Ph II Trial of carboplatin and pemetrexed with or without AZD1775 for untreated lung cancer - None

Study identifier:D6011C00002

ClinicalTrials.gov identifier:NCT02087241

EudraCT identifier:N/A

CTIS identifier:N/A

Terminated/Withdrawn

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

Medical condition

Previously Untreated Stage IV Non-Squamous Non Small Cell Lung Cancer

Phase

Phase 2

Healthy volunteers

Study drug

AZD1775, AZD1775 Matching Placebo, pemetrexed, carboplatin

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years +

Date

Study Start Date: 01 Mar 2014

Primary Completion Date: 01 Jun 2015

Study Completion Date: 01 Jun 2015

Study design

Allocation: Randomized
Endpoint Classification: Safety/Efficacy
Intervention Model: Parallel Assignment
Masking: Double Blind
Primary Purpose: Treatment

Verification:

Verified 01 Feb 2017 by AstraZeneca

Collaborators

None

Inclusion and exclusion 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

No locations available

Arms	Assigned Interventions
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. Other Name: none 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. Other Name: none
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 Other Name: none 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. Other Name: none 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. Other Name: none

Arms

Assigned Interventions

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.

Other Name: none

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.

Other Name: none

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

Other Name: none

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.

Other Name: none

Documents available

Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]

Contact Backup

Cancer Study Locator

877 400 4656

[email protected]

Investigators

Principal Investigator

David R Spigel

Sarah Cannon Research Institute

Ph II Trial of carboplatin and pemetrexed with or without AZD1775 for untreated lung cancer - None

Official Title

Medical condition

Phase

Healthy volunteers

Study drug

Sex

Actual Enrollment

Study type

Age

Date

Study design

Verification:

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Documents available

Trial Results Summaries

Contacts

Contact

Contact Backup

Investigators

Principal Investigator