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

NCT02337530 | Completed Phase 2 Results DMC

• 1 other identifier: I219
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 12

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.

Conditions

Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (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.

  2 years and 5 months.

Secondary Outcomes (1)

• Progression Free Survival

  2 years 5 months

Study Arms (3)

Arm A

ACTIVE COMPARATOR

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

Arm B

ACTIVE COMPARATOR

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

Arm C

ACTIVE COMPARATOR

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

Interventions

Selumetinib DRUG

Arm A; Arm B

Pemetrexed DRUG

Arm A; Arm B; Arm C

Cisplatin DRUG

Arm A; Arm B; Arm C

Carboplatin DRUG

Arm A; Arm B; Arm C

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Canadian Cancer Trials Group: lead
• AstraZeneca: collaborator

Study Sites (12)

Tom Baker Cancer Centre

Calgary, Alberta, T2N 4N2, Canada

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

BCCA - Abbotsford Centre

Abbotsford, British Columbia, V2S 0C2, Canada

Location

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Regional Health Authority B, Zone 2

Saint John, New Brunswick, E2L 4L2, Canada

Location

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

Location

Cancer Centre of Southeastern Ontario at Kingston

Kingston, Ontario, K7L 5P9, Canada

Location

Lakeridge Health Oshawa

Oshawa, Ontario, L1G 2B9, Canada

Location

Ottawa Hospital Research Institute

Ottawa, Ontario, K1H 8L6, Canada

Location

Mount Sinai Hospital

Toronto, Ontario, M5G 1X5, Canada

Location

University Health Network

Toronto, Ontario, M5G 2M9, Canada

Location

CHUM - Hopital Notre-Dame

Montreal, Quebec, H2L 4M1, Canada

Location

Related Publications (1)

• 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.

  PMID: 31200828 RESULT

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

AZD 6244; Pemetrexed; Cisplatin; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals

Results Point of Contact

• Title: Lesely Seymour
• Organization: Canadian Cancer Trials Group

lseymour@ctg.queensu.ca

6135336430

Study Officials

• 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 CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 9, 2015
• First Posted: January 13, 2015
• Study Start: May 26, 2015
• Primary Completion: October 31, 2017
• Study Completion: June 18, 2019
• Last Updated: March 21, 2024
• Results First Posted: June 22, 2021

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (12)