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

NCT ID: NCT04976803

Last Updated: 2022-08-01

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 229 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2021-05-28
• Study Completion Date: 2022-06-30

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.

Detailed Description

The purpose of this study is to address whether ATM genomic aberrations could be used to enrich for patients with ATM LoP. Screening of unselected patient populations for ATM protein loss is likely to a lead to high failure rate by IHC testing, as the prevalence of this is expected to be low. This study could allow for identification of the types of ATM aberrations that lead to ATM LoP, and thus significantly decrease IHC failure rate by pre-selecting patients harboring such aberrations. In this study the investigator will be collecting archival tumor tissue or fresh tissue which will be assessed for ATM LoP and compared to NGS data. Additionally, patients whose tumors exhibit ATM LoP within this study could potentially enroll onto the treatment study REFMAL 721/ART0380C001.

Conditions

Solid Tumor, Unspecified, Adult

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Group A

Deceased patients with archival tissue

Determination of ATM alteration status.

Intervention Type: OTHER

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

Group B

Living patients with archival tissue

Determination of ATM alteration status.

Intervention Type: OTHER

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

Group C

Living patients without archival tissue

Determination of ATM alteration status.

Intervention Type: OTHER

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

Interventions

Determination of ATM alteration status.

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

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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:

1. Previous genetic testing of ATM genomic aberrations.

2. ≥18 years of age.

All living patients (Groups B and C) must also meet the additional criteria:

3. Signed written informed consent to access archival tissue, if available.

All Group C patients must also meet the additional criteria:

4. Provided signed written informed consent to collect a fresh core biopsy.

5. Have a non-irradiated, biopsiable tumor site to allow sampling for analysis via IHC for loss of ATM protein.

6. 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

Exclusion Criteria

Group C patients who meet any of the following criteria will be excluded from study entry:

1. Have a significant bleeding disorder or vasculitis or had a Grade 3 bleeding episode within 12 weeks prior to enrollment.

2. 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:

1. One or more opportunistic HIV/AIDs-related infections within the past 12 months.

2. Documented active or chronic infection with hepatitis B virus (positive hepatitis B surface antigen [+HBsAg]), or hepatitis C virus.

3. Known history of clinical diagnosis of tuberculosis.

4. 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:

1. Have the presence of cardiac disease.

2. Have valvulopathy that is severe, moderate, or deemed clinically significant.

3. Have documented major electrocardiogram (ECG) abnormalities which are clinically significant.

• Have symptomatic or uncontrolled brain metastases, spinal cord compression, or leptomeningeal disease requiring concurrent treatment, including but not limited to surgery, radiation, and/or corticosteroids (patients receiving anticonvulsants are eligible).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Artios Pharma Ltd

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Melissa Johnson, MD

Role: STUDY_CHAIR

Sarah Cannon

Locations

Oklahoma University

Oklahoma City, Oklahoma, United States

Tennessee Oncology

Nashville, Tennessee, United States

Sarah Cannon Research UK

London, , United Kingdom

Countries

United States; United Kingdom

Other Identifiers

ART0380C002

Identifier Type: -

Identifier Source: org_study_id