Targeted Therapy Based on Genetic Profile for Cancer

Overseen By Apostolia M. Tsimberidou

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: M.D. Anderson Cancer Center

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

Compensation: Varies

Number of Visits: Unknown

Duration: 2 months to 3 years

1362 Participants Needed

Trial Summary

What is the purpose of this trial?

This randomized clinical trial studies how molecular profiling and targeted therapy work in treating patients with cancer that has spread to other places in the body compared to standard treatment. Information about genetic differences in a patient's tumor can be used to choose treatment that may target the tumor. It is not yet validated whether selecting treatment after studying the genetic changes that are associated with cancer in a patient's tumor is a better way to treat patients with metastatic cancer compared to therapy not based on studying the genetic changes that are associated with cancer.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you have received chemotherapy, surgery, or radiotherapy recently, you must wait 3-4 weeks before starting the study treatment.

What data supports the effectiveness of the treatment Targeted Therapy Based on Genetic Profile for Cancer?

Research shows that using genetic profiling to guide targeted treatments can improve outcomes for cancer patients, especially when specific genetic changes are identified and matched with appropriate therapies. For example, in a study with breast cancer patients, those with certain genetic alterations had better progression-free survival when treated with targeted therapies matched to their genetic profile. ^{1 2 3 4 5}

Is targeted therapy based on genetic profiling generally safe for humans?

Targeted therapy can have a high rate of side effects, especially in certain cancers like metastatic renal cell carcinoma, where genetic differences can predict how severe these side effects might be. However, many targeted therapies are approved by the FDA with guidelines to help manage these risks, and ongoing research aims to improve safety by personalizing treatment based on genetic information. ^{4 6 7 8 9}

How is the Targeted Therapy Based on Genetic Profile for Cancer different from other cancer treatments?

This treatment is unique because it uses molecular profiling to identify specific genetic changes in a person's cancer, allowing for a personalized approach that targets these unique alterations. This precision method contrasts with traditional treatments that are not tailored to individual genetic profiles. ^{10 11 12 13 14}

Research Team

Apostolia M Tsimberidou

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for patients with metastatic cancer who have tried standard treatments or decided not to use them. They should be relatively healthy, able to perform daily activities (ECOG 0-1), and have tumors that can be measured or biopsied. Women of childbearing age and men must agree to contraception during the study. Patients with stable brain metastasis off steroids for two weeks are eligible.

Inclusion Criteria

My tumor can be biopsied or I have a recent tumor sample available.

Absolute neutrophil count >= 1,000/ul

The patient has provided signed informed consent

Exclusion Criteria

Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures

I have not been treated based on genetic testing results.

I haven't had cancer treatment in the last 3 weeks, or I've recovered from its side effects.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Molecular Profiling

Genomic analysis of tumor sample is performed to identify molecular alterations and assign treatment

2-4 weeks

Treatment

Participants receive either matched targeted therapy or standard-of-care therapy based on randomization

2 months to 3 years

Follow-up

Participants are monitored for progression-free survival and other outcomes

Continuous Monitoring

Treatment Details

Interventions

• Standard-of-Care Therapy
• Targeted Therapy Based on Molecular Profiling

Trial Overview The trial compares targeted therapy chosen based on genetic differences in a patient's tumor against standard cancer treatment. It aims to determine if personalized medicine, using information about the tumor's molecular profile, is more effective than traditional approaches not tailored to genetic changes.

Participant Groups

Group I: Arm B: Standard-of-Care Therapy Experimental Treatment 1 Intervention

Standard-of-Care treatment not selected on basis of alteration analysis.

Group II: Arm A: Targeted Therapy Active Control 1 Intervention

Personalized treatment, targeted therapy against the alteration based on molecular profiling.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Tempus AI

Industry Sponsor

Trials

18

Recruited

20,700+

Tempus Labs

Industry Sponsor

Trials

17

Recruited

20,200+

Findings from Research

In a systematic review of 31 sub-trials involving 1637 cancer patients, the overall objective response rate (ORR) for therapies in umbrella trials was 17.7%, indicating that only about one in five patients responded positively to treatment.

The combination of targeted therapies with chemotherapy showed a significantly higher ORR of 39.0% compared to 13.3% for targeted therapies alone, but the overall drug-related death rate was low at 0.8%, suggesting that while umbrella trials may not guarantee increased benefits, they have a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk and benefit for umbrella trials in oncology: a systematic review and meta-analysis. Strzebonska, K., Blukacz, M., Wasylewski, MT., et al.[2023]

Genotype-guided cancer therapy is crucial for personalizing treatment, as it helps to optimize drug exposure and predict potential toxicities, which is especially important given the variability among patients and the narrow therapeutic range of anticancer drugs.

Over a dozen FDA-approved anticancer drugs now include pharmacogenetic biomarkers, and this review emphasizes the need for more prospective clinical trials to enhance the effectiveness of personalized cancer treatments and address existing barriers to their implementation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Application of genotype-guided cancer therapy in solid tumors. Patel, JN.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

The impact of genomic context on outcomes of solid cancer patients treated with genotype-matched targeted therapies: a comprehensive review. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Referrals to a Phase I Clinic and Trial Enrollment in the Molecular Screening Era. [2020]

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

Moving Molecular Profiling to Routine Clinical Practice: A Way Forward? [2021]

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

Next-Generation Sequencing to Guide Clinical Trials. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Genomics to select treatment for patients with metastatic breast cancer. [2023]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Pharmacogenomic Markers of Targeted Therapy Toxicity in Patients with Metastatic Renal Cell Carcinoma. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Risk and benefit for umbrella trials in oncology: a systematic review and meta-analysis. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Application of genotype-guided cancer therapy in solid tumors. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Clinical Application of Targeted Deep Sequencing in Solid-Cancer Patients and Utility for Biomarker-Selected Clinical Trials. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Novel points of attack for targeted cancer therapy. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Molecular screening program to select molecular-based recommended therapies for metastatic cancer patients: analysis from the ProfiLER trial. [2023]

12. Australia pubmed.ncbi.nlm.nih.gov

Precision oncology using a clinician-directed, tailored approach to molecular profiling. [2018]

13. Germany pubmed.ncbi.nlm.nih.gov

Cancer Evolution as the New Frontier of Precision Medicine. [2019]

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

Database of genomic biomarkers for cancer drugs and clinical targetability in solid tumors. [2022]