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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)

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ClinicalTrials.gov Identifier: NCT04765059
Recruitment Status : Not yet recruiting
First Posted : February 21, 2021
Last Update Posted : August 30, 2021
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 who have 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), metastatic NSCLC who responded to first-line osimertinib therapy and subsequently experienced radiological, extracranial disease progression. Approximately 204 patients will 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). 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 : 204 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 the study drug 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)
Estimated Study Start Date : September 30, 2021
Estimated Primary Completion Date : July 15, 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 (intracranial or extracranial, whichever occurs first) per RECIST 1.1 (for extracranial progression) and CNS RECIST 1.1 (for intracranial progression) [ 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 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 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 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 extracranial PFS

  3. OS: the length of time from randomization until the date of 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 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 metastatic EGFRm NSCLC who have progressed extracranially on first line osimertinib treatment



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (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 response with first-line osimertinib treatment but who have not received further, subsequent treatment.
  5. World Health Organization performance status of 0 to 1 at screening with no clinically significant deterioration in the previous 2 weeks.
  6. Life expectancy >12 weeks at Day 1.
  7. At least 1 lesion, not previously irradiated.
  8. Females must be using highly effective contraceptive measures, and must have a negative pregnancy test prior to start of dosing if of child-bearing potential, or must have evidence of non-child-bearing potential by fulfilling criteria at screening.
  9. 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 ILD (interstitial lung disease)/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 extracranial 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 extracranial 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.

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
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United States, Maryland
Research Site
Silver Spring, Maryland, United States, 20910
United States, Massachusetts
Research Site
Boston, Massachusetts, United States, 02114
Research Site
Boston, Massachusetts, United States, 02215
United States, Minnesota
Research Site
Minneapolis, Minnesota, United States, 55407
Austria
Research Site
Graz, Austria, 8036
Research Site
Klagenfurt, Austria, 9020
Research Site
Linz, Austria, 4020
China
Research Site
Beijing, China, 100005
Research Site
Beijing, China, 100142
Research Site
Hohhot, China, 010017
Research Site
Shenyang, China, 110001
Research Site
Tianjin, China, 300060
Research Site
Zhengzhou City, China, 450008
Germany
Research Site
Berlin, Germany, 12351
Research Site
Hannover, Germany, 30625
Research Site
Hessen, Germany, 61231
Research Site
Karlsruhe, Germany, 76137
Research Site
Köln, Germany, 50937
Research Site
Köln, Germany, 51109
Research Site
München, Germany, D-80336
Research Site
Ulm, Germany, 89081
Israel
Research Site
Beer Sheva, Israel, 84101
Research Site
Jerusalem, Israel, 9103102
Research Site
Jerusalem, Israel, 9112001
Research Site
Kfar Saba, Israel, 4428164
Research Site
Petah Tikva, Israel, 494142
Research Site
Tel Aviv, Israel, 6423906
Research Site
Tel Hashomer, Israel, 52621
Italy
Research Site
Firenze, Italy, 50134
Research Site
Meldola, Italy, 47014
Research Site
Messina, Italy, 98158
Research Site
Napoli, Italy, 80131
Research Site
Padova, Italy, 35128
Research Site
Palermo, Italy, 90146
Research Site
Roma, Italy, 00168
Research Site
Terni, Italy, 05100
Research Site
Verona, Italy, 37124
Spain
Research Site
Alicante, Spain, 03010
Research Site
León, Spain, 24071
Research Site
Madrid, Spain, 28040
Research Site
Oviedo, Spain, 33011
Research Site
Palma de Mallorca, Spain, 07010
Research Site
Sevilla, Spain, 41013
Research Site
Valencia, Spain, 46010
Sponsors and Collaborators
AstraZeneca
Parexel
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT04765059    
Other Study ID Numbers: D5162C00042
First Posted: February 21, 2021    Key Record Dates
Last Update Posted: August 30, 2021
Last Verified: August 2021
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. 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 shared.

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 Pharma 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 de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at:

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

URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

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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
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Bronchial Neoplasms
Carcinoma, Non-Small-Cell Lung
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Cisplatin
Carboplatin
Pemetrexed
Osimertinib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors
Protein Kinase Inhibitors