Precision Medicine Approach for Cancer

Recruiting at 1 trial location

Overseen By Knight Cancer Institute Clinical Trials Information

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: OHSU Knight Cancer Institute

Must not be taking: Concurrent anti-cancer therapy

Disqualifiers: Active malignancy, Brain metastasis, Hepatitis C, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 6-8 months

30 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, it mentions that concurrent forms of anti-cancer therapy that might interfere with the study are not allowed, except for some hormone therapies. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the treatment SMMART-ACT in the Precision Medicine Approach for Cancer?

Precision medicine in cancer care uses detailed information about a person's tumor to tailor treatments, which can improve effectiveness and reduce side effects. Research shows that using targeted therapies based on molecular profiling can lead to better outcomes, as seen in some small clinical trials and ongoing studies. ^{1 2 3 4 5}

What safety data exists for the precision medicine approach for cancer treatment?

Research on small molecule kinase inhibitors (a type of cancer treatment) has shown that they can have various adverse events (unwanted side effects) in patients. A machine-learning model has been developed to predict these side effects, helping to identify and manage potential safety risks for individual patients. ^{6 7 8 9 10}

How is the SMMART-ACT treatment different from other cancer treatments?

SMMART-ACT is unique because it uses a precision medicine approach, which involves analyzing the genetic makeup of a patient's tumor to tailor treatments specifically to their cancer's molecular profile. This method aims to improve treatment effectiveness and reduce side effects by targeting the specific genetic alterations present in the tumor, rather than using a one-size-fits-all approach. ^{2 11 12 13 14}

What is the purpose of this trial?

This phase II trial tests the how well a precision medicine approach (serial measurements of molecular and architectural response to therapy \[SMMART\])-adaptive clinical treatment \[ACT\]) works in treating patients with sarcoma, prostate, breast, ovarian or pancreatic cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). SMMART testing uses genetic and protein tests to learn how cancer changes and to understand what drugs may work against a person's cancer or why drugs stop working. These test results are reviewed by a group of physicians and scientists during a SMMART tumor board who then recommend precision therapy.

Research Team

Lara Davis, MD

Principal Investigator

OHSU Knight Cancer Institute

Eligibility Criteria

This trial is for patients with advanced sarcoma, prostate, breast, ovarian or pancreatic cancer that has spread. Participants must have a type of cancer that's eligible and be willing to undergo various treatments and tests as part of the precision medicine approach.

Inclusion Criteria

I can do most of my daily activities by myself.

Consented biospecimen collection as per institutional standards, with exceptions for prior successful SMMART-CAP assays

Physician-assessed life expectancy of ≥ 6 months

Exclusion Criteria

I am not on any cancer treatments that could affect the trial's safety or results.

I cannot or will not take pills for the study.

History of allergy to an assigned study agent or its excipients

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive personalized advanced cancer treatment based on SMMART-ACT tumor board recommendations. Treatment involves various drug regimens across 14 arms, with cycles repeating every 21 or 28 days for up to 6-8 cycles.

6-8 months

Regular visits for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up includes regular assessments every 3 months for 1 year, then every 6 months until year 5.

5 years

Follow-up visits every 3-6 months

Treatment Details

Interventions

• SMMART-ACT

Trial Overview The trial is testing a precision medicine method called SMMART-ACT. It involves genetic and protein tests to tailor treatment based on how the cancer responds. Treatments include drugs like Exemestane, Gefitinib, Gemcitabine, among others.

Participant Groups

Group I: Arm XIV (osimertinib) Experimental Treatment 7 Interventions

Patients receive osimertinib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography or MUGA scan and blood sample collection throughout the study. Patients also undergo tumor biopsy on study and optionally at the end of treatment. Additionally, prostate cancer patients undergo bone scan on study.

Group II: Arm XIII (olaparib, liposomal doxorubicin) Experimental Treatment 8 Interventions

Patients receive olaparib PO BID on days 1-28 and liposomal doxorubicin IV on day 1 of each cycle. Cycles repeat every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography or MUGA scan and blood sample collection throughout the study. Patients also undergo tumor biopsy on study and optionally at the end of treatment. Additionally, prostate cancer patients undergo bone scan on study.

Group III: Arm XII (olaparib, carboplatin, paclitaxel) Experimental Treatment 7 Interventions

Patients receive olaparib PO BID on days 1-3, 8-10, 15-17, 21-23 and carboplatin IV and paclitaxel IV on days 1, 8 and 15 of each cycle. Cycles repeat every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the study. Patients also undergo tumor biopsy on study, as clinically indicated, and optionally at the end of treatment. Additionally, prostate cancer patients undergo bone scan on study.

Group IV: Arm XI (olaparib) Experimental Treatment 5 Interventions

Patients receive olaparib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the study. Patients also undergo tumor biopsy on study and optionally at the end of treatment. Additionally, prostate cancer patients undergo bone scan on study.

Group V: Arm X (gefitinib) Experimental Treatment 5 Interventions

Patients receive gefitinib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the study. Patients also undergo tumor biopsy on study and optionally at the end of treatment. Additionally, prostate cancer patients undergo bone scan on study.

Group VI: Arm VIII (olaparib, temozolomide) Experimental Treatment 6 Interventions

Patients receive olaparib PO BID and temozolomide PO QD on days 1-7 of each cycle. Cycles repeat every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the study. Patients also undergo tumor biopsy on study and optionally at the end of treatment. Additionally, prostate cancer patients undergo bone scan on study.

Group VII: Arm VII (gefitinib, pemetrexed, carboplatin) Experimental Treatment 7 Interventions

Patients receive gefitinib PO QD on days 1-21, pemetrexed IV on day 1 of each cycle and carboplatin IV on day 1 of cycles 1-6. Cycles repeat every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the study. Patients also undergo tumor biopsy on study and optionally at the end of treatment. Additionally, prostate cancer patients undergo bone scan on study.

Group VIII: Arm VI (abemaciclib, tamoxifen) Experimental Treatment 6 Interventions

Patients receive abemaciclib PO BID and tamoxifen PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the study. Patients also undergo tumor biopsy on study and optionally at the end of treatment. Additionally, prostate cancer patients undergo bone scan on study.

Group IX: Arm V (abemaciclib, letrozole) Experimental Treatment 6 Interventions

Patients receive abemaciclib PO BID and letrozole PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the study. Patients also undergo tumor biopsy on study and optionally at the end of treatment. Additionally, prostate cancer patients undergo bone scan on study.

Group X: Arm IX (fulvestrant) Experimental Treatment 4 Interventions

Patients receive fulvestrant IM on days 1, 15 and 29 of cycle 1 and day 1 of subsequent cycles. Cycles repeat every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the study. Patients also undergo tumor biopsy on study and optionally at the end of treatment. Additionally, prostate cancer patients undergo bone scan on study.

Group XI: Arm IV (abemaciclib, exemestane) Experimental Treatment 6 Interventions

Patients receive abemaciclib PO BID and exemestane PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the study. Patients also undergo tumor biopsy on study and optionally at the end of treatment. Additionally, prostate cancer patients undergo bone scan on study.

Group XII: Arm III (abemaciclib) Experimental Treatment 5 Interventions

Patients receive abemaciclib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the study. Patients also undergo tumor biopsy on study and optionally at the end of treatment. Additionally, prostate cancer patients undergo bone scan on study.

Group XIII: Arm II (abemaciclib, pemetrexed) Experimental Treatment 6 Interventions

Patients receive abemaciclib PO BID on days 1-21 and pemetrexed IV over 10 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the study. Patients also undergo tumor biopsy on study and optionally at the end of treatment. Additionally, prostate cancer patients undergo bone scan on study.

Group XIV: Arm I (abemaciclib, gemcitabine) Experimental Treatment 6 Interventions

Patients receive abemaciclib PO BID on days 1-21 and gemcitabine IV over 30 minutes on days 1 and 8 of each cycle. Cycles repeat every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the study. Patients also undergo tumor biopsy on study and optionally at the end of treatment. Additionally, prostate cancer patients undergo bone scan on study.

Who Is Running the Clinical Trial?

OHSU Knight Cancer Institute

Lead Sponsor

Trials

239

Recruited

2,089,000+

Oregon Health and Science University

Collaborator

Trials

1,024

Recruited

7,420,000+

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Eli Lilly and Company

Industry Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Findings from Research

Precision medicine in cancer treatment is advancing with targeted therapies and companion diagnostic tests that help identify patients who will benefit most, although large-scale randomized trials are still needed to confirm their effectiveness.

Melanoma serves as a key example of how understanding molecular drivers can lead to effective targeted therapies and immune system activation, paving the way for future treatments that are highly specific and less toxic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Precision cancer medicine: the future is now, only better. Tsimberidou, AM., Eggermont, AM., Schilsky, RL.[2022]

A machine-learning model was developed using data from 4638 patients across 16 FDA-approved small molecule kinase inhibitors (SMKIs) to analyze the relationship between kinase targets and adverse events (AEs), providing a new tool for predicting safety risks in cancer treatments.

The model not only helps identify potential kinase-inhibitor adverse event pairs but also serves as a precision medicine tool to enhance patient safety by forecasting clinical safety signals and aiding in the development of safer SMKI therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decoding kinase-adverse event associations for small molecule kinase inhibitors. Gong, X., Hu, M., Liu, J., et al.[2022]

The ADEStrata approach, developed in this study, allows for the stratification of tumor mutations based on adverse drug events (ADEs), specifically focusing on musculoskeletal adverse events in breast cancer patients treated with aromatase inhibitors, using data from 212 patients.

By prioritizing somatic variants linked to ADEs, the study found that this method can identify high-risk patients who may experience poor outcomes, suggesting that it could help tailor cancer therapies to improve patient safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Drug Event-based Stratification of Tumor Mutations: A Case Study of Breast Cancer Patients Receiving Aromatase Inhibitors. Wang, C., Zimmermann, MT., Prodduturi, N., et al.[2018]

A new coding framework was developed and validated to identify severe acute toxicities in colon cancer patients treated with systemic anti-cancer therapy (SACT), showing a 26.4% toxicity rate in adjuvant therapy and 53.4% in metastatic cases.

The framework revealed that specific SACT regimens, such as those including bevacizumab, were associated with higher rates of severe toxicities like bleeding and gastrointestinal issues, highlighting the importance of monitoring these effects in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and validation of a coding framework to identify severe acute toxicity from systemic anti-cancer therapy using hospital administrative data. Boyle, JM., Cowling, TE., Kuryba, A., et al.[2022]

The MASTER precision oncology network shows that using whole-genome/exome and RNA sequencing can lead to targeted treatments for patients with advanced rare cancers, which are often poorly understood.

This approach has been beneficial for a significant number of patients, highlighting the potential for future clinical trials to further explore these personalized treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interdisciplinary team science to understand and intercept rare cancers. Fröhling, S.[2022]

References

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

Precision Medicine: Accelerating the Science to Revolutionize Cancer Care . [2018]

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

Towards Precision Medicine in the Clinic: From Biomarker Discovery to Novel Therapeutics. [2018]

3. England pubmed.ncbi.nlm.nih.gov

NCT/DKFZ MASTER handbook of interpreting whole-genome, transcriptome, and methylome data for precision oncology. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Probabilistic modeling of personalized drug combinations from integrated chemical screen and molecular data in sarcoma. [2020]

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

Precision cancer medicine: the future is now, only better. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Decoding kinase-adverse event associations for small molecule kinase inhibitors. [2022]

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

Adverse Drug Event-based Stratification of Tumor Mutations: A Case Study of Breast Cancer Patients Receiving Aromatase Inhibitors. [2018]

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

Gender differences in adverse events related to Osimertinib: a real-world pharmacovigilance analysis of FDA adverse event reporting system. [2023]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Development and validation of a coding framework to identify severe acute toxicity from systemic anti-cancer therapy using hospital administrative data. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Adverse Event Circumstances and the Case of Drug Interactions. [2020]

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

Precision oncology based on omics data: The NCT Heidelberg experience. [2022]

12. England pubmed.ncbi.nlm.nih.gov

PRECISION: the Belgian molecular profiling program of metastatic cancer for clinical decision and treatment assignment. [2022]

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

Interdisciplinary team science to understand and intercept rare cancers. [2022]

14. England pubmed.ncbi.nlm.nih.gov

The European Society for Medical Oncology (ESMO) Precision Medicine Glossary. [2022]