Ph II Trial of Carboplatin and Pemetrexed With or Without AZD1775 for Untreated Lung Cancer

February 10, 2017 updated by: AstraZeneca

A Phase II Study of AZD1775 Plus Pemetrexed and Carboplatin Followed by a Randomised Comparison of Pemetrexed and Carboplatin With or Without AZD1775 in Patients With Previously Untreated Stage IV Non-Squamous Non-Small-Cell Lung Cancer

The aim of this study is to combine AZD1775 with standard front-line chemotherapy in subjects with advanced NSCLC.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a randomised, phase II trial comparing AZD1775 plus pemetrexed and carboplatin followed by maintenance AZD1775 and pemetrexed versus pemetrexed and carboplatin followed by maintenance pemetrexed in patients with previously untreated metastatic non-squamous NSCLC with TP53 mutations. The primary endpoint of the trial is assessment of progression-free survival (PFS).

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
22

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Colorado
      • Englewood, Colorado, United States
        • Research Site
    • Florida
      • Fort Myers, Florida, United States
        • Research Site
      • Orlando, Florida, United States
        • Research Site
    • Illinois
      • Peoria, Illinois, United States
        • Research Site
    • Indiana
      • Fort Wayne, Indiana, United States
        • Research Site
    • Kansas
      • Wichita, Kansas, United States
        • Research Site
    • Ohio
      • Cincinnati, Ohio, United States
        • Research Site
    • Tennessee
      • Nashville, Tennessee, United States
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria

  • Provision of informed consent prior to any study specific procedures
  • Histologic or cytologic diagnosis of advanced NSCLC, Recurrent or Stage IV disease (according to American Joint Committee on Cancer (AJCC) staging system, v7.0).
  • No prior chemotherapy for locally advanced or metastatic disease
  • Subjects with a known EGFR mutation must have received previous treatment with an EGFR tyrosine kinase inhibitor; and subjects with a known ALK translocation must have received previous treatment with an ALK inhibitor.
  • No prior radiation therapy to the whole pelvis or to ≥25% of the total bone marrow area.
  • At least one measurable lesion according to Response Evaluation Criteria in Solid Tumours (RECIST) v1.1
  • Mandatory availability of tumour tissue (archival or fresh if archival is not available) for TP53 determination.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 or 1.
  • Absolute neutrophil count (ANC) ≥1500/μL
  • Hemoglobin (Hgb) ≥10 g/dL
  • Platelets ≥100,000/μL
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST), ≤3.0 x the upper limit of normal (ULN); 5 x ULN if known hepatic metastases
  • Total bilirubin ≤1.5 x ULN, unless secondary to Gilbert's disease
  • Serum creatinine ≤1.5 x ULN and a calculate creatinine clearance (CrCl) ≥45 mL/min by the Cockcroft-Gault method
  • Ability to swallow oral medication
  • Fertile male subjects willing to use at least one medically acceptable form of birth control for the duration of the study and for 2 weeks after treatment stops
  • Female subjects who are not of childbearing potential and fertile female subjects of childbearing potential who agree to use adequate contraceptive measures who are not breastfeeding, and who have a negative serum or urine pregnancy test within 72 hours prior to start of study treatment
  • Predicted life expectancy ≥12 weeks
  • Must be ≥18 years of age
  • Willingness and ability to comply with study and follow-up procedures
  • Ability to understand the nature of this trial and give written informed consent Exclusion criteria
  • Use of a study drug ≤21 days or 5 half-lives (whichever is shorter) prior to the first dose of AZD1775
  • Major surgical procedures ≤28 days of beginning AZD1775, or minor surgical procedures ≤7 days
  • Known central nervous system (CNS) disease
  • Subject has had prescription or non-prescription drugs or other products (i.e. grapefruit juice) known to be sensitive CYP3A4 substrates
  • Any known hypersensitivity or contraindication to the components of study treatment
  • Any of the following cardiac diseases currently or within the last 6 months as defined by New York Heart Association ([NYHA] Appendix G) ≥ Class 2
  • Corrected QT interval (QTc) >470 msec (as calculated by Fridericia correction formula) at study entry or congenital long QT syndrome.
  • Pregnant or lactating
  • Any serious, active underlying medical condition that would impair the ability of the subjects to receive study treatment
  • Unable or unwilling to take folic acid or vitamin B12
  • Presence of other active cancers, or history of treatment for invasive cancer ≤3 years
  • Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: AZD1775 + carboplatin + pemetrexed
Randomised: AZD1775 + pemetrexed + carboplatin followed by maintenance AZD1775 + pemetrexed versus pemetrexed and carboplatin followed by maintenance pemetrexed.
Drug: AZD1775
AZD1775 is a highly selective, adenosine-triphosphate (ATP) competitive, small molecule inhibitor of the WEE 1 kinase that sensitizes tumor cells to cytotoxic agents and is being developed for the treatment of advanced solid tumors and p53 pathway deficient malignancies
Other Names:
  • MK-1775
Drug: pemetrexed
This drug is a part of a general group of chemotherapy drugs called anti-metabolites. It prevents cells from using folate to make DNA and RNA. Because cancer cells need these substances to make new cells, this drug helps to stop the growth of cancer cells.
Drug: carboplatin
This drug is a platinum chemotherapy drug that acts like an alkylating agent. It stops the growth of cancer cells, causing the cells to die.
Experimental: Placebo + carboplatin + pemetrexed
Randomised: AZD1775 + pemetrexed + carboplatin followed by maintenance AZD1775 + pemetrexed versus pemetrexed and carboplatin followed by maintenance pemetrexed.
Drug: pemetrexed
This drug is a part of a general group of chemotherapy drugs called anti-metabolites. It prevents cells from using folate to make DNA and RNA. Because cancer cells need these substances to make new cells, this drug helps to stop the growth of cancer cells.
Drug: carboplatin
This drug is a platinum chemotherapy drug that acts like an alkylating agent. It stops the growth of cancer cells, causing the cells to die.
Drug: AZD1775 Matching Placebo
AZD1775 is a highly selective, adenosine-triphosphate (ATP) competitive, small molecule inhibitor of the WEE 1 kinase that sensitizes tumor cells to cytotoxic agents and is being developed for the treatment of advanced solid tumors and p53 pathway deficient malignancies

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Progression Free Survival
Time Frame: 6 months
Progression free survival is defined as the time from randomisation until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the subject withdraws from randomised therapy or receives another anti-cancer therapy prior to progression.
6 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Assess the Objective Response Rates in Each Arm
Time Frame: Up to a maximum of 4 treatment cycles (treatment cycles will be repeated every 21 days)
The objective response rate is defined as the number of the subjects with a confirmed best overall response of CR or PR divided by the number of subjects in the Full Analysis Set (FAS) for whom measureable disease is present at baseline
Up to a maximum of 4 treatment cycles (treatment cycles will be repeated every 21 days)
Assess the Disease Control Rate in Each Treatment Arm
Time Frame: Up to a maximum of 4 treatment cycles (treatment cycles will be repeated every 21 days)
the disease control rate is defined as the percentage of FAS subjects with a best overall response of CR, PR or SD).
Up to a maximum of 4 treatment cycles (treatment cycles will be repeated every 21 days)
Assess the Duration of Response in Each Treatment Arm
Time Frame: Up to a maximum of 4 treatment cycles (treatment cycles will be repeated every 21 days)
Duration of response is defined as the time from the date of first documented response until the date of documented progression or any cause death.
Up to a maximum of 4 treatment cycles (treatment cycles will be repeated every 21 days)
Assess Overall Survival in Each Treatment Arm
Time Frame: Up to a maximum of 4 treatment cycles (treatment cycles will be repeated every 21 days)
Overall survival is defined as the time from the date of randomization until death due to any cause.
Up to a maximum of 4 treatment cycles (treatment cycles will be repeated every 21 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
AstraZeneca

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: David R Spigel, MD, SCRI Development Innovations, LLC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2015

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 6, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 12, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 14, 2014

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 29, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 10, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • D6011C00002

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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