Open Label, Prospective Study to Investigate Efficacy and Safety of AZD9291 in BM From NSCLC Patients With EGFR T790M

NCT02972333 | Unknown Phase 3 DMC

• 1 other identifier: APOLLO
• Study Type: interventional
• Target: 150
• Locations: 0 countries
• Sites: N/A

Brief Summary

The study aims to investigate the efficacy and safety of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI.

Conditions

EGFR-TKI Resistant Mutation; Nonsmall Cell Lung Cancer; AZD9291; Brain Metastases

Outcome Measures

Primary Outcomes (1)

• PFSo (overall progression free survival)

  To assess the efficacy of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI by PFSo

  2 years

Secondary Outcomes (15)

• PFSe (extracranial progression-free survival)

  2 years

• PFSi (intracranial progression-free survival)

  2 years

• ORRo (overall objective response rate)

  2 years

• ORRe (extracranial objective response rate)

  2 years

• ORRi (intracranial objective response rate)

  2 years

Other Outcomes (7)

• T790M mutation positive rate

  2 years

• Concordance of T790M status between CSF and plasma

  2 years

• Change of imputed ctDNA concentration before and after treatment

  2 years

Study Arms (1)

AZD9291 80mg oral each day±RT

EXPERIMENTAL

AZD9291(80mg, QD, p.o.) was provided to patients with confirmed EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI and concurrent with brain metastasis. Radiation therapy will be implemented according to investigator's clinical practice(A 7-10 days washout period before radiotherapy and 1 week period after completion of brain radiothearpy before re-starting AZD9291.).

Drug: AZD9291 80mg oral each day; Radiation: Radiation therapy

Interventions

AZD9291 80mg oral each day DRUG

All eligible patients will have access to AZD9291 regimen through the ASTRIS study as long as they continue to show clinical benefit.

Also known as: AZD9291, 80mg, QD, p.o. (2nd line or later)

AZD9291 80mg oral each day±RT

Radiation therapy RADIATION

Radiation therapy will be implemented according to investigator's clinical practice.Based on the guidelines provided for the interruption of ADZ9291 with brain radiation therapy, a 7-10 days washout period before radiotherapy and 1 week period after completion of brain radiothearpy before re-starting AZD9291.

Also known as: WBRT or SRS

AZD9291 80mg oral each day±RT

Eligibility Criteria

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

You may qualify if:

• Provision of signed and dated written informed consent by the patient or legally acceptable representative prior to any study-specific procedures
• Metastatic (stage IV) EGFRm NSCLC, not amenable to curative surgery or radiotherapy, with confirmation of the presence of the T790M mutation.
• For patients with LM: Confirmed diagnosis of LM by positive CSF cytology. Diagnosis by MRI only is not eligible for study entry. At least one site of CNS leptomeningeal disease that can be assessed by magnetic resonance imaging (MRI) and which is suitable for repeat assessments. Measurable CNS or extracranial disease is not required.
• For patients with measurable BM but without LM: At least one measurable intracranial lesion that, if previously irradiated, has progressed or not responded to radiation therapy, that can be accurately measured at baseline as ≥ 10 mm in the longest diameter by magnetic resonance imaging (MRI) and which is suitable for accurate repeated measurements. Measurable extracranial disease is not required.
• Prior therapy with an EGFR-TKI. Patients may have also received additional lines of treatment.
• World Health Organization (WHO) performance status 0-2 with no deterioration over the previous 2 weeks and a minimum life expectancy of 3 months.
• Adequate bone marrow reserve and organ function as demonstrated by complete blood count, biochemistry in blood and urine at baseline.
• Female patients of childbearing potential must be using adequate contraceptive measures (see Restrictions, Section 3.5), must not be breast feeding, and must have a negative pregnancy test prior to start of dosing. Otherwise, they must have evidence of nonchild bearing potential as defined below:
• Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments
• Women less than 50 years would be consider post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution
• Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation
• Male patients must be willing to use barrier contraception, i.e., condoms.

You may not qualify if:

• Previous (within 6 months) or current treatment with AZD9291
• Patients currently receiving (or unable to stop use at least 1 week prior to receiving the first dose of AZD9291) any treatment known to be potent inhibitors or inducers of cytochrome P450 (CYP) 3A4 (Appendix B)
• Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, active bleeding diatheses, active infection\* including hepatitis B, hepatitis C and human immunodeficiency virus, or significantly impaired bone marrow reserve or organ function, including hepatic and renal impairment, which in the investigator's opinion would significantly alter the risk/benefit balance.
• \* active infection will include any patients receiving intravenous treatment for any infection and patients with hepatitis B or C surface antigen (+) - Patients receiving oral antiviral suppressive therapy for hepatitis B or C will be permitted to enrol in the study.
• Patient with symptomatic central nervous system (CNS) metastases who is neurologically unstable or has required increasing doses of steroids to manage CNS symptoms within the 2 weeks prior to start AZD9291 administration.
• Prior whole brain radiation therapy.
• Known intracranial hemorrhage which is unrelated to tumor.
• For patients with LM and/or BM, CNS complications that require urgent neurosurgical intervention (e.g. resection or shunt placement).
• For patients with LM, inability to undergo collection of CSF.
• 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:
• Mean resting corrected QT interval (QTcF) \> 470 ms using Fredericia's formula :
• Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block)
• Any factors that increase the risk of QTc prolongation or risk of arrhythmic events
• Any unresolved toxicity from prior therapy CTCAE \> grade 3 at the time of starting treatment

Sponsors & Collaborators

• Shandong Cancer Hospital and Institute: lead
• AstraZeneca: collaborator

Related Publications (1)

• Xing L, Pan Y, Shi Y, Shu Y, Feng J, Li W, Cao L, Wang L, Gu W, Song Y, Xing P, Liu Y, Gao W, Cui J, Hu N, Li R, Bao H, Shao Y, Yu J. Biomarkers of Osimertinib Response in Patients with Refractory, EGFR-T790M-positive Non-Small Cell Lung Cancer and Central Nervous System Metastases: The APOLLO Study. Clin Cancer Res. 2020 Dec 1;26(23):6168-6175. doi: 10.1158/1078-0432.CCR-20-2081. Epub 2020 Aug 17.

  PMID: 32817079 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Brain Neoplasms

Interventions

osimertinib; Radiotherapy; Spermine Synthase

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Alkyl and Aryl Transferases; Transferases; Enzymes; Enzymes and Coenzymes

Study Officials

• Jinming Yu, MD.PhD.

  Shandong Cancer Hospital and Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jinming Yu, MD.PhD.

CONTACT

0086-531-67626919; sdyujinming@163.com

Ligang Xing, MD.PhD.

CONTACT

0086-531-67626819; xinglg@medmail.com.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dean

Study Record Dates

• First Submitted: November 16, 2016
• First Posted: November 23, 2016
• Study Start: December 1, 2016
• Primary Completion: September 1, 2019
• Study Completion: December 1, 2019
• Last Updated: November 23, 2016

Record last verified: 2016-11

Data Sharing

• IPD Sharing: Will not share