Genetic Testing for Young Adults with Cancer

(Gen-Y Trial)

Overseen By Katherine Gleason, MPH

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Pennsylvania

Disqualifiers: In situ cancer, Thyroid cancer, Leukemia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method to determine if young adults with cancer have a genetic risk, which is a tendency passed down through family. The trial compares universal genetic testing using a broad 66-gene panel for young adult cancers with standard testing methods to identify which is more effective at detecting genetic risks. It aims to simplify genetic testing decisions and help doctors identify those at risk more easily. Suitable participants have been diagnosed with a solid tumor in the past year and have had at least two visits at Penn Medicine for their cancer diagnosis. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could simplify genetic testing for future patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What prior data suggests that this genetic testing approach is safe?

Research has shown that multigene panel testing, such as the 66-gene panel for young adult cancers, is generally easy for participants to handle. These tests identify genetic changes that might increase cancer risk. Studies have found that this genetic testing poses no physical or health risks to participants.

The broad gene panel for young adult cancers also detects genetic changes. This testing is safe because it involves analyzing DNA from a sample, usually blood or saliva. No negative effects are known from this type of genetic analysis.

Both types of genetic panels identify cancer risks without causing harm or discomfort. Prospective trial participants can feel confident that these tests are safe and non-invasive. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about genetic testing for young adults with cancer because it offers a more comprehensive approach to understanding cancer risk. Unlike the standard method, which typically focuses on genetic testing based on specific guidelines like age and family history, the experimental approach uses a broad panel of cancer risk genes. This could potentially identify genetic risks that are missed by more traditional panels. By providing a more detailed genetic profile, this method could lead to earlier and more personalized interventions, which is why there's so much excitement around it.

What evidence suggests that this trial's treatments could be effective for identifying genetic risk in young adults with cancer?

Research has shown that the 66-gene panel, which participants in this trial may receive, can identify many hereditary cancer risks in young adults. This panel includes genes linked to various types of cancer, helping to uncover risks that might otherwise go unnoticed. Another treatment arm in this trial uses a broad genetic panel, which has effectively identified cancer risk genes by examining DNA from tumors. These panels enable doctors to better understand a person’s genetic risk for cancer. Early findings suggest that these tools can significantly aid in the early detection of cancer risks. ^{1 2 4 6 7}

Who Is on the Research Team?

Steven Joffe, MD

Principal Investigator

University of Pennsylvania

Katherine L Nathanson, MD

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

This trial is for young adults aged 18-39, diagnosed with a solid tumor cancer within the last year and have visited Penn Medicine at least twice. It's not for those who already know they have a genetic predisposition to cancer, have certain types of thyroid or in situ cancers, leukemia, or had previous genetic testing after their diagnosis.

Inclusion Criteria

I was diagnosed with my current cancer less than a year ago.

Have had at least two visits at Penn Medicine for the cancer diagnosis (to exclude one-time second opinions)

You can participate in the study if you meet these requirements:

Exclusion Criteria

I have had genetic testing for my cancer.

You will not be able to participate in the study if you meet any of these conditions:

I have a genetic condition that increases my cancer risk.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Enrollment and Randomization

Consenting patients are randomized into study arms and complete initial surveys

12 months

1 visit (in-person or virtual)

Genetic Testing

Participants undergo genetic testing using a broad cancer risk gene panel

3 months

1 visit (in-person or virtual)

Follow-up

Participants are monitored for adherence to risk reduction interventions and genetic risk ascertainment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• 66-gene panel for young adult cancers
• Broad gene panel for young adult cancers
• Standard

Trial Overview The study tests if using broad gene panels for genetic screening can better identify genetic risks in young adults with cancer compared to standard practices. It uses EMR-based algorithms aiming to simplify the process and potentially involve patients' relatives as well.

How Is the Trial Designed?

Group I: Universal genetic testing Experimental Treatment 1 Intervention

Detection of genetic risk using a broad panel of cancer risk genes.

Group II: Standard Active Control 1 Intervention

We will refer a subset of patients who meet guideline criteria based on age, cancer type, and family history, for genetic counseling and testing.

66-gene panel for young adult cancers is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Hereditary Cancer Gene Panel for:

• Breast cancer
• Ovarian cancer
• Colorectal cancer
• Pancreatic cancer
• Prostate cancer

Approved in European Union as Multigene Panel Test for:

• Breast cancer
• Ovarian cancer
• Colorectal cancer
• Pancreatic cancer
• Prostate cancer
• Other hereditary cancers

Approved in Canada as Genetic Risk Assessment Panel for:

• Breast cancer
• Ovarian cancer
• Colorectal cancer
• Pancreatic cancer

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Published Research Related to This Trial

Multi-gene panel testing for hereditary cancer is becoming more common in clinical practice as sequencing technology improves, allowing for better understanding of the genetic causes of cancer.

The chapter discusses the importance of genetic counseling before and after testing, emphasizing how results from multi-gene panels can guide patient management and treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multigene Panel Testing for Hereditary Cancer and Genetic Counseling. Lee, ES., Kim, J., Han, W.[2021]

In a study of 3,251 patients referred for hereditary breast and ovarian cancer testing, 9.1% received a positive result indicating a pathogenic variant, with BRCA1 and BRCA2 being the most commonly identified genes.

A significant 27.1% of results were inconclusive, highlighting the need for further research and data-sharing to clarify the clinical significance of these variants and improve the utility of multigene panel testing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multigene panel testing for hereditary breast and ovarian cancer in the province of Ontario. Lerner-Ellis, J., Mighton, C., Lazaro, C., et al.[2021]

In a study of 2237 breast cancer patients, large panel genetic testing identified 12.8% with actionable deleterious mutations, which were not detected by abbreviated panels, highlighting the importance of comprehensive testing.

Patients with deleterious mutations had a higher rate of bilateral mastectomy (53.7%) compared to those with negative results (31%) or variants of undetermined significance (32.6%), indicating that identifying these mutations can significantly influence treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of large panel genetic evaluation of breast cancer patients in a community-based cancer institute. Bagwell, AK., Sutton, TL., Gardiner, S., et al.[2021]

Somatic and germline multiple-gene panel tests are becoming essential in cancer diagnosis and treatment, allowing for better identification of hereditary tumor syndromes and selection of targeted therapies.

The introduction of these advanced genetic tests in Japan is changing the traditional approach to cancer treatment, highlighting the need for new systems to interpret genetic information and provide preventive care for patients and their families.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Current Status and Challenges of Clinical Practice for Hereditary Tumor Syndromes]. Imoto, I., Takaiso, N.[2019]

In a study of 252,223 individuals, genetic testing using a 25-gene pan-cancer panel identified pathogenic variants (PVs) in 6.7% of participants, highlighting its effectiveness in detecting inherited cancer risks.

The testing revealed that a significant portion of PVs occurred in genes outside of the commonly tested BRCA1/2 and Lynch syndrome genes, suggesting that pan-cancer panels may offer better clinical utility than traditional single-gene tests.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical testing with a panel of 25 genes associated with increased cancer risk results in a significant increase in clinically significant findings across a broad range of cancer histories. Rosenthal, ET., Bernhisel, R., Brown, K., et al.[2022]

A 24-year-old woman with a BRCA1 pathogenic variant was diagnosed with endometrial carcinoma and underwent extensive surgery, highlighting the importance of genetic testing in understanding her cancer risk.

Multigene panel testing (MGPT) revealed her and her mother's high risk for hereditary breast and ovarian cancer syndrome (HBOC), suggesting that MGPT can enhance cancer risk assessment and management strategies for patients with complex family histories.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detection of BRCA1 Pathogenic Variant in a 24-Year-Old Endometrial Cancer Patient: Risks of Several Hereditary Tumor Syndromes Assessed Using Germline Multigene Panel Testing. Wang, X., Kaneko, K., Arakawa, H., et al.[2022]

In a study of 630 individuals tested with a 27-gene inherited cancer panel, a positive rate of 10.3% for pathogenic or likely pathogenic variants was found, indicating the effectiveness of multi-gene panel testing in identifying inherited cancer predispositions.

More than half of the identified variants were in genes with moderate to low risk, highlighting the importance of testing beyond just classic hereditary cancer syndromes like HBOC and Lynch Syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of a 27-gene inherited cancer panel across 630 consecutive patients referred for testing in a clinical diagnostic laboratory. Gardner, SA., Weymouth, KS., Kelly, WS., et al.[2022]

In a study of 348 multigene panel tests, including genes beyond historically high-risk ones, the positive result rate increased from 6.2% to 17%, highlighting the value of expanded testing in identifying hereditary cancer risks.

However, 42% of results returned variants of uncertain significance (VUS), emphasizing the need for thorough pre-test counseling and the use of phenotype-specific panels to manage the ambiguity of test results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Application of Multigene Panels: Challenges of Next-Generation Counseling and Cancer Risk Management. Slavin, TP., Niell-Swiller, M., Solomon, I., et al.[2022]

Patients with pathogenic variants in breast cancer genes, including BRCA1/2 and other less-studied genes, reported inadequate information and support from healthcare providers, highlighting a gap in education and awareness regarding non-BRCA1/2 variants.

Despite established guidelines for BRCA1/2, patients with these variants also experienced similar issues with healthcare communication, indicating a broader need for improved education for both patients and providers about hereditary cancer genetics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patients with pathogenic variants for breast cancer other than BRCA1 and BRCA2: qualitative interviews about health care experiences. Clift, KE., Macklin, SK., Hines, SL.[2022]

In a study of 415 breast cancer patients undergoing genetic testing, 92% had germline findings that provided actionable information for treatment decisions and risk estimates for breast and other cancers.

The majority of patients (57.1%) had pathogenic variants in high-risk genes, indicating that multi-gene panels can effectively identify individuals at significant risk and guide personalized management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Revisiting the Implications of Positive Germline Testing Results Using Multi-gene Panels in Breast Cancer Patients. Tsaousis, GN., Papadopoulou, E., Agiannitopoulos, K., et al.[2022]

A study involving 246 parents showed that opinions on BRCA1/2 genetic testing for minors are mixed, with 37% supporting it outright and 47% supporting it under certain circumstances.

Factors influencing support for testing included the parent's own negative test result, being male, and belonging to a minority race, indicating that personal experiences and demographics may shape views on genetic testing for children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Parent opinions regarding the genetic testing of minors for BRCA1/2. Bradbury, AR., Patrick-Miller, L., Egleston, B., et al.[2010]

In a study of 143 adolescents and young adults with colorectal cancer (CRC) diagnosed at age 35 or younger, hereditary syndromes were found in 29.4% of patients, highlighting the importance of genetic evaluation in this age group.

While CRC-specific gene panel testing did not significantly increase the diagnostic yield for patients without a suggestive personal or family history, it did identify variants in about one-third of cases, suggesting that broader genetic testing might be more beneficial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of disease-specific next-generation sequencing gene panel testing in adolescents and young adults with colorectal cancer. Mork, ME., Rodriguez, A., Bannon, SA., et al.[2020]

Citations

1. withpower.com withpower.com/trial/phase-11-2020-061a7

Genetic Testing for Young Adults with Cancer (Gen-Y Trial) The 66-gene panel treatment is unique because it uses a comprehensive genetic testing approach to identify hereditary cancer risks in young adults, allowing for ...

2. questdiagnostics.com questdiagnostics.com/healthcare-professionals/about-our-tests/cancer/hereditary-cancer/comprehensive-and-guideline-based-hereditary-cancer-panels

Comprehensive and guideline-based hereditary cancer ... The Comprehensive Hereditary Cancer Panel includes 66 genes associated with a broad spectrum of hereditary cancers.

3. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/gtr/tests/592394/

Comprehensive Hereditary Cancer Panel (66 Genes) - GTR Comprehensive Hereditary Cancer Panel (66 Genes) Clinical Genetic Test. Help offered by Quest Diagnostics Nichols Institute San Juan Capistrano.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12203036/

Changes in multi‐gene cancer panels for children: A 4‐year ... We find that multigene panels show a trend of growing larger in number of genes included over time and explore the utility of additional genetic testing.

5. questdiagnostics.com questdiagnostics.com/healthcare-professionals/about-our-tests/cancer/hereditary-cancer/hereditary-cancer-genetic-testing-menu

Hereditary cancer genetic testing menu The Comprehensive Hereditary Cancer Panel includes 66 genes associated with a broad spectrum of hereditary cancers. This can include, but is not limited to, ...

6. acog.org acog.org/womens-health/faqs/multigene-panel-testing-for-cancer

Multigene Panel Testing for Cancer Multigene panel testing is a type of genetic testing that looks for mutations in several genes at once. This is different from single-gene testing.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5679029/

Multigene Panel Testing for Hereditary Cancer Risk - PMC This article provides an overview of multigene panel testing for hereditary cancer risk and offers two case examples to highlight the clinical considerations.