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

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ClinicalTrials.gov Identifier: NCT02087241
Recruitment Status : Terminated (The sponsor decided to terminate the study.)
First Posted : March 14, 2014
Results First Posted : March 29, 2017
Last Update Posted : March 29, 2017
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

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

Condition or disease Intervention/treatment Phase
Previously Untreated Stage IV Non-Squamous Non Small Cell Lung Cancer Drug: AZD1775 Drug: AZD1775 Matching Placebo Drug: pemetrexed Drug: carboplatin Phase 2

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).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 22 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : March 2014
Actual Primary Completion Date : June 2015
Actual Study Completion Date : June 2015

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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 Name: 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: 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

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.




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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

  2. 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).

  3. 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.

  4. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02087241


Locations
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United States, Colorado
Research Site
Englewood, Colorado, United States
United States, Florida
Research Site
Fort Myers, Florida, United States
Research Site
Orlando, Florida, United States
United States, Illinois
Research Site
Peoria, Illinois, United States
United States, Indiana
Research Site
Fort Wayne, Indiana, United States
United States, Kansas
Research Site
Wichita, Kansas, United States
United States, Ohio
Research Site
Cincinnati, Ohio, United States
United States, Tennessee
Research Site
Nashville, Tennessee, United States
Sponsors and Collaborators
AstraZeneca
Investigators
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Principal Investigator: David R Spigel, MD SCRI Development Innovations, LLC
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02087241    
Other Study ID Numbers: D6011C00002
First Posted: March 14, 2014    Key Record Dates
Results First Posted: March 29, 2017
Last Update Posted: March 29, 2017
Last Verified: February 2017
Keywords provided by AstraZeneca:
Stage IV Lung Cancer
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Carboplatin
Pemetrexed
MK-1775
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors