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PDX Models From EGFR Mutant Tumors

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ClinicalTrials.gov Identifier: NCT03872440
Recruitment Status : Recruiting
First Posted : March 13, 2019
Last Update Posted : March 13, 2019
Sponsor:
Information provided by (Responsible Party):
Addario Lung Cancer Medical Institute

Brief Summary:
A biospecimen collection study from individuals with EGFR mutant cancers resistant to EGFR TKIs or those harboring an Exon 20 insertion mutation.

Condition or disease
Non Small Cell Lung Cancer

Detailed Description:

EGFR mutations are detected in approximately 15% of all patients diagnosed with lung cancer. There are several types of EGFR mutations including both the common L858R and exon 19 deletions (accounting for 85%) or the rare exon 20 insertion (accounting for 5-8%) EGFR mutations.

Different types of therapies are being used for these two groups of EGFR mutations. Osimertinib is an EGFR inhibitor approved for patients newly diagnosed with EGFR exon 19 or L858R mutations and for patients who have been treated with a prior EGFR inhibitor but have developed EGFR T790M as a resistance mechanism. In contrast, there are no approved EGFR inhibitors for patients with EGFR or HER2 exon 20 insertion mutations although several therapies are under evaluation in clinical trials.

The Addario Lung Cancer Medical Institute (ALCMI) would like to focus on studying the cancers of patients previously treated with osimertinib or those with EGFR or HER2 exon 20 insertion mutations. The goal is to better understand how these tumors respond to drugs, and what happens when tumors stop responding to drugs. By studying these cancers ALCMI hopes to accelerate the development of new therapeutic approaches for patients with EGFR mutant lung cancer.


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Study Type : Observational
Estimated Enrollment : 50 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: ALCMI-012 A Prospective Biospecimen Collection Study From Patients With EGFR Mutant Tumors
Actual Study Start Date : November 14, 2018
Estimated Primary Completion Date : November 2022
Estimated Study Completion Date : November 2022

Resource links provided by the National Library of Medicine


Group/Cohort
EGFR T790M patients
EGFR T790M patients who have progressed on osimertinib or other third generation (mutant selective) EGFR TKI therapy
EGFR exon 19 del or L858R patients
EGFR exon 19 del or L858R patients who have progressed on first line osimertinib
Exon 20 insertion mutations patients
Patients with Exon 20 insertion mutations (n=10; regardless of drug therapy). Includes EGFR Exon 20 and up to two HER2 Exon20 patients



Primary Outcome Measures :
  1. The primary objective is to develop a unique cohort of PDX models from EGFR mutant cancers as a resource to the research community. [ Time Frame: 48 months ]
    Successful generation of at least fifty (50) PDX models with full characterization including whole exome sequencing (WES) and RNA sequencing. These PDX models will be used to inform the study of EGFR-driven cancers at large.


Biospecimen Retention:   Samples With DNA

The purpose of this study is the successful generation of at least ten (10), EGFR mutant PDX models with full characterization including whole exome sequencing (WES) and RNA sequencing. The models will be generated from three major cohorts:

A.) EGFR T790M patients who have progressed on osimertinib or other third generation (mutant selective) EGFR TKI therapy (n=20) and

B.) EGFR exon 19 del or L858R patients who have progressed on first line osimertinib (n=20) and

C.) patients with Exon 20 insertion mutations (n=10; regardless of drug therapy). Includes EGFR Exon 20 and up to two HER2 Exon20 patients.

The estimates take into consideration an overall take rate of 20%. Models can be used as a resource for clinical and translational research to understand mechanisms of resistance and develop new therapies. For cohort B there is no requirement for a specific number of patients with either EGFR exon 19 deletion or L858R mutations.



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 and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
A total of fifty (50) implantations from approximately fifty (50) subjects, meeting all of the inclusion and none of the exclusion criteria to establish a minimum of ten (10) PDX models.
Criteria

Inclusion Criteria:

  • a. Male or female greater than 18 years of age at the time of consent or the age of majority in their residing state.

    b. Confirmed diagnosis of EGFR mutant NSCLC.

    1. EGFR T790M patients who have progressed on osimertinib or other third generation (mutant selective) EGFR TKI therapy or
    2. Patients must have an EGFR exon 19 deletion or L858R and progressed on first line osimertinib or
    3. Patients with an exon EGFR or HER2 20 insertion mutation.

    c. A clinically-indicated procedure (required by the patient's treating physician) scheduled no more than 30 calendar days from date of consent.

    d. A minimum of 21 calendar days between the last dose of systemic therapy and the clinically-indicated procedure is strongly requested but not required*.

    e. A minimum of 48 hours between the last dose of an osimertinib therapy or other targeted therapies and the time of the clinically-indicated procedure is strongly requested but not required*.

    f. Willingness to undergo all study collection procedures and follow up. g. Provision of written informed consent by the patient. h. Able to communicate (read, write and speak) in English. i. Clinically-indicated procedure to be performed within the US (including Alaska, Hawaii and Puerto Rico), Canada, England, or Israel.

    *A treatment washout period is considered best practice for building a PDX from a tumor specimen. However, if this is not medically possible, material may still be accepted to attempt to build a PDX. This may have a significant impact on take rate therefore accepting tumor specimens with no washout period can impact the overall expected take rate of the program.

Exclusion Criteria:

  • a. Less than 18 years of age or age of majority for their residing state, at time of consent.

    b. No confirmed diagnosis of EGFR exon 19 deletion, L858R or EGFR or HER2 exon 20 mutation. Patients whose tumors harbor EGFR mutations other than an exon 19 deletion, L858R or exon 20 EGFR insertion or HER2 exon 20 insertions are not eligible.

    c. A biopsy or surgical procedure not scheduled for clinical/diagnostic purposes.

    d. Pleural effusion specimens collected outside of the US. e. A clinically-indicated procedure scheduled more than 30 calendar days from the date of consent.

    f. Unwilling to undergo all study collection procedures and follow up. g. Unable or unwilling to provide consent. h. Unable to communicate in English. j. Clinically-indicated procedure not scheduled within the US, Canada, England, or Israel.


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): NCT03872440


Contacts
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Contact: Alicia Sable-Hunt, RN, MBA, CCRA 888-403-3437 asable-hunt@alcmi.net
Contact: Richard Erwin 248-444-2181 rerwin@alcmi.net

Locations
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United States, California
Addario Lung Cancer Medical Institute Recruiting
San Carlos, California, United States, 94070
Contact: Alicia L Sable-Hunt, RN    888-403-3437    clinicalops@alcmi.net   
Principal Investigator: Pasi A Janne, MD, PhD         
Sponsors and Collaborators
Addario Lung Cancer Medical Institute

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Responsible Party: Addario Lung Cancer Medical Institute
ClinicalTrials.gov Identifier: NCT03872440     History of Changes
Other Study ID Numbers: ALCMI-012
First Posted: March 13, 2019    Key Record Dates
Last Update Posted: March 13, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Addario Lung Cancer Medical Institute:
EGFR mutant cancer
Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases