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

1238 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial uses a broad genetic test and automated computer systems to identify cancer risk in young adult cancer patients and their close relatives. It aims to catch genetic risks that traditional methods might miss, helping doctors manage these risks more efficiently.

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 data supports the effectiveness of the treatment 66-gene panel for young adult cancers?

Research shows that multigene panels can be a cost- and time-effective way to test for multiple genes at once, which can help in understanding cancer risk and guiding management options. This approach has been used effectively in hereditary breast and ovarian cancer to estimate risk and inform treatment decisions. ^{1 2 3 4 5}

Is genetic testing for young adults with cancer generally safe?

The research does not provide specific safety data for genetic testing, but it is widely used in clinical practice for assessing cancer risk, suggesting it is generally considered safe. ^{3 6 7 8 9}

How is the 66-gene panel treatment for young adult cancers different from other treatments?

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 personalized screening and prevention strategies. This differs from traditional single-gene tests by providing a broader analysis of multiple genes, which can lead to more informed and tailored healthcare decisions. ^{3 8 10 11 12}

Research Team

Katherine L Nathanson, MD

Principal Investigator

University of Pennsylvania

Steven Joffe, MD

Principal Investigator

University of Pennsylvania

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

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]

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]

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 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]

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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical Application of Multigene Panels: Challenges of Next-Generation Counseling and Cancer Risk Management. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

Multigene panel testing for hereditary breast and ovarian cancer in the province of Ontario. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Multigene Panel Testing for Hereditary Cancer and Genetic Counseling. [2021]

4. Greece pubmed.ncbi.nlm.nih.gov

Revisiting the Implications of Positive Germline Testing Results Using Multi-gene Panels in Breast Cancer Patients. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Outcomes of large panel genetic evaluation of breast cancer patients in a community-based cancer institute. [2021]

6. Switzerland 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. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Parent opinions regarding the genetic testing of minors for BRCA1/2. [2010]

8. Poland pubmed.ncbi.nlm.nih.gov

Patients with pathogenic variants for breast cancer other than BRCA1 and BRCA2: qualitative interviews about health care experiences. [2022]

9. Poland 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. [2022]

10. Japan pubmed.ncbi.nlm.nih.gov

[Current Status and Challenges of Clinical Practice for Hereditary Tumor Syndromes]. [2019]

11. United States 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. [2022]

12. United States pubmed.ncbi.nlm.nih.gov

Outcomes of disease-specific next-generation sequencing gene panel testing in adolescents and young adults with colorectal cancer. [2020]