Selumetinib in Patients Receiving Pemetrexed and Platinum-based Chemotherapy in Advanced or Metastatic KRAS Wildtype or Unknown Non-Squamous NSCLC
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
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
- 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
- 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
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.- I219
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
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 |
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
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 |
lseymour@ctg.queensu.ca |
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