A Precision Medicine Approach (SMMART-ACT) for the Treatment of Patients With Advanced Sarcoma, Prostate, Breast, Ovarian or Pancreatic Cancer

NCT06630325 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: STUDY00026643NCI-2024-07664
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Advanced Ovarian Carcinoma; Advanced Pancreatic Carcinoma; Advanced Prostate Carcinoma; Anatomic Stage III Breast Cancer AJCC v8; Stage III Ovarian Cancer AJCC v8; Stage III Pancreatic Cancer AJCC v8; Stage III Prostate Cancer AJCC v8; Stage IV Ovarian Cancer AJCC v8; Stage IV Pancreatic Cancer AJCC v8; Stage IV Prostate Cancer AJCC v8; Advanced Malignant Solid Neoplasm; Advanced Sarcoma; Advanced Breast Carcinoma; Anatomic Stage IV Breast Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Proportion of Participants Who Receive an ACT Therapy Based on a SMMART-ACT Tumor Board Recommendation.

  A threshold of the posterior probability rate of 75% will be utilized for declaring feasibility to support the analysis of the primary objective in this pilot.

  From SMMART-ACT tumor board review to the first dose of ACT study drug per unique treatment regimen. This is expected to take up to approximately 30 days.

Secondary Outcomes (6)

• Incidence of Treatment Emergent Adverse Events (TEAEs) Suspected or Confirmed as Attributed to Study Therapy

  From first dose of study drug to 30 days after last dose of study drug(s). This is expected to be approximately 7 months, but could be shorter if participant stops treatment early for any reason.

• Rate of Treatment Discontinuation Due to Toxicities and/or Intolerability

  From first dose of study drug to last dose of study drug(s). This is expected to be approximately 6 months, but could be shorter if participant stops treatment early for any reason.

• Overall Response Rate (ORR)

  At 24 weeks from cycle 1 day 1

• Progression Free Survival

  From first dose of study drug to first date of documented progression or recurrence (RECIST 1.1), end-of-study, or death due to any cause, whichever occurs first, up to 5 years

• Disease Specific Survival (DSS)

  From first dose of study drug to death as a result of the disease, up to 5 years

Study Arms (7)

Arm I (abemaciclib, gemcitabine)

EXPERIMENTAL

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.

Drug: Abemaciclib; Procedure: Biopsy; Procedure: Bone Scan; Drug: Gemcitabine; Other: Survey Administration; Procedure: Biospecimen Collection

Arm II (abemaciclib, pemetrexed)

EXPERIMENTAL

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.

Drug: Abemaciclib; Procedure: Biopsy; Procedure: Bone Scan; Drug: Pemetrexed; Other: Survey Administration; Procedure: Biospecimen Collection

Arm III (abemaciclib)

EXPERIMENTAL

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.

Drug: Abemaciclib; Procedure: Biopsy; Procedure: Bone Scan; Other: Survey Administration; Procedure: Biospecimen Collection

Arm IV (abemaciclib, exemestane)

EXPERIMENTAL

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.

Drug: Abemaciclib; Procedure: Biopsy; Procedure: Bone Scan; Drug: Exemestane; Other: Survey Administration; Procedure: Biospecimen Collection

Arm V (abemaciclib, letrozole)

EXPERIMENTAL

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.

Drug: Abemaciclib; Procedure: Biopsy; Procedure: Bone Scan; Drug: Letrozole; Other: Survey Administration; Procedure: Biospecimen Collection

Arm VI (abemaciclib, tamoxifen)

EXPERIMENTAL

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.

Drug: Abemaciclib; Procedure: Biopsy; Procedure: Bone Scan; Other: Survey Administration; Drug: Tamoxifen; Procedure: Biospecimen Collection

Arm VII (osimertinib)

EXPERIMENTAL

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.

Procedure: Biopsy; Procedure: Bone Scan; Procedure: Echocardiography; Procedure: Multigated Acquisition Scan; Drug: Osimertinib; Other: Survey Administration; Procedure: Biospecimen Collection

Interventions

Abemaciclib DRUG

Given PO

Also known as: LY 2835219, LY-2835219, LY2835219, Verzenio

Arm I (abemaciclib, gemcitabine); Arm II (abemaciclib, pemetrexed); Arm III (abemaciclib); Arm IV (abemaciclib, exemestane); Arm V (abemaciclib, letrozole); Arm VI (abemaciclib, tamoxifen)

Biopsy PROCEDURE

Undergo tumor biopsy

Also known as: BIOPSY_TYPE, Bx

Arm I (abemaciclib, gemcitabine); Arm II (abemaciclib, pemetrexed); Arm III (abemaciclib); Arm IV (abemaciclib, exemestane); Arm V (abemaciclib, letrozole); Arm VI (abemaciclib, tamoxifen); Arm VII (osimertinib)

Bone Scan PROCEDURE

Undergo bone scan

Also known as: Bone Scintigraphy

Arm I (abemaciclib, gemcitabine); Arm II (abemaciclib, pemetrexed); Arm III (abemaciclib); Arm IV (abemaciclib, exemestane); Arm V (abemaciclib, letrozole); Arm VI (abemaciclib, tamoxifen); Arm VII (osimertinib)

Echocardiography PROCEDURE

Undergo echocardiography

Also known as: EC

Arm VII (osimertinib)

Exemestane DRUG

Given PO

Also known as: Aromasin, FCE-24304

Arm IV (abemaciclib, exemestane)

Gemcitabine DRUG

Given IV

Also known as: dFdC, dFdCyd, Difluorodeoxycytidine

Arm I (abemaciclib, gemcitabine)

Letrozole DRUG

Given PO

Also known as: CGS 20267, CGS-20267, CGS20267, Femara, Fempro

Arm V (abemaciclib, letrozole)

Multigated Acquisition Scan PROCEDURE

Undergo MUGA

Also known as: Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan, MUGA, MUGA Scan, Multi-Gated Acquisition Scan, Radionuclide Ventriculogram Scan, Radionuclide Ventriculography, RNV Scan, RNVG, SYMA Scanning, Synchronized Multigated Acquisition Scanning

Arm VII (osimertinib)

Osimertinib DRUG

Given PO

Also known as: AZD 9291, AZD-9291, AZD9291, Mereletinib

Arm VII (osimertinib)

Pemetrexed DRUG

Given IV

Also known as: MTA, Multitargeted Antifolate, Pemfexy

Arm II (abemaciclib, pemetrexed)

Survey Administration OTHER

Ancillary studies

Arm I (abemaciclib, gemcitabine); Arm II (abemaciclib, pemetrexed); Arm III (abemaciclib); Arm IV (abemaciclib, exemestane); Arm V (abemaciclib, letrozole); Arm VI (abemaciclib, tamoxifen); Arm VII (osimertinib)

Tamoxifen DRUG

Given PO

Also known as: TMX

Arm VI (abemaciclib, tamoxifen)

Biospecimen Collection PROCEDURE

Biological Sample Collection, Biological Sample Collection, Biospecimen Collected, Biospecimen Collection, Specimen Collection

Arm I (abemaciclib, gemcitabine); Arm II (abemaciclib, pemetrexed); Arm III (abemaciclib); Arm IV (abemaciclib, exemestane); Arm V (abemaciclib, letrozole); Arm VI (abemaciclib, tamoxifen); Arm VII (osimertinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• PRE-SCREENING: Written informed consent prior to any Pre-Screening activities, study-specific procedures or interventions
• PRE-SCREENING: At least 18 years of age at time of informed consent. Persons of all gender identities, biological sexes, races, and ethnicities will be included
• PRE-SCREENING: A diagnosis of advanced sarcoma or advanced prostate, breast, ovarian, or pancreatic cancer. Change in an individual's cancer can be tracked objectively according to the Prostate Cancer Working Group 3 (PCWG3) criteria for prostate cancer, and Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 criteria for sarcomas and breast, ovarian, and pancreatic cancers
• PRE-SCREENING: Biospecimen collection, as per institutional standards, must be consented to and collection must be feasible, with the following exceptions for tissue collections:
• Individuals with a prior tumor tissue sample with successful SMMART-Clinical Analytics Platform (CAP) assays, collected within the last 90 days, may be eligible, so long as ≤ 1 treatment has been received within ≤ 90 days of that biopsy
• PRE-SCREENING: Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
• PRE-SCREENING: Physician-assessed life expectancy of ≥ 6 months
• PRE-SCREENING: Additional eligibility criteria specific to their disease must also be met
• PRIMARY TREATMENT: Documented progression after at least 1 line of prior therapy for advanced disease. If recurrence occurred within 6 months of the last dose of an adjuvant/neoadjuvant therapy, that adjuvant/neoadjuvant therapy will count as 1 line of therapy
• PRIMARY TREATMENT: SMMART-ACT tumor board recommendation of at least one SMMART-ACT therapy regimen defined within this protocol, based on the board's review of SMMART-CAP results on a pre-screening biopsy
• PRIMARY TREATMENT: Absolute neutrophil count (ANC) ≥ 1,500/uL (1.5 K/cu mm) (assessed at primary \[post pre-screening\] screening, or by the time that study intervention commences)
• PRIMARY TREATMENT: Platelets ≥ 100,000/uL (100 K/cu mm) (assessed at primary \[post pre-screening\] screening, or by the time that study intervention commences)
• PRIMARY TREATMENT: Hemoglobin ≥ 9 g/dL (or ≥ 5.6 mmol/L) (assessed at primary \[post pre-screening\] screening, or by the time that study intervention commences)
• PRIMARY TREATMENT: Creatinine OR measured or calculated creatinine clearance (glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance \[CrCl\]) ≤ 1.5 x institutional upper limit of normal (ULN) (institutional upper limit of normal \[IULN\]) OR ≥ 50 mL/min/1.73 m\^2 (assessed at primary \[post pre-screening\] screening, or by the time that study intervention commences)
• Creatinine clearance should be calculated per institutional standard. For participants with a baseline calculated creatinine clearance below normal institutional laboratory values, a measured baseline creatinine clearance should be determined. Individuals with higher values felt to be consistent with inborn errors of metabolism will be considered on a case-by-case basis.

You may not qualify if:

• PRE-SCREENING: Evidence of active malignancy of another cancer with a natural history or treatment history that may affect safety or efficacy assessments of this study or impose unacceptable risk to the participant. Guiding examples for those who can be enrolled include: individuals who have been disease free for ≥ two years; cancers with high cure rates (e.g., prior history of stage 1 rectal cancer and currently otherwise disease free); adequately treated, localized nonmelanomatous skin cancer
• PRE-SCREENING: Absence of biopsiable lesion, AND unavailable/insufficient archival tissue
• PRIMARY TREATMENT: Any brain/central nervous system (CNS) metastasis that progresses within ≤ four weeks of CNS directed treatment as ascertained by clinical examination(s) and MRI or CT during the main eligibility screening period
• PRIMARY TREATMENT: One or more new, active brain/CNS metastasis or the presence of known leptomeningeal disease (LMD) that requires immediate treatment. If treatment within the first cycle of therapy is unlikely to be required, enrollment may be considered, as per the investigator
• PRIMARY TREATMENT: Concurrent forms of anti-cancer therapy that have the potential to interfere with efficacy and safety assessments or that may pose increased risk to the participant while on a SMMART-ACT treatment, and as per the investigator (Select hormone therapies are allowed)
• PRIMARY TREATMENT: More than one intervening line of therapy for treatment of their cancer since the time of the pre-screening biopsy, exclusive of most maintenance hormone therapies
• Note: Participants who have a pre-screening biopsy while receiving a standard of care (SOC) treatment will not be eligible if they receive any additional lines of treatment prior to the start of SMMART-ACT treatment. This treatment will count as one line of intervening therapy
• PRIMARY TREATMENT: Uncontrolled intercurrent illness and infection that may interfere with planned treatment, including, but not limited to, the following:
• Symptomatic congestive heart failure (New York Heart Association \[NYHA\] class III or IV),
• Unstable angina pectoris or coronary angioplasty, or stenting within \< six months prior to enrollment,
• Cardiac arrhythmia (ongoing cardiac dysrhythmias of grade ≥ 2 \[National Cancer Institute (NCI) CTCAE v 5.0\]),
• Conditions that require intra-cardiac defibrillators,
• Known cardiac metastases,
• History of abnormal cardiac valve morphology (≥ grade 2),
• Chronic graft versus host disease (GVHD) or immunosuppressive therapy for the control of GVHD

Sponsors & Collaborators

• OHSU Knight Cancer Institute: lead
• Oregon Health and Science University: collaborator
• Eli Lilly and Company: collaborator
• AstraZeneca: collaborator

Study Sites (1)

OHSU Knight Cancer Institute

Portland, Oregon, 97239, United States

Location

MeSH Terms

Conditions

Ovarian Neoplasms; Pancreatic Neoplasms; Prostatic Neoplasms

Interventions

abemaciclib; Biopsy; exemestane; Gemcitabine; Letrozole; osimertinib; Pemetrexed; Tamoxifen

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Digestive System Neoplasms; Digestive System Diseases; Pancreatic Diseases; Genital Neoplasms, Male; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Nitriles; Organic Chemicals; Triazoles; Azoles; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Results Point of Contact

• Title: Gordon Mills, MD, PhD
• Organization: Oregon Health & Science University - Knight Cancer Institute

millsg@ohsu.edu

503-346-4660

Study Officials

• Charles D Lopez, MD, PhD

  OHSU Knight Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 26, 2024
• First Posted: October 8, 2024
• Study Start: June 24, 2025
• Primary Completion: March 11, 2026
• Study Completion: March 11, 2026
• Last Updated: April 28, 2026
• Results First Posted: April 28, 2026

Record last verified: 2026-04

Locations

US (1)