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

NCT02087241 | Terminated Phase 2 Results

• 1 other identifier: D6011C00002
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 8

Brief Summary

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

Conditions

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

Keywords

Stage IV Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  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 Outcomes (4)

• Assess the Objective Response Rates in Each Arm

  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

  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

  Up to a maximum of 4 treatment cycles (treatment cycles will be repeated every 21 days)

• Assess Overall Survival in Each Treatment Arm

  Up to a maximum of 4 treatment cycles (treatment cycles will be repeated every 21 days)

Study Arms (2)

AZD1775 + carboplatin + pemetrexed

EXPERIMENTAL

Randomised: AZD1775 + pemetrexed + carboplatin followed by maintenance AZD1775 + pemetrexed versus pemetrexed and carboplatin followed by maintenance pemetrexed.

Drug: AZD1775; Drug: pemetrexed; Drug: carboplatin

Placebo + carboplatin + pemetrexed

EXPERIMENTAL

Randomised: AZD1775 + pemetrexed + carboplatin followed by maintenance AZD1775 + pemetrexed versus pemetrexed and carboplatin followed by maintenance pemetrexed.

Drug: AZD1775 Matching Placebo; Drug: pemetrexed; Drug: carboplatin

Interventions

AZD1775 DRUG

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

Also known as: MK-1775

AZD1775 + carboplatin + pemetrexed

AZD1775 Matching Placebo DRUG

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

Placebo + carboplatin + pemetrexed

pemetrexed DRUG

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.

AZD1775 + carboplatin + pemetrexed; Placebo + carboplatin + pemetrexed

carboplatin DRUG

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.

AZD1775 + carboplatin + pemetrexed; Placebo + carboplatin + pemetrexed

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (8)

Research Site

Englewood, Colorado, United States

Location

Research Site

Fort Myers, Florida, United States

Location

Research Site

Orlando, Florida, United States

Location

Research Site

Peoria, Illinois, United States

Location

Research Site

Fort Wayne, Indiana, United States

Location

Research Site

Wichita, Kansas, United States

Location

Research Site

Cincinnati, Ohio, United States

Location

Research Site

Nashville, Tennessee, United States

Location

Related Publications (1)

• Johnson ML, Dakhil SR, Beck JT, Sadiq A, Menon S, Mugundu GM, Chmielecki J, Spigel DR. Two Phase II Trials of Adavosertib, a Wee1 Inhibitor with Docetaxel or Carboplatin plus Pemetrexed in Non-small-cell Lung Cancer. Target Oncol. 2025 Nov;20(6):967-978. doi: 10.1007/s11523-025-01177-x. Epub 2025 Nov 10.

  PMID: 41212474 DERIVED

MeSH Terms

Conditions

Lung Neoplasms

Interventions

adavosertib; Pemetrexed; Carboplatin

Condition Hierarchy (Ancestors)

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; Coordination Complexes; Organic Chemicals

Limitations and Caveats

The study was terminated on June 1, 2015 by the sponsor. The Primary Outcome Measure (Progression Free Survival) was not assessed and the randomised portion of the study was not done.

Results Point of Contact

• Title: Charles H. Davis
• Organization: SCRI Development Innovations

charles.davis2@scri-innovations.com

+615-524-4341

Study Officials

• David R Spigel, MD

  SCRI Development Innovations, LLC

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2014
• First Posted: March 14, 2014
• Study Start: March 1, 2014
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: March 29, 2017
• Results First Posted: March 29, 2017

Record last verified: 2017-02

Locations

US (8)