Phase II Study of AZD9291 in Advanced Stage NSCLC With EGFR and T790M Mutations Detected in Plasma Ct-DNA

NCT02811354 | Unknown Phase 2 DMC

• 2 other identifiers: ESR-15-109322015/01069
• Study Type: interventional
• Target: 108
• Locations: 5 countries
• Sites: 8

Brief Summary

Circulating tumor DNA (ctDNA) is a highly specific and effective biomarker for the detection of EGFR mutation status. We hypothesise AZD9291 is efficacious in patients with EGFR sensitizing mutations and T790M detected in plasma ctDNA. This is a prospective, open label, multi-centre single arm phase II study assessing the efficacy and safety of AZD9291 monotherapy in patients with stage IIIB or IV harboring sensitising EGFR mutation (exon 19 deletions or exon 21 L858R substitution mutations) and T790M who have progressed following prior treatment with an approved EGFR TKI. Approximately 106 subjects will be enrolled. All patients must have documented radiological progression on EGFR-TKI treatment and on the last treatment administered prior to enrolling in the study.

Conditions

Carcinoma, Non-Small-Cell Lung

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  From the time of their first treatment with daily AZD9291 till 28 days after discontinuation

Secondary Outcomes (5)

• Progression free survival (PFS)

  From the time of their first treatment with daily AZD9291 till 28 days after discontinuation

• Duration of response (DoR)

  From the time of their first treatment with daily AZD9291 till 28 days after discontinuation

• Disease control rate (DCR)

  From the time of their first treatment with daily AZD9291 till 28 days after discontinuation

• Tumour shrinkage

  From the time of their first treatment with daily AZD9291 till 28 days after discontinuation

• Overall survival (OS)

  From the time of their first treatment with daily AZD9291 till 28 days after discontinuation

Study Arms (1)

AZD9291

EXPERIMENTAL

Patient will be treated with AZD9291 at a starting dose of 80mg once a day until the patient completes the study, withdraws from the study or closure of the study. A cycle of treatment is defined as 28 days of once daily AZD9291 treatment. Patients may continue to receive AZD9291 until objective disease progression (determined by RECIST 1.1) or if the subject is no longer receiving clinical benefit in the Investigator's opinion.

Drug: AZD9291

Interventions

AZD9291 DRUG

oral administration as a single daily dose of 80 mg

Also known as: Osimertinib

AZD9291

Eligibility Criteria

• Age: 21 Years - 99 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
• Patients must be \>= 21 years of age.
• Locally advanced/metastatic NSCLC not amenable to curative surgery or radiotherapy
• Documentation of activating EGFR mutations (exon 19 deletions or exon 21 L858R substitution mutations) at the time of initial diagnosis
• Radiological documentation of disease progression: following 1st line EGFR TKI treatment but who have not received further treatment OR following prior therapy with an EGFR TKI and a platinum-based doublet chemotherapy. All patients must have documented radiological progression on the last treatment administered prior to enrolling in the study.
• Patient may receive up to two lines of therapies (including EGFR TKI).
• Plasma sample must harbour an EGFR mutation known to be associated with EGFR TKI sensitivity (exon 19 deletion, L858R). Confirmation of T790M status by central lab testing from a plasma sample taken after confirmation of disease progression on the most recent treatment regimen.
• Patients must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below:
• Haemoglobin \>= 10.0 g/dL and no blood transfusions in the 28 days prior to entry
• Absolute neutrophil count (ANC) \>= 1.5 x 109/L
• No features suggestive of MDS/AML on peripheral blood smear
• White blood cells (WBC) \> 3x109/L
• Platelet count \>= 100 x 109/L
• Total bilirubin \<= 1.5 x institutional upper limit of normal (ULN)
• AST (SGOT)/ALT (SGPT) \<= 2.5 x institutional upper limit of normal unless liver metastases are present in which case it must be \<= 5x ULN

You may not qualify if:

• Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
• Treatment with an EGFR-TKI within 8 days of study entry; any cytotoxic chemotherapy, or other anticancer drugs within 21 days of study entry
• Treatment with an investigational drug within five half-lives of the compound
• Prior treatment with an immune checkpoint inhibitor
• Previous treatment with AZD9291 (or 3rd generation EGFR TKIs)
• Patients with second primary cancer, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for \>= 5 years
• Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks
• The patient may receive bisphosphonates for the treatment of bone metastases.
• Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of starting study treatment with the exception of alopecia and grade 2, prior platinum-therapy related neuropathy.
• Unstable spinal cord compression/brain metastases unless asymptomatic, stable and not requiring steroids for at least 2 weeks prior to start of study treatment.
• Major surgery within 4 weeks of starting study treatment and patients must have recovered from any effects of any major surgery.
• Patients currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be potent inhibitors of CYP3A4 (at least 1 week prior) and potent inducers of CYP3A4 (at least 3 week prior) (Appendix A). All patients must try to avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer/inhibitory effects on CYP3A4.
• Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardise compliance with the protocol, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required.
• Past medical history of ILD, drug-induced ILD, radiation pneumonitis requiring steroid treatment, or any evidence of clinically active ILD
• Any of the following cardiac criteria:

Sponsors & Collaborators

• National University Hospital, Singapore: lead
• AstraZeneca: collaborator
• Singapore Clinical Research Institute: collaborator

Study Sites (8)

Pamela Youde Nethersole Eastern Hospital

Chai Wan, Hong Kong

RECRUITING

Prince of Wales Hospital

Shatin, Hong Kong

RECRUITING

National University Hospital

Singapore, 164119, Singapore

RECRUITING

Samsung Medical Center Sungkyunkwan University

Irwon-dong, Seoul, South Korea

RECRUITING

Yonsei Cancer Center

Sinchon-dong, Seoul, South Korea

RECRUITING

Seoul National University College of Medicine

Yeongeon-dong, Seoul, 03080, South Korea

RECRUITING

National Taiwan University Hospital

Taipei, 10002, Taiwan

RECRUITING

Ramathibodi Hospital

Bangkok, 10400, Thailand

RECRUITING

Related Publications (2)

• Jiang T, Zhou C. Clinical activity of the mutant-selective EGFR inhibitor AZD9291 in patients with EGFR inhibitor-resistant non-small cell lung cancer. Transl Lung Cancer Res. 2014 Dec;3(6):370-2. doi: 10.3978/j.issn.2218-6751.2014.08.02.

  PMID: 25806323 BACKGROUND

• Cross DA, Ashton SE, Ghiorghiu S, Eberlein C, Nebhan CA, Spitzler PJ, Orme JP, Finlay MR, Ward RA, Mellor MJ, Hughes G, Rahi A, Jacobs VN, Red Brewer M, Ichihara E, Sun J, Jin H, Ballard P, Al-Kadhimi K, Rowlinson R, Klinowska T, Richmond GH, Cantarini M, Kim DW, Ranson MR, Pao W. AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov. 2014 Sep;4(9):1046-61. doi: 10.1158/2159-8290.CD-14-0337. Epub 2014 Jun 3.

  PMID: 24893891 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

osimertinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Ross Soo

  National University Hospital, Singapore

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ross Soo

CONTACT

(65) 6779 5555; ross_soo@nuhs.edu.sg

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 21, 2016
• First Posted: June 23, 2016
• Study Start: February 24, 2017
• Primary Completion: February 24, 2019
• Study Completion: February 24, 2020
• Last Updated: September 20, 2018

Record last verified: 2018-09

Locations

TH (1); KR (3); TW (1); HK (2); SG (1)