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

Brief summary public domain (ClinicalTrials.gov)

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.

Detailed description public domain (ClinicalTrials.gov)

PRIMARY OBJECTIVE: I. Feasibility of utilizing a SMMART-adaptive clinical treatment (ACT) tumor board to select personalized advanced cancer treatment plans based on a pre-determined set of drug agents with recommended phase 2 doses (RP2Ds). SECONDARY OBJECTIVES: I. Safety and tolerability of assigned ACT intervention per cancer type. II. Preliminary indications of efficacy based on disease-specific responses. III. Estimated survival benefit per cancer type. EXPLORATORY OBJECTIVES: I. Durability of response compared to the most recent therapy on which progression occurred. II. Changes in ability to conduct activities of daily living (ADL). III. Changes in quality of life (QoL). IV. Feasibility of SMMART-centric assessments of ongoing responses to treatment to identify mechanisms of therapy induced change, per investigator discretion. Such mechanisms may include, but will not be limited to, the following: IVa. Changes in tumor and tumor ecosystem biology; IVb. Response and resistance to therapy. OUTLINE: Patients are assigned to 1 of 14 arms. Participants may re-enter the study and receive a new arm assignment in the event of progressive disease or unacceptable toxicity. ARM I: Patients receive abemaciclib orally (PO) twice per day (BID) on days 1-21 and gemcitabine intravenously (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. ARM II: 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 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. ARM III: 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. ARM IV: Patients receive abemaciclib PO BID and exemestane PO once per day (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. ARM V: 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. ARM VI: 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.

Detailed description public domain (ClinicalTrials.gov)

ARM VII: 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. After completion of study treatment, patients are followed up 30 days, every 3 months for 1 year then every 6 months until year 5.

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

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

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

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.].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

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.].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Overall Response Rate (ORR) [At 24 weeks from cycle 1 day 1].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

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].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Disease Specific Survival (DSS) [From first dose of study drug to death as a result of the disease, up to 5 years].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Overall Survival [From first dose of study drug to date of death from any cause, up to 5 years].