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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method for treating certain advanced cancers, such as sarcoma, prostate, breast, ovarian, or pancreatic cancer, using a personalized medicine approach called SMMART-ACT. Researchers will use genetic and protein tests to monitor how the cancer evolves and recommend specific treatments based on these changes. The trial includes multiple treatment groups, each testing different drug combinations to identify the most effective option. Individuals with advanced forms of these cancers who have already tried at least one other treatment might be suitable candidates for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

In a previous study, the combination of abemaciclib with hormone therapies like exemestane and letrozole was safe for patients with advanced breast cancer. Patients experienced fewer serious side effects, and the treatment was generally well-tolerated.

Research has shown that fulvestrant, used to treat certain breast cancers, is also well-tolerated. Common side effects include nausea and tiredness, but severe reactions are rare.

Studies on olaparib, a cancer treatment drug, indicate it can be safe for long-term use. However, it may cause bone marrow issues for some people. When combined with drugs like carboplatin and paclitaxel, it was well-tolerated in the past.

For the combination of olaparib and liposomal doxorubicin, previous studies found it to be generally safe, with manageable side effects.

Abemaciclib, when used with gemcitabine or pemetrexed, has shown a safety profile that patients can handle well.

Gefitinib combined with pemetrexed and carboplatin was also safe for patients with non-small cell lung cancer, with better outcomes compared to gefitinib alone.

Lastly, osimertinib has been noted for causing some serious side effects like lung problems, but these are uncommon.

This Phase 2 trial aims to confirm these findings by further exploring the safety of these drug combinations in different types of cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the Precision Medicine Approach for Cancer because it tailors treatment options based on individual genetic profiles, potentially increasing effectiveness and reducing side effects. Unlike standard treatments, which often apply a one-size-fits-all approach, this strategy uses a variety of drugs, such as abemaciclib, olaparib, and gefitinib, each targeting specific pathways involved in cancer growth. This personalized approach allows for combinations like abemaciclib with exemestane for hormone-driven cancers or olaparib with carboplatin and paclitaxel for DNA repair deficiencies, offering new hope for better outcomes in patients with specific genetic markers.

What evidence suggests that this trial's treatments could be effective for advanced cancer?

Research has shown that the treatments tested in this trial have potential in treating various types of cancer. Participants may receive abemaciclib combined with exemestane or letrozole, which studies have found can lead to positive outcomes, with 78% of patients experiencing stable disease and some seeing their tumors shrink or disappear. Another treatment option is fulvestrant, which the FALCON trial showed helps patients live longer without their cancer worsening, especially those who haven't had hormone therapy before. Participants may also receive olaparib, either alone or with other drugs like carboplatin or paclitaxel, which has been effective in slowing ovarian cancer progression. Additionally, combining olaparib with liposomal doxorubicin is another treatment arm in this trial and has shown encouraging results in preventing cancer from worsening. These findings suggest these treatments could be effective for advanced cancers, including those studied in this trial. ^{6 7 8 9 10}

Who Is on the Research Team?

Lara Davis, MD

Principal Investigator

OHSU Knight Cancer Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12513154/

Prevalence and prognosis of patients with breast cancer ... ... trial suggests no evidence to support use of adjuvant abemaciclib in women with breast cancer. Lancet Oncol. 2023;24(6):589–593. doi ...

2. onclive.com onclive.com/view/abemaciclib-plus-endocrine-therapy-provides-os-benefit-in-hr-her2-negative-breast-cancer

Abemaciclib Plus Endocrine Therapy Provides OS Benefit ... Abemaciclib plus endocrine therapy reduced death risk by 15.8% in high-risk early breast cancer patients compared to endocrine therapy alone.

3. verzenio.lilly.com verzenio.lilly.com/hcp/efficacy-early-breast-cancer

Verzenio® + ET for Early Breast Cancer | Efficacy - Eli Lilly At Month 24, Verzenio plus ET was 92.6% vs ET alone at 89.4%—a 2-year delta of 3.2%. At Month 36, Verzenio plus ET was 88.9% vs ET alone at 83.7%—a 3-year delta ...

4. appliedclinicaltrialsonline.com appliedclinicaltrialsonline.com/view/verzenio-kisqali-positive-long-term-results-early-breast-cancer-trials

Verzenio and Kisqali Deliver Positive Long-Term Results ... Kisqali, in the NATALEE trial, achieved a 28.4% reduction in recurrence risk and a five-year IDFS rate of 85%, demonstrating long-term benefits ...

5. cancernetwork.com cancernetwork.com/view/abemaciclib-endocrine-therapy-improves-os-in-hr-her2-early-breast-cancer

Abemaciclib/Endocrine Therapy Improves OS in HR+/HER2 Results from the monarchE study showed a statistically significant OS improvement with abemaciclib plus ET for patients with HR+/HER2– early ...

6. verzenio.lilly.com verzenio.lilly.com/hcp/safety-adverse-reactions

Adverse Reactions | HCP Safety | Verzenio (abemaciclib) In clinical trials, deaths due to VTE have been reported in patients treated with Verzenio. Verzenio has not been studied in patients with early breast cancer ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7990838/

Safety and efficacy of abemaciclib plus endocrine therapy ... The safety profile together with the established efficacy of abemaciclib supports a favorable clinical benefit/risk ratio overall in patients with HR+, HER2− ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2017/208716Orig1s000RiskR.pdf

208716Orig1s000 - accessdata.fda.gov 5 Risk Assessment & Safe-Use Conditions. The safety profile of abemaciclib for the proposed indications is based on safety data from the Phase 3.

9. mayoclinic.org mayoclinic.org/drugs-supplements/abemaciclib-oral-route/description/drg-20406567

Abemaciclib (oral route) - Side effects & dosage It interferes with the growth of cancer cells, which are eventually destroyed. Since the growth of normal cells may also be affected by the medicine, other ...

10. ascopubs.org ascopubs.org/doi/10.1200/JCO.20.02514

Abemaciclib Combined With Endocrine Therapy for the ... OS data were immature, with 39 (1.4%) deaths observed in the abemaciclib arm and 37 (1.3%) observed in the control arm. The study will continue ...