A Study to Evaluate Chemotherapy Plus Osimertinib Against Chemotherapy Plus Placebo in Patients With Non-small Cell Lung Cancer (NSCLC)

Non-small Cell Lung Cancer Clinical Trial

— COMPEL  

Official title:

A Phase III, Randomized, Double-Blind, Placebo-Controlled Study of Platinum Plus Pemetrexed Chemotherapy Plus Osimertinib Versus Platinum Plus Pemetrexed Chemotherapy Plus Placebo in Patients With EGFRm, Locally Advanced or Metastatic NSCLC Who Have Progressed Extracranially Following First-Line Osimertinib Therapy (COMPEL)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04765059
• Other study ID #: D5162C00042
• Secondary ID: 2019-003969-18
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: September 12, 2021
• Est. completion date: December 30, 2024

Study information

• Verified date: February 2024
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study will evaluate the efficacy and safety of treatment with chemotherapy in combination with osimertinib compared to chemotherapy in combination with placebo in patients whose disease has progressed extracranially following first-line osimertinib treatment.

Description:

This is a Phase III, randomized, double-blind, placebo-controlled study of platinum plus pemetrexed chemotherapy plus osimertinib versus platinum plus pemetrexed chemotherapy plus placebo in patients with epidermal growth factor receptor mutation-positive (EGFRm), locally advanced or metastatic NSCLC with or wihout stable brain metastases who responded to first-line osimertinib therapy (complete response [CR] or partial response [PR]) or stable disease (SD) for ≥ 6 months during first-line osimertinib treatment, and subsequently experienced radiological, extracranial disease progression. Approximately 204 patients were to be randomized in a 1:1 ratio to treatment with platinum plus pemetrexed chemotherapy plus osimertinib (Treatment Arm A) or platinum plus pemetrexed chemotherapy plus placebo (Treatment Arm B). However, the number of patients has been reduced to approximately 80 patients due to treatment landscape changes which outpaced study recruitment. Patients will be stratified based on the presence of brain metastases (stable brain metastases based on central nervous system (CNS) Response Evaluation Criteria in Solid Tumors, Version 1.1 [RECIST 1.1] assessments versus no brain metastases). The 2 randomized treatment regimens are as follows: - Treatment Arm A: Osimertinib 80 mg once daily (QD) with pemetrexed (500 mg/m^2) (with pre-treatment) plus either cisplatin (75 mg/m^2) or carboplatin (area under the concentration-time curve [AUC] 5), both administered on Day 1 of 21-day cycles for 4 cycles, followed by osimertinib 80 mg QD plus pemetrexed maintenance (500 mg/m^2) on Day 1 of 21-day cycles - Treatment Arm B: Placebo QD with pemetrexed (500 mg/m^2) (with pre-treatment) plus either cisplatin (75 mg/m^2) or carboplatin (AUC5), both administered on Day 1 of 21-day cycles for 4 cycles, followed by placebo QD plus pemetrexed maintenance (500 mg/m^2) on Day 1 of 21-day cycles.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 97
• Est. completion date: December 30, 2024
• Est. primary completion date: December 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 130 Years

Eligibility

Inclusion Criteria:

1. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form and in this protocol.

2. Pathologically confirmed non-squamous NSCLC.

3. Locally advanced (clinical stage IIIB or IIIC) or metastatic NSCLC (clinical stage IVA or IVB) or recurrent NSCLC, not amenable to curative surgery or radiotherapy.

4. Evidence of radiological extracranial disease progression following (Investigator-assessed) response or SD for = 6 months during first-line osimertinib treatment, but who have not received further, subsequent treatment.

5. Tumor known to harbor 1 of the 2 or both common epidermal growth factor receptor (EGFR) mutations known to be associated with EGFR tyrosine kinase inhibitor (TKI) sensitivity (Ex19del or L858R), either alone or in combination with other EGFR mutations, which may include T790M.

6. World Health Organization performance status of 0 to 1 at screening with no clinically significant deterioration in the previous 2 weeks.

7. Life expectancy >12 weeks at Day 1.

8. At least 1 lesion, not previously irradiated, that can be accurately measured.

9. Females must be using highly effective contraceptive measures, and must have a negative pregnancy test prior to start of dosing if of childbearing potential, or must have evidence of non-childbearing potential by fulfilling criteria at screening.

10. Male patients must be willing to use barrier contraception

Exclusion Criteria:

1. Clinical or radiological evidence of CNS progression on first-line osimertinib.

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

3. Any evidence of severe or uncontrolled systemic diseases.

4. Any of the following cardiac criteria:

i) Mean resting QTc >470 msec ii) Any clinically important abnormalities in rhythm, conduction, or morphology of resting electrocardiogram iii) Any factors that increase the risk of QTc prolongation or risk of arrhythmic events

5. Any concurrent and/or other active malignancy that has required treatment within 2 years of first dose of investigational product (IP).

6. Any unresolved toxicities from prior therapy.

7. 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.

8. More than 4 weeks elapsed since last dose of osimertinib by date of randomization.

9. Unable to tolerate osimertinib 80 mg first-line therapy.

10. Prior treatment with any systemic anti-cancer therapy.

11. Major surgery within 4 weeks of the first dose of IP.

12. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of IP.

13. Current use of medications or herbal supplements known to be strong inducers of cytochrome P450 (CYP) 3A4.

14. Participation in another clinical study with an IP other than first-line osimertinib during the 4 weeks prior to Day 1.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer

Intervention

Drug:
• Osimertinib (AZD9291) pemetrexed cisplatin or carboplatin
Randomized patients will receive oral dose of osimertinib with intravenous (IV) pemetrexed plus either IV cisplatin or IV carboplatin
• Placebo for osimertinib (AZD9291) pemetrexed cisplatin or carboplatin
Randomized patients will receive oral dose of placebo matching osimertinib with IV pemetrexed plus either IV cisplatin or IV carboplatin

Locations

Country	Name	City	State
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Ganzhou
China	Research Site	Guangzhou
China	Research Site	Hohhot
China	Research Site	Jinan
China	Research Site	Linyi
China	Research Site	Shenyang
China	Research Site	Tianjin
China	Research Site	Wuxi
China	Research Site	Xiangfan
China	Research Site	Zhengzhou City
Germany	Research Site	Berlin
Germany	Research Site	Hannover
Germany	Research Site	Köln
Germany	Research Site	Köln
Germany	Research Site	München
Germany	Research Site	Ulm
Israel	Research Site	Beer Sheva
Israel	Research Site	Jerusalem
Israel	Research Site	Jerusalem
Israel	Research Site	Kfar Saba
Israel	Research Site	Tel Aviv
Israel	Research Site	Tel Hashomer
Italy	Research Site	Firenze
Italy	Research Site	Meldola
Italy	Research Site	Messina
Italy	Research Site	Napoli
Italy	Research Site	Padova
Italy	Research Site	Roma
Italy	Research Site	Terni
Italy	Research Site	Verona
Spain	Research Site	Alicante
Spain	Research Site	Barcelona
Spain	Research Site	Cáceres
Spain	Research Site	Cordoba
Spain	Research Site	León
Spain	Research Site	Madrid
Spain	Research Site	Málaga
Spain	Research Site	Murcia
Spain	Research Site	Oviedo
Spain	Research Site	Palma de Mallorca
Spain	Research Site	Sevilla
Spain	Research Site	Valencia
United States	Research Site	Boston	Massachusetts
United States	Research Site	Minneapolis	Minnesota
United States	Research Site	Silver Spring	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Parexel

Countries where clinical trial is conducted

United States,  China,  Germany,  Israel,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression free survival(PFS):time from randomization until progression(intra- or extracranial whichever occurs first)per RECIST 1.1(for extracranial)and CNS RECIST 1.1(for intracranial progression)as assessed by Investigator or death due to any cause	To compare the efficacy of chemotherapy plus osimertinib treatment relative to chemotherapy plus placebo based on PFS	At Screening,every 6 weeks for the first 13 cycles (each cycle is 21 days),then every 12 weeks, relative to randomization,and upto intracranial or extracranial disease progression or end of survival follow-up,whichever comes first (approximately 3 years)
Secondary	Intracranial PFS is defined as time from randomization until intracranial progression per CNS RECIST 1.1 as assessed by the Investigator at local site or death due to any cause	To compare the efficacy of chemotherapy plus osimertinib treatment relative to chemotherapy plus placebo based on intracranial PFS in patients with baseline brain metastases and patients without baseline brain metastases	At Screening,every 6 weeks for the first 13 cycles (each cycle is 21 days), then every 12 weeks, relative to randomization, and upto intracranial disease progression or end of survival follow-up, whichever comes first (approximately 3 years)
Secondary	Extracranial PFS is defined as time from randomization until extracranial progression per RECIST 1.1 as assessed by the Investigator at local site or death due to any cause	To compare the efficacy of chemotherapy plus osimertinib treatment relative to chemotherapy plus placebo based on extracranial PFS	At Screening,every 6 weeks for the first 13 cycles (each cycle is 21 days), then every 12 weeks, relative to randomization, and upto extracranial disease progression or end of survival follow-up, whichever comes first (approximately 3 years)
Secondary	OS: the length of time from randomization until the date of death due to any cause	To compare the efficacy of chemotherapy plus osimertinib treatment relative to chemotherapy plus placebo based on OS	From randomization through post progression survival follow-up (up to approximately 3 years)
Secondary	Number of patients with serious and non-serious adverse events	To assess the safety and tolerability of chemotherapy plus osimertinib treatment relative to chemotherapy plus placebo in patients with locally advanced or metastatic EGFRm NSCLC whose disease has progressed extracranially on first-line osimertinib treatment.	From screening through post progression survival follow-up (at least once every 12 weeks relative to randomization)