Clinical Trials Logo

Clinical Trial Details — Status: Not yet recruiting

Administrative data

NCT number NCT02972333
Other study ID # APOLLO
Secondary ID
Status Not yet recruiting
Phase Phase 3
First received November 16, 2016
Last updated November 20, 2016
Start date December 2016
Est. completion date December 2019

Study information

Verified date November 2016
Source Shandong Cancer Hospital and Institute
Contact Jinming Yu, MD.PhD.
Phone 0086-531-67626919
Email sdyujinming@163.com
Is FDA regulated No
Health authority China: Ministry of Health
Study type Interventional

Clinical Trial 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.


Description:

Patients with confirmed EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI and concurrent with brain metastasis will be enrolled into the study. All eligible patients will have access to AZD9291 regimen through the ASTRIS study as long as they continue to show clinical benefit.


Recruitment information / eligibility

Status Not yet recruiting
Enrollment 150
Est. completion date December 2019
Est. primary completion date September 2019
Accepts healthy volunteers No
Gender Both
Age group 18 Years and older
Eligibility Inclusion Criteria:

1. Provision of signed and dated written informed consent by the patient or legally acceptable representative prior to any study-specific procedures

2. Metastatic (stage IV) EGFRm NSCLC, not amenable to curative surgery or radiotherapy, with confirmation of the presence of the T790M mutation.

3. 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.

4. 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.

5. Prior therapy with an EGFR-TKI. Patients may have also received additional lines of treatment.

6. World Health Organization (WHO) performance status 0-2 with no deterioration over the previous 2 weeks and a minimum life expectancy of 3 months.

7. Adequate bone marrow reserve and organ function as demonstrated by complete blood count, biochemistry in blood and urine at baseline.

8. ECG recording at baseline showing absence of any cardiac abnormality as per exclusion criterion #10.

9. 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:

1. Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments

2. 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

3. Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation

10. Male patients must be willing to use barrier contraception, i.e., condoms.

Exclusion Criteria:

Subjects should not enter the study if any of the following exclusion criteria are fulfilled:

1. Previous (within 6 months) or current treatment with AZD9291

2. 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)

3. 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.

4. 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.

5. Prior whole brain radiation therapy.

6. Known intracranial hemorrhage which is unrelated to tumor.

7. For patients with LM and/or BM, CNS complications that require urgent neurosurgical intervention (e.g. resection or shunt placement).

8. For patients with LM, inability to undergo collection of CSF.

9. Past medical history of ILD, drug-induced ILD, radiation pneumonitis requiring steroid treatment, or any evidence of clinically active ILD

10. Any of the following cardiac criteria:

1. Mean resting corrected QT interval (QTcF) > 470 ms using Fredericia's formula :

2. 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)

3. Any factors that increase the risk of QTc prolongation or risk of arrhythmic events

11. Any unresolved toxicity from prior therapy CTCAE > grade 3 at the time of starting treatment

12. History of hypersensitivity to excipients of AZD9291 or to drugs with a similar chemical structure or class to AZD9291

13. Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:

- Absolute neutrophil count < 1.5 x 10^9/L

- Platelet count < 100 x 10^9/L

- Haemoglobin < 90 g/L

- Alanine aminotransferase > 2.5 times the upper limit of normal (ULN) if no demonstrable liver metastases or > 5 times ULN in the presence of liver metastases

- Aspartate aminotransferase > 2.5 times ULN if no demonstrable liver metastases or > 5 times ULN in the presence of liver metastases

- Total bilirubin > 1.5 times ULN. Total bilirubin >3 times the ULN in patients with documented Gilbert's Syndrome (unconjugated hyperbilirubinaemia) or in the presence of liver metastases

- Creatinine >1.5 times ULN concurrent with creatinine clearance < 50 mL/min (measured or calculated by Cockcroft and Gault equation). Confirmation of creatinine clearance is only required when creatinine is >1.5 times ULN.

- If bone metastases are present and liver function is otherwise considered adequate by the investigator then elevated ALP will not exclude the patient.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment


Intervention

Drug:
AZD9291 80mg oral each day
All eligible patients will have access to AZD9291 regimen through the ASTRIS study as long as they continue to show clinical benefit.
Radiation:
Radiation therapy
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.

Locations

Country Name City State
n/a

Sponsors (2)

Lead Sponsor Collaborator
Shandong Cancer Hospital and Institute AstraZeneca

Outcome

Type Measure Description Time frame Safety issue
Other T790M mutation positive rate To investigate the effect of AZD9291 on the inhibition of proof of mechanism biomarkers (to include, but not limited to EGFR T790M) in cell pellets from pre- and post-treatment CSF samples in comparison with blood samples. 2 years No
Other Concordance of T790M status between CSF and plasma To investigate the effect of AZD9291 on the inhibition of proof of mechanism biomarkers (to include, but not limited to EGFR T790M) in cell pellets from pre- and post-treatment CSF samples in comparison with blood samples. 2 years No
Other Change of imputed ctDNA concentration before and after treatment To investigate the effect of AZD9291 on the inhibition of proof of mechanism biomarkers (to include, but not limited to EGFR T790M) in cell pellets from pre- and post-treatment CSF samples in comparison with blood samples. 2 years No
Other Proportion of each genetic mutation To investigate the effect of AZD9291 on the inhibition of proof of mechanism biomarkers (to include, but not limited to EGFR T790M) in cell pellets from pre- and post-treatment CSF samples in comparison with blood samples. 2 years No
Other Change from baseline in glucose and protein levels To evaluate the changes from baseline in CSF biochemistry to support the demonstration of the anti-tumour effect of AZD9291 in addition to CSF cytology. 2 years No
Other Change from baseline in tumor cell count To evaluate the changes from baseline in CSF biochemistry to support the demonstration of the anti-tumour effect of AZD9291 in addition to CSF cytology. 2 years No
Other AZD9291 concentration level in CSF/plasma To explore potential relation between relevant efficacy measures, biomarkers or safety variables and plasma or CSF concentration of AZD9291 (or metabolites). 2 years No
Primary 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 No
Secondary PFSe (extracranial progression-free survival) To further assess the efficacy of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI in pre-specified patient subgroups, e.g. AZD9291 single regimen, AZD9291 (before or after radiotherapy) with radiotherapy etc. 2 years No
Secondary PFSi (intracranial progression-free survival) To further assess the efficacy of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI in pre-specified patient subgroups, e.g. AZD9291 single regimen, AZD9291 (before or after radiotherapy) with radiotherapy etc. 2 years No
Secondary ORRo (overall objective response rate) To further assess the efficacy of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI in pre-specified patient subgroups, e.g. AZD9291 single regimen, AZD9291 (before or after radiotherapy) with radiotherapy etc. 2 years No
Secondary ORRe (extracranial objective response rate) To further assess the efficacy of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI in pre-specified patient subgroups, e.g. AZD9291 single regimen, AZD9291 (before or after radiotherapy) with radiotherapy etc. 2 years No
Secondary ORRi (intracranial objective response rate) To further assess the efficacy of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI in pre-specified patient subgroups, e.g. AZD9291 single regimen, AZD9291 (before or after radiotherapy) with radiotherapy etc. 2 years No
Secondary DCRo (overall disease control rate) To further assess the efficacy of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI in pre-specified patient subgroups, e.g. AZD9291 single regimen, AZD9291 (before or after radiotherapy) with radiotherapy etc. 2 years No
Secondary DCRe (extracranial disease control rate) To further assess the efficacy of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI in pre-specified patient subgroups, e.g. AZD9291 single regimen, AZD9291 (before or after radiotherapy) with radiotherapy etc. 2 years No
Secondary DCRi (intracranial disease control rate) To further assess the efficacy of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI in pre-specified patient subgroups, e.g. AZD9291 single regimen, AZD9291 (before or after radiotherapy) with radiotherapy etc. 2 years No
Secondary DoRo (overall duration of response) To further assess the efficacy of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI in pre-specified patient subgroups, e.g. AZD9291 single regimen, AZD9291 (before or after radiotherapy) with radiotherapy etc. 3 years No
Secondary DoRe (extracranial duration of response) To further assess the efficacy of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI in pre-specified patient subgroups, e.g. AZD9291 single regimen, AZD9291 (before or after radiotherapy) with radiotherapy etc. 2 years No
Secondary DoRi (intracranial duration of response) To further assess the efficacy of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI in pre-specified patient subgroups, e.g. AZD9291 single regimen, AZD9291 (before or after radiotherapy) with radiotherapy etc. 2 years No
Secondary OS(overall survival) To further assess the efficacy of AZD9291 in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI in pre-specified patient subgroups, e.g. AZD9291 single regimen, AZD9291 (before or after radiotherapy) with radiotherapy etc. 3 years No
Secondary Adverse events/Serious adverse events To evaluate the safety and tolerability profile of AZD9291 and subgroups such as AZD9291 single regimen, AZD9291(before or after radiotherapy) with radiotherapy and etc. in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI. 2 years Yes
Secondary QoL To assess disease-related symptoms and QoL in overall population as well as in pre-specified subgroups, e.g. AZD9291 single regimen, AZD9291(before or after radiotherapy) with radiotherapy etc. in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI. 2 years Yes
Secondary Cognitive function To assess disease-related symptoms and cognitive function in overall population as well as in pre-specified subgroups, e.g. AZD9291 single regimen, AZD9291(before or after radiotherapy) with radiotherapy etc. in brain metastases from patients with EGFR T790M positive NSCLC who have received prior therapy with an EGFR-TKI. 2 years Yes
See also
  Status Clinical Trial Phase
Active, not recruiting NCT04074096 - Binimetinib Encorafenib Pembrolizumab +/- Stereotactic Radiosurgery in BRAFV600 Melanoma With Brain Metastasis Phase 2
Recruiting NCT04474925 - Pre- Versus Post-operative SRS for Resectable Brain Metastases Phase 3
Recruiting NCT05358340 - Dual Perfusion Imaging for Characterizing Vascular Architecture of Brain Lesions N/A
Recruiting NCT05559853 - Developing a New MRI Technique to Understand Changes in Brain Tumors After Treatment
Completed NCT03189381 - Pilot Phase 2 Study Whole Brain Radiation Therapy With Simultaneous Integrated Boost for Patients With Brain Metastases N/A
Completed NCT02082587 - Toronto BNB Pilot Study N/A
Terminated NCT01551680 - A Trial Evaluating Concurrent Whole Brain Radiotherapy and Iniparib in Multiple Non Operable Brain Metastases Phase 1
Terminated NCT00717275 - Study of Temozolomide to Treat Newly Diagnosed Brain Metastases Phase 2
Recruiting NCT05048212 - A Phase II Study of Nivolumab With Ipilimumab and Cabozantinib in Patients With Untreated Renal Cell Carcinoma Brain Metastases Phase 2
Recruiting NCT03714243 - Blood Brain Barrier Disruption (BBBD) Using MRgFUS in the Treatment of Her2-positive Breast Cancer Brain Metastases N/A
Recruiting NCT05573815 - Evaluation of Clinical Decision Support System for Brain Metastasis Using Brain MR Images N/A
Recruiting NCT04899908 - Stereotactic Brain-directed Radiation With or Without Aguix Gadolinium-Based Nanoparticles in Brain Metastases Phase 2
Completed NCT04507217 - Tislelizumab Combined With Pemetrexed/ Carboplatin in Patients With Brain Metastases of Non-squamous NSCLC Phase 2
Recruiting NCT05452005 - Fluorine-18-AlphaVBeta6-Binding Peptide Positron Emission Tomography in Metastatic Non-Small Cell Lung Cancer Phase 1
Recruiting NCT06457906 - SRS/SRT/Hypo-RT Versus HA-WBRT for No More Than 10 Brain Metastases in SCLC Phase 3
Completed NCT04170777 - Perfexion Registration Using CBCT
Recruiting NCT03027544 - Tomotherapy for Refractory Brain Metastases N/A
Completed NCT04178330 - Tomotherapy as Primary Radiotherapy for Multipule Brain Metastases N/A
Terminated NCT02187822 - Fractionated Stereotactic Radiotherapy (FSRT) in Treatment of Brain Metastases Phase 1
Terminated NCT00538343 - RTA 744 in Breast Cancer Patients With Progression of Previously Irradiated Brain Metastases Phase 2