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.
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. ARM VII: 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. ARM VIII: 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. ARM IX: Patients receive fulvestrant intramuscularly (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. ARM X: 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. ARM XI: 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 tumor biopsy, CT scan, MRI scan, PET scan and/or bone scan and blood sample collection throughout the study. Additionally, prostate cancer patients undergo bone scan on study. ARM XII: 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. ARM XIII: 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 multigated acquisition (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. ARM XIV: 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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Given PO
Undergo tumor biopsy
Undergo bone scan
Given IV
Undergo echocardiography
Given PO
Given IM
Given PO
Given IV
Given PO
Undergo MUGA
Given PO
Given PO
Given IV
Given IV
Given IV
Ancillary studies
Given PO
Given PO
Biological Sample Collection, Biological Sample Collection, Biospecimen Collected, Biospecimen Collection, Specimen Collection
OHSU Knight Cancer Institute
Portland, Oregon, United States
Proportion of participants who receive an adaptive clinical treatment (ACT) therapy based serial measurements of molecular and architectural responses to therapy (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.
Time frame: 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.
Incidence of treatment emergent adverse events (TEAEs) suspected or confirmed as attributed to study therapy
The incidence of TEAEs experienced that are suspected or confirmed as attributable to a study drug or procedure will be tabulated
Time frame: 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
The incidence of discontinuation from study therapy due to intolerability and/or toxicities will be reported.
Time frame: 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)
ORR is defined as complete response + partial response. Will be assessed per Response Evaluation Criteria in Solid Tumors (RECIST). An exact 95% confidence interval will be provided.
Time frame: At 24 weeks from cycle 1 day 1
Progression free survival
Will be estimated using the Kaplan-Meier method.
Time frame: 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)
Will be estimated using the Kaplan-Meier method. Analysis will also fit DSS and subdistribution hazard models for both DSS death and non-DSS death.
Time frame: From first dose of study drug to death as a result of the disease, up to 5 years
Overall survival
Will be summarized descriptively using the Kaplan-Meier method. The median and 95% confidence interval will be included in the estimations, if possible.
Time frame: From first dose of study drug to date of death from any cause, up to 5 years
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