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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04765059
Recruitment Status : Recruiting
First Posted : February 21, 2021
Last Update Posted : January 22, 2024
Sponsor:
Collaborator:
Parexel
Information provided by (Responsible Party):
AstraZeneca

Brief 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.

Condition or disease Intervention/treatment Phase
Non-small Cell Lung Cancer Drug: Osimertinib (AZD9291) pemetrexed cisplatin or carboplatin Drug: Placebo for osimertinib (AZD9291) pemetrexed cisplatin or carboplatin Phase 3

Detailed 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: The patient, the Investigator, and the study site staff will be blinded to osimertinib or placebo allocation. Patients may participate in the open label part of trial at the discretion of the investigator to receive osimertinib and continue any ongoing chemotherapy if intracranial progression is their first progression event.
Primary Purpose: Treatment
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)
Actual Study Start Date : September 12, 2021
Estimated Primary Completion Date : December 30, 2024
Estimated Study Completion Date : December 30, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Treatment Arm A
All randomized patients will receive osimertinib 80 mg QD with pemetrexed (500 mg/m^2) (with pre-treatment) plus either cisplatin (75 mg/m^2) or carboplatin ([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
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 Comparator: Treatment Arm B
All randomized patients will receive 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
Drug: 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




Primary Outcome Measures :
  1. 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 [ Time Frame: 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) ]
    To compare the efficacy of chemotherapy plus osimertinib treatment relative to chemotherapy plus placebo based on PFS


Secondary Outcome Measures :
  1. 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 [ Time Frame: 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) ]
    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

  2. 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 [ Time Frame: 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) ]
    To compare the efficacy of chemotherapy plus osimertinib treatment relative to chemotherapy plus placebo based on extracranial PFS

  3. OS: the length of time from randomization until the date of death due to any cause [ Time Frame: From randomization through post progression survival follow-up (up to approximately 3 years) ]
    To compare the efficacy of chemotherapy plus osimertinib treatment relative to chemotherapy plus placebo based on OS

  4. Number of patients with serious and non-serious adverse events [ Time Frame: From screening through post progression survival follow-up (at least once every 12 weeks relative to randomization) ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 130 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04765059


Contacts
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Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

Locations
Show Show 57 study locations
Sponsors and Collaborators
AstraZeneca
Parexel
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT04765059    
Other Study ID Numbers: D5162C00042
2019-003969-18 ( EudraCT Number )
First Posted: February 21, 2021    Key Record Dates
Last Update Posted: January 22, 2024
Last Verified: January 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

"Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.

Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame:

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
URL: https://vivli.org/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AstraZeneca:
Osimertinib
Platinum
Pemetrexed
Epidermal growth factor receptor mutation positive (EGFRm)
Extracranial progression
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Cisplatin
Carboplatin
Pemetrexed
Osimertinib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors
Protein Kinase Inhibitors