8%) 0/21 (0%)
Skin induration 1/20 (5%) 0/21 (0%) 0/21 (0%)
Other skin and subcutaneous tissue disorders 2/20 (10%) 3/21 (14.3%) 3/21 (14.3%)
Vascular disorders
Hematoma 1/20 (5%) 0/21 (0%) 0/21 (0%)
Hot flashes 3/20 (15%) 0/21 (0%) 0/21 (0%)
Hypertension 2/20 (10%) 3/21 (14.3%) 2/21 (9.5%)
Hypotension 1/20 (5%) 5/21 (23.8%) 0/21 (0%)
Thromboembolic event 4/20 (20%) 8/21 (38.1%) 5/21 (23.8%)
Visceral arterial ischemia 1/20 (5%) 0/21 (0%) 0/21 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Name/Title Lesely Seymour
Organization Canadian Cancer Trials Group
Phone 6135336430
Email lseymour@ctg.queensu.ca
Responsible Party:
Canadian Cancer Trials Group
ClinicalTrials.gov Identifier:
NCT02337530
Other Study ID Numbers:
  • I219
First Posted:
Jan 13, 2015
Last Update Posted:
Jun 22, 2021
Last Verified:
May 1, 2021