To Evaluate the Efficacy/Safety of Osimertinib Prior to CRT and Maintenance of it With Stage III, Unresectable NSCLC With EGFR Mutations

Lung Cancer Clinical Trial

— NEOLA  

Official title:

A Phase II, Open-label, Single-arm Study of Osimertinib as Induction Therapy Prior to CRT and Maintenance Osimertinib in Patients With Epidermal Growth Factor Receptor (EGFR) Mutation-positive, Stage III, Unresectable Non-small Cell Lung Cancer (NEOLA)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06194448
• Other study ID #: D516AC00003
• Secondary ID: 2023-507798-16-0
• Status: Recruiting
• Phase: Phase 2
• Start date: April 21, 2024
• Est. completion date: March 31, 2028

Study information

• Verified date: June 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to measure efficacy and safety of osimertinib as induction therapy prior to curative intent CRT and maintenance osimertinib in adult patients with Stage III, unresectable NSCLC with common EGFR mutations (exon 19 deletion or L858R).

Description:

The study duration will be approximately 2 years for recruitment and 2 years of follow-up from the last patient's initiation into the study.

The induction treatment with osimertinib will be up to 8 weeks, followed by 6 weeks of CRT treatment and osimertinib maintenance treatment until PD or death.

The visit frequency will be every 2 weeks to 4 weeks during the induction treatment period, every 3 weeks during the CRT period (every 3 weeks for chemotherapy and daily visits for RT)), and every 12 weeks during the osimertinib maintenance treatment period.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 70
• Est. completion date: March 31, 2028
• Est. primary completion date: April 28, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 130 Years

Eligibility

Inclusion Criteria:

1. Patients must be 18 or the legal age of consent in the jurisdiction in which the study is taking place, at the time of signing the informed consent form.

2. Patients with histologically documented NSCLC of predominantly non-squamous, squamous, and adenosquamous pathology who present with locally advanced, unresectable (Stage III) disease (according to Version 8 of the IASLC Staging Manual in Thoracic Oncology). It is recommended but not required that except for overt cT4 disease, nodal status N2, or N3 should have been proven by biopsy, via endobronchial ultrasound, mediastinoscopy, thoracoscopy, or in absence of biopsy, should have been confirmed with whole body 18FDG PET plus contrast-enhanced CT in addition to or in combination with PET.

3. Patient who are eligible for and - planning to undergo CCRT or SCRT treatment.

4. Patients who had recurred from Stage I/II/III after complete surgery or had gross incomplete resections can be included if they didn't receive treatment with any chemotherapy, radiation therapy, immunotherapy, targeted therapy, or investigational agents.

5. Availability of the EGFRm test results confirming that the tumour harbours one of the two common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R), either alone or in combination with other EGFR mutations including de novo T790M

6. WHO performance status of 0 or 1 with no deterioration over the previous 2 weeks prior to baseline at screening and prior to first dose.

7. Minimum life expectancy of > 12 weeks at Day 1.

8. At least one lesion that can be accurately measured at baseline as = 10 mm in the longest diameter (except lymph nodes, which must have short axis = 15 mm) with CT or MRI and is suitable for accurate repeated measurements.

9. Adequate organ and bone marrow function

10. Male and/or female. Contraceptive use by males or females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies

11. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this CSP.

12. Provision of signed and dated written Optional Genomics Initiative Research Information and Consent Form prior to collection of samples for optional genomics initiative research that supports the Genomic Initiative

Exclusion Criteria:

1. Any presence of small cell and mixed small-cell and non-small cell histology.

2. Past medical history of ILD/pneumonitis, drug-induced ILD, radiation pneumonitis that required steroid treatment, or any evidence of clinically active ILD/pneumonitis.

3. Any unresolved toxicities from prior therapy greater than CTCAE Grade 1 at the time of starting study treatment with the exception of alopecia. Patients with irreversible toxicity that is not reasonably expected to be exacerbated by study intervention in the opinion of the investigator may be included after consultation with the AstraZeneca medical monitor (eg, hearing loss).

4. 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 (eg, patients receiving treatment for infection, including HCV, HIV, and tuberculosis) or active uncontrolled HBV infection.

5. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of osimertinib.

6. History of another primary malignancy except for malignancy treated with curative intent with no known active disease = 2 years before the first dose of study intervention and of low potential risk for recurrence. Exceptions include adequately resected non-melanoma skin cancer and curatively treated in situ disease. Patients who have received RT with overlapping fields (eg, cured breast cancer) should be excluded.

7. Patient meets any of the following cardiac criteria:

1. Mean resting QTc > 470 msec, obtained from 3 ECGs, using the screening clinic ECG machine-derived QTc value.

2. Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG eg, complete left bundle branch block, third degree heart block and second-degree heart block. Patients with atrial fibrillation controlled by medication or arrhythmias controlled by pacemakers may be permitted based on the investigator judgement with cardiologist consultation recommended.

3. History of QT prolongation associated with other medications that required discontinuation of that medication.

8. Congenital long QT syndrome, family history of long QT syndrome, unexplained sudden death under 40 years of age in first-degree relatives or patients with any factors that increase the risk of QTc prolongation/arrhythmic events such as electrolyte abnormalities, heart failure or any concomitant medication known to prolong the QT interval and cause TdP.

9. Patients currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be strong inducers of CYP3A4 (at least 3-week prior to dosing). All patients must try to avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer effects on CYP3A4.

10. Prior treatment with any chemotherapy, radiation therapy, immunotherapy or investigational agents for locally advanced, unresectable Stage III NSCLC. Prior surgical resection (ie, Stage I, II, or III) with no systemic treatment with residual disease or a recurrence is permitted.

11. Prior exposure to EGFR-TKI therapy

12. Major surgical procedure (excluding placement of vascular access) or significant traumatic injury within 4 weeks of the first dose of study intervention or an anticipated need for major surgery during the study.

13. Participation in another clinical study with a study intervention or investigational medicinal device administered in the last 4 weeks (unless the safety profile is known prior to first dose of study intervention), or concurrent enrolment in another clinical study (unless the study is observational [noninterventional], or the patient is in the followup period of an interventional study).

14. History of hypersensitivity to active or inactive excipients of osimertinib or drugs with a similar chemical structure or class to osimertinib.

15. History of hypersensitivity to active or inactive excipients of the chemotherapy regimen of choice (pemetrexed or paclitaxel; cisplatin or carboplatin) or RT or drugs with a similar chemical structure or class to the chemotherapy.

16. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).

17. Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements.

18. Previous enrolment in the present study. Rescreening of individuals who were screen failures is allowed.

19. For females only: Currently pregnant (confirmed with positive pregnancy test) or breastfeeding.

20. Patients should refrain from breastfeeding from enrolment throughout the study and until 6 weeks after last dose of study intervention.

21. In addition, the following are considered criteria for exclusion from the exploratory genetic research:

• Prior allogeneic bone marrow transplant.

• Non-leukocyte depleted whole blood transfusion within 120 days of genetic sample collection.

Related Conditions & MeSH terms

• Lung Cancer
• Lung Neoplasms

Intervention

Drug:
• Osimertinib
80 mg daily (or 40 mg daily for dose reduction)
• Cisplatin or Carboplatin; Pemetrexed or Paclitaxel
Pemetrexed (500 mg/m2 to be administered on Day 1 of every 3-week cycle for 2 cycles) or Paclitaxel (175 mg/m2 on Day 1 of every 3-week cycle for 2 cycles) PLUS Cisplatin (75 mg/m2) or Carboplatin (AUC5) to be administered on Day 1 of every 3--week cycle for 2 cycles
• Radiation
Patients must have received a total dose of radiation of 60 Gy ± 10% (54 to 66 Gy) as part of the chemoradiation therapy. It is recommended but not required that patients have a: Mean lung dose < 20 Gy and/or V20 < 35% Mean oesophagus dose < 34 Gy Heart V50 < 25%, V30 < 50%, and V45 < 35%

Locations

Country	Name	City	State
China	Research Site	Beijing Shi
China	Research Site	Changsha
China	Research Site	Guangzhou
China	Research Site	Hangzhou
China	Research Site	Harbin
China	Research Site	Hefei
China	Research Site	Jinan
China	Research Site	Nanning
China	Research Site	Shanghai
China	Research Site	Shaoguan Shi
China	Research Site	Tianjin Shi
China	Research Site	Wuhan
China	Research Site	Wuhan
China	Research Site	Xi'an
China	Research Site	Zhengzhou
India	Research Site	Gurgaon
India	Research Site	Mohali
India	Research Site	Mumbai
India	Research Site	New Delhi
India	Research Site	Pune
Israel	Research Site	Haifa
Israel	Research Site	Jerusalem
Israel	Research Site	Petach-Tikva
Israel	Research Site	Tel Aviv
Korea, Republic of	Research Site	Cheongju-si
Korea, Republic of	Research Site	Seongnam-si
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Suwon
Spain	Research Site	Badalona
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Donostia-San Sebastian
Spain	Research Site	Granada
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Valencia
Taiwan	Research Site	Hsinchu
Taiwan	Research Site	Taichung
Taiwan	Research Site	Tainan
Taiwan	Research Site	Tainan City
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei City
Thailand	Research Site	Bangkok
Thailand	Research Site	Bangkok
Thailand	Research Site	Chiang Rai
Thailand	Research Site	Hat Yai
Thailand	Research Site	Khlong Toey
Thailand	Research Site	Khon Kaen
Thailand	Research Site	Lampang
Thailand	Research Site	Naimuang
Thailand	Research Site	Rachathewi
Turkey	Research Site	Ankara
Turkey	Research Site	Ankara
Turkey	Research Site	Edirne
Turkey	Research Site	Istanbul
Turkey	Research Site	Istanbul
Turkey	Research Site	Izmir
Turkey	Research Site	Yenimahalle
Turkey	Research Site	Yenimahalle
United States	Research Site	Brooklyn	New York
United States	Research Site	La Jolla	California
United States	Research Site	Los Angeles	California
United States	Research Site	Palo Alto	California
United States	Research Site	Pittsburgh	Pennsylvania
Vietnam	Research Site	Hanoi
Vietnam	Research Site	Hanoi
Vietnam	Research Site	Ho Chi Minh

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Vietnam,  China,  India,  Israel,  Korea, Republic of,  Spain,  Taiwan,  Thailand,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	AEs	To assess the safety of osimertinib used as an induction therapy prior to CRT and maintenance osimertinib treatment by assessment of AEs in patients with unresectable EGFRm NSCLC	from signing ICF to 28 days after last dose or end of study (up to a maximum of approximately 4 years)
Primary	PFS (Progression-Free Survival)	PFS is defined as the time from date of first dose until progression per RECIST 1.1 as assessed by the investigator at the local site, or death due to any cause.	Assessed from date of first dose to progression (up to a maximum of approximately 4 years)
Secondary	ORR (Objective Response Rate)	ORR is defined as the proportion of patients who have a CR or PR, as determined by the investigator at local site per RECIST 1.1.	Assessed during the induction phase of the study, scans are carried out at baseline and week 8 (plus or minus visit window).
Secondary	DCR (Disease Control Rate)	DCR is defined as the percentage of subjects who have a best overall response of CR or PR or SD (at 8 weeks) as determined by the investigator at the local site per RECIST 1.1.	Assessed during the induction phase of the study, scans are carried out at baseline and week 8 (plus or minus visit window).
Secondary	OS (Overall Survival)	OS is defined as time from date of first dose until the date of death due to any cause.	Assessed from first dose to end of study or death (up to a maximum of approximately 4 years)
Secondary	EFS (Event-Free Survival)	EFS is defined as time from date of first dose until any of the following events: progression of disease that precludes CRT or completion of CRT, progression during or after CRT, or death due to any cause.	Assessed from first dose until a progression event or death (up to a maximum of approximately 4 years)