Selumetinib and Paclitaxel as Second-Line Treatment in Treating Patients With Stage IIIB-IV Non-small Cell Lung Cancer
A Randomized, Open-Label, Phase I Trial of Continuous, Intermittent, and Pulsatile Selumetinib (AZD6244) Plus Paclitaxel as Second-Line Treatment for Stage IIIB or IV Non-small Cell Lung Cancer (NSCLC)
4 other identifiers
interventional
23
1 country
1
Brief Summary
This randomized phase I trial is studying the side effects and the best dose of selumetinib when given together with paclitaxel as a second line therapy in treating patients with stage IIIB-IV non-small cell lung cancer (NSCLC). Selumetinib may stop or slow the growth of tumor cells by blocking a protein called mitogen-activated protein kinase (MEK) that is needed for cell growth. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving selumetinib together with paclitaxel may kill more tumor cells.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Jul 2016
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 14, 2015
CompletedFirst Posted
Study publicly available on registry
July 21, 2015
CompletedStudy Start
First participant enrolled
July 21, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 16, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
July 16, 2020
CompletedMarch 21, 2023
March 1, 2023
4 years
July 14, 2015
March 18, 2023
Conditions
Outcome Measures
Primary Outcomes (3)
Incidence of grade 3 or higher treatment-related adverse event (AE) using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Treatment arms will be summarized reporting the number of patients treated; the number who experience grade 3 or higher treatment-related AE. In addition, number of treatment cycles received will be summarized using descriptive statistics (median and range) by treatment arm. Comprehensive safety data on all toxicities will be tabulated by type, grade, duration, attribution to treatment, and treatment arm. A patient level summary by worst grade toxicity will be included. Laboratory data and concomitant medications associated with episodes of toxicity will be summarized as needed.
Up to 30 days post-treatment
Proportion of patients with treatment-related dose limiting toxicities (DLT) using the National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Treatment arms will be summarized reporting the number of patients treated; the number who experience DLT; the number of patients who discontinue therapy, and the reasons for discontinuation. In addition, number of treatment cycles received will be summarized using descriptive statistics (median and range) by treatment arm. Comprehensive safety data on all toxicities will be tabulated by type, grade, duration, attribution to treatment, and treatment arm. A patient level summary by worst grade toxicity will be included.
21 days
Proportion of patients with treatment-related serious adverse events (SAEs) using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Treatment arms will be summarized reporting the number of patients treated; the number who experience SAEs. In addition, number of treatment cycles received will be summarized using descriptive statistics (median and range) by treatment arm. Comprehensive safety data on all toxicities will be tabulated by type, grade, duration, attribution to treatment, and treatment arm. A patient level summary by worst grade toxicity will be included. Laboratory data and concomitant medications associated with episodes of toxicity will be summarized as needed.
Up to 30 days post-treatment
Secondary Outcomes (9)
Best response complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Up to 4 years
Disease control rate (DCR)
Up to 4 years
Median overall survival (OS)
From randomization to death or date of censoring, assessed at 6 months
Median overall survival (OS)
From randomization to death or date of censoring, assessed at 12 months
Median progression-free survival (PFS) using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
From randomization until documented disease progression or death (by any cause, in the absence of progression), assessed at 6 months
- +4 more secondary outcomes
Study Arms (3)
Arm I (continuous selumetinib and paclitaxel)
EXPERIMENTALPatients receive selumetinib PO BID on days 1-21 and paclitaxel IV over a fixed rate on days 1 and 8.
Arm II (intermittent selumetinib and paclitaxel)
EXPERIMENTALPatients receive selumetinib PO BID on days 1-5, 8-12, and 15-19 and paclitaxel as in Arm I.
Arm III (pulsatile selumetinib and paclitaxel)
EXPERIMENTALPatients receive selumetinib PO BID on days 1-3, 8-10, and 15-17 and paclitaxel as in Arm I.
Interventions
Correlative studies
Given IV
Correlative studies
Given PO
Eligibility Criteria
You may qualify if:
- Histologically and/or cytologically confirmed, non-small cell lung cancer (NSCLC) of adenocarcinoma histology at the time of initial diagnosis.
- Mixed tumors will be categorized by the predominant cell type; (Note: If small cell elements are present the patient is ineligible)
- Known mutational status of KRAS and BRAF oncogenes.
- For patients in whom mutational testing result is unknown or unavailable from a prior test, KRAS and BRAF testing will be performed (at a Clinical Laboratory Improvement Act (CLIA) -certified laboratory) using an archived or fresh biopsy as per standard of care, prior to enrollment.
- Stage IIIB-IV, locally advanced or metastatic disease according to the 7th edition of the American Joint Committee on Cancer (AJCC) lung cancer Tumor, Node, Metastasis (TNM) classification system
- Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. Baseline measurements and evaluation of ALL sites of disease must be obtained within 4 weeks prior to enrollment.
- Failure of at least one line of systemic anti-cancer therapy for advanced NSCLC defined as either of the following:
- Radiological documentation of disease progression (or failure to achieve a response) or
- Discontinuation due to toxicity
- Prior treatment with immunotherapy as well as maintenance therapy, including both continuation and switch maintenance will be allowed if received at least 14 days before start date of selumetinib-paclitaxel (immunotherapy is not allowed within 14 days of the start date of selumetinib-paclitaxel).
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Estimated life expectancy, in the judgment of the investigator, which will permit receipt of treatment of 12 weeks or more
- Absolute neutrophil count \>= 1.5x10\^9 /L (1500 per mm\^3)
- Platelets \>= 100x10\^9 /L (100,000 per mm\^3)
- Hemoglobin \> 9.0 g/dL
- +13 more criteria
You may not qualify if:
- Known actionable mutations (e.g., EGFR, ALK, ROS1), against which there is available treatment. Patients who progressed on such treatment, i.e., have developed acquired resistance and are no longer reasonably expected to derive therapeutic benefit are eligible for the trial.
- Any prior treatment with either a MEK, RAS, or RAF inhibitor for advanced or metastatic NSCLC.
- A history of hypersensitivity to selumetinib, or any excipient agents (e.g. Captisol or TPGS- a water soluble form of vitamin E)
- Any unresolved toxicity \> Common Terminology Criteria for Adverse Events (CTCAE) grade 2 despite optimal care/support, from previous anti-cancer therapy, except for alopecia, within 7 days prior to cycle 1, day 1.
- Cardiac conditions as follows:
- Uncontrolled hypertension (Blood Pressure (BP) \>= 150/95 mmHg, despite medical therapy)
- Left ventricular ejection fraction (LVEF) \< 55%, measured by echocardiography
- Atrial fibrillation with a ventricular rate \> 100 bpm on electrocardiogram (ECG) at rest
- Symptomatic heart failure New York Heart Association (NYHA ) grade II-IV)
- Prior or current cardiomyopathy
- Severe valvular heart disease
- Uncontrolled angina (Canadian Cardiovascular Society grade II-IV despite medical therapy)
- Acute coronary syndrome within 6 months prior to starting treatment
- Ophthalmological conditions as follows:
- Intra-ocular pressure \> 21 mmHg, or uncontrolled glaucoma (irrespective of intra-ocular pressure)
- +8 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- OHSU Knight Cancer Institutelead
- Oregon Health and Science Universitycollaborator
- AstraZenecacollaborator
Study Sites (1)
OHSU Knight Cancer Institute
Portland, Oregon, 97239, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Brian Druker, MD
OHSU Knight Cancer Institute
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
July 14, 2015
First Posted
July 21, 2015
Study Start
July 21, 2016
Primary Completion
July 16, 2020
Study Completion
July 16, 2020
Last Updated
March 21, 2023
Record last verified: 2023-03