Tissue Collection for Correlation Between ATM Alterations by Next-Generation Sequencing and ATM Loss-of-Protein

NCT04976803 | Completed

• 1 other identifier: ART0380C002
• Study Type: observational
• Target: 229
• Locations: 2 countries
• Sites: 3

Brief Summary

This study examines the correlation between ATM alterations identified using NGS profiles with ATM protein expression levels from tumor tissue assessed by IHC.

Conditions

Solid Tumor, Unspecified, Adult

Keywords

ATM; DDR; ATR; protein expression; LoF

Outcome Measures

Primary Outcomes (1)

• Number of patients with loss of ATM protein

  ATM protein expression levels from tumor tissue assessed by immunohistochemistry (IHC)

  12 months

Secondary Outcomes (3)

• Number of potential patients with loss of ATM protein eligible for study REFMAL 721/ART0380C001

  12 months

• Number of ATM genomic aberrations that lead to ATM LoP

  12 months

• Rate of loss of function (LoF) of the ATM gene in patients with genomic aberrations in the ATM gene

  12 months

Study Arms (3)

Group A

Deceased patients with archival tissue

Other: Determination of ATM alteration status.

Group B

Living patients with archival tissue

Other: Determination of ATM alteration status.

Group C

Living patients without archival tissue

Other: Determination of ATM alteration status.

Interventions

Determination of ATM alteration status. OTHER

ATM alterations identified using NGS profiles with ATM protein expression levels from tumor tissue assessed by IHC.

Group A; Group B; Group C

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with identified ATM alterations will be potentially enrolled into this study in 1 of 3 patient populations * Group A: Deceased patients with archival tumor tissue * Group B: Living patients with archival tumor tissue * Group C: Living patients without archival tumor tissue

You may qualify if:

• Patients must meet the following criteria in order to be included in the research study:
• All patients (Groups A, B, and C) must meet the following criteria:
• Previous genetic testing of ATM genomic aberrations.
• ≥18 years of age.
• All living patients (Groups B and C) must also meet the additional criteria:
• Signed written informed consent to access archival tissue, if available.
• All Group C patients must also meet the additional criteria:
• Provided signed written informed consent to collect a fresh core biopsy.
• Have a non-irradiated, biopsiable tumor site to allow sampling for analysis via IHC for loss of ATM protein.
• Potentially eligible for REFMAL 721/ART0380C001:
• Have not received a previous treatment targeting the ATR/CHK1 pathway.
• If patients have a germline BRCA mutation or a cancer with a somatic BRCA mutation or which is HRD positive and for which there is an approved PARP inhibitor, patients should have received such treatment.
• Have an estimated life expectancy of ≥12 weeks, in the judgment of the investigator
• Advanced or metastatic cancer which is refractory to standard therapies, or for which no standard therapies exist, or for which the investigator feels no other active therapy is required for the duration of the study.
• Performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG) scale

You may not qualify if:

• Group C patients who meet any of the following criteria will be excluded from study entry:
• Have a significant bleeding disorder or vasculitis or had a Grade 3 bleeding episode within 12 weeks prior to enrollment.
• Presumed ineligible for enrollment to REFMAL 721/ART0380C001:
• Psychological, familial, sociological, or geographical conditions that that would compromise the patient's ability to adhere to future procedures likely in a Phase I protocol (such as REFMAL 721/ ART0380C001).
• Women who are pregnant, breast feeding, or who plan to become pregnant within the next 6 months.
• Men who plan to father a child within the next 6 months.
• Have a serious concomitant systemic disorder that would compromise the patient's ability to adhere to a future protocol (REFMAL 721/ ART0380C001) including:
• One or more opportunistic HIV/AIDs-related infections within the past 12 months.
• Documented active or chronic infection with hepatitis B virus (positive hepatitis B surface antigen \[+HBsAg\]), or hepatitis C virus.
• Known history of clinical diagnosis of tuberculosis.
• Have had a malignancy prior to the current malignancy. Patients with carcinoma in situ of any origin and patients with prior malignancies who are in remission and whose likelihood of recurrence is very low (such as basal cell carcinoma), as judged by the medical monitor, are eligible for this study.
• Have evidence of interstitial lung disease or pneumonitis (whether symptomatic or asymptomatic).
• Have moderate or severe cardiovascular disease, such as the following:
• Have the presence of cardiac disease.
• Have valvulopathy that is severe, moderate, or deemed clinically significant.

Sponsors & Collaborators

• Artios Pharma Ltd: lead

Study Sites (3)

Oklahoma University

Oklahoma City, Oklahoma, 37104, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

Sarah Cannon Research UK

London, W1G6AD, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITH DNA

A formalin-fixed tumor tissue block or 5 freshly cut air-dried sections mounted on positively charged slides. Tissue sections cut from the blocks should be 4-5 micron thickness.

Study Officials

• Melissa Johnson, MD

  Sarah Cannon

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 5, 2021
• First Posted: July 26, 2021
• Study Start: May 28, 2021
• Primary Completion: June 30, 2022
• Study Completion: June 30, 2022
• Last Updated: August 1, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (2); GB (1)