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AzTrials

Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 PositivePhase 1NCT03878524

Serial Measurements of Molecular and Architectural Responses to Therapy (SMMART) PRIME Trial

A Phase 1 study testing Abemaciclib, Abiraterone and Afatinib in people with Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive and Anatomic Stage IV Breast Cancer AJCC v8, run by OHSU Knight Cancer Institute at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

This phase Ib trial determines if samples from a patient's cancer can be tested to find combinations of drugs that provide clinical benefit for the kind of cancer the patient has. Read more about this study

Who is it for?
Ages 21 years and older
What is being tested?
Abemaciclib, Abiraterone and Afatinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
2 participants
Where
1 siteUnited States
Study dates
1 Apr 2020to 10 Dec 2020
Phase
Phase 1

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 21 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Ability to understand and the willingness to sign a written informed consent document
  • Participants >= 21 years old at time of informed consent. Both men and women and members of all races and ethnic groups will be included
  • Participants, both men and women, must agree to use an adequate method of contraception prior to study entry, for the duration of study participation, and for 4 months after completion of study
  • Women of childbearing potential must have a negative serum or urine pregnancy test within 14 days prior to start of study drug administration
  • Patients must have a histologically or cytologically-confirmed metastatic solid tumor or hematological malignancy that has progressed as follows:
  • Patients with a solid tumor must have metastatic disease and have progressed on at least 1 line of established therapy that is known to provide clinical benefit, or for whom no standard curative therapy exists. Participants with newly diagnosed, unresectable, locally-advanced or metastatic pancreatic adenocarcinoma and are beginning first-line treatment with a course of chemotherapy are eligible OR
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  • Participants must have a hematological malignancy that is advanced, relapsed, or refractory to at least 1 line of established therapy that is known to provide clinical for the treatment of their disease. Hematological disease included in this study are as follows:
  • Acute myelogenous leukemia (AML), or
  • Myelodysplastic syndrome (MDS), or
  • MDS/myeloproliferative neoplasms (MDS/MPN), or
  • Primary myelofibrosis (PMF)
  • Acute lymphoblastic leukemia (ALL)
  • Chronic myelogenous leukemia (CML)
  • Non-Hodgkin lymphoma (NHL) or Hodgkin's disease (HD)
  • Chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL)
  • Multiple myeloma (MM)
  • Participants with a metastatic solid tumor or advanced hematological malignancy whom, due to medical issues cannot receive standard therapy shown to prolong survival, will be eligible, if other eligibility criteria are met
  • Patients with a metastatic solid tumor or advanced hematological malignancy that actively refuse chemotherapy that is considered standard treatment for their cancer, despite being informed by the investigator about the treatment options, are eligible for this study on a case-by-case basis (in consultation with the principal investigator [PI]). Potential participants actively refusing chemotherapy must have had progression or refractory disease prior to starting study treatment, and their refusal must be documented
  • Participants must have measurable disease:
  • Patients with solid tumors must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. At least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan, per RECIST (v1.1)
  • Note: Participants with lesions on a bone scan that are considered distinctly metastatic will also be included
  • Patients with lymphoma must have at least one non-irradiated tumor mass > 15 mm (long axis of lymph node) or > 10 mm (short axis of lymph node or extranodal lesions) on spiral CT-scan
  • Patients with CLL must have presence of radiographically measurable lymphadenopathy (defined as the presence of >= 1 nodal lesion that measures >= 2.0 cm in the longest diameter [LD] and >= 1.0 cm in the longest perpendicular diameter [LPD] as assessed by CT or magnetic resonance imaging [MRI])
  • Patients with MM must have at least one of the following: serum monoclonal component > 1 g/dL (IgG), or > 0.5 g/dL (IgA), or Bence-Jones (BJ) proteinuria > 200 mg/24 hour, or measurable plasmacytoma (not previously irradiated)
  • Participants with a hematological malignancy must have their bone marrow biopsy and aspirate reviewed at Oregon Health \& Science University (OHSU)
  • Participants with a solid tumor must have lesions meeting the above criteria also and must be amenable to biopsy procedures performed per institutional standards
  • Participants must not currently be receiving any other investigational agents
  • Participants must have Eastern Cooperative Oncology Group (ECOG) performance status =< 2 and a physician assessed life expectancy of >= 6 months
  • Absolute neutrophil count (ANC) >= 1,500/mcL (at time of registration and within 4 weeks prior to initiating on-protocol treatment)
  • Waived for those with hematological malignancy; and may be waived on a case-by-case basis for patient populations recognized to have normal baseline values below this level
  • Platelets >= 100,000/mcL (at time of registration and within 4 weeks prior to initiating on-protocol treatment)
  • Waived for those with hematological malignancy
  • Hemoglobin >= 9 g/dL or >= 5.6 mmol/L (at time of registration and within 4 weeks prior to initiating on-protocol treatment)
  • Waived for those with hematological malignancy
  • Creatinine =< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) >= 60 mL/min/1.73 m^2 for participants with creatinine levels > 1 x institutional ULN (at time of registration and within 4 weeks prior to initiating on-protocol treatment)
  • Waived for those with hematological malignancy; and may be waived on a case-by-case basis for patient populations recognized to have normal baseline values below this level
  • Total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for participants with total bilirubin levels > 1.5 x ULN (at time of registration and within 4 weeks prior to initiating on-protocol treatment)
  • 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
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x ULN (at time of registration and within 4 weeks prior to initiating on-protocol treatment)
  • International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants (at time of registration and within 4 weeks prior to initiating on-protocol treatment)
  • Activated partial thromboplastin time (aPTT) or PTT =< 1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants (at time of registration and within 4 weeks prior to initiating on-protocol treatment)
  • Body mass index (BMI) > > 16.0 and < 35.0 kg/m^2 (at time of registration and within 4 weeks prior to initiating on-protocol treatment)
  • Participants with a BMI of >= 30.0 will use ideal body weight indices in calculating the delivery of agents that are dosed based upon body surface area (i.e., mg agent/meter squared) or weight (i.e., mg agent/kg body weight)
  • Any prior therapy, radiotherapy (except palliative radiation therapy of 30 Gy or less), or major surgery must have been completed >= 4 weeks prior to start of study treatment. All adverse events due to prior therapy must have resolved to a grade 1 or better (except alopecia and lymphopenia for all disease cohorts, and hematologic toxicity for those with a hematological malignancy) by start of treatment. Palliative radiation therapy must have been completed at least 2 weeks prior to start of treatment. The radiotherapy must not be to a lesion that is included as measurable disease
  • Additional cancer-specific inclusion criteria must also be met

Who cannot join

  • Participants with metastases to the central nervous system that are considered uncontrolled and/or were diagnosed within the past 4 weeks of screening for this study
  • Participants cannot have an active malignancy of another cancer. Those with a history of prior malignancy will be considered on a case-by-case basis. Guiding examples for those who can be enrolled include: individuals who have been disease free for > 5 years; individuals who are considered to have a high likelihood of being cured (e.g., prior history of stage 1 rectal cancer and currently otherwise disease free); adequately treated localized non-melanomatous skin cancer
  • Participants cannot be on other forms of anti-cancer therapy at the same time, except as described within this protocol. There must be at least a washout period that accounts for 5 half-lives (or >= 21 days, whichever is longer) of last therapy
  • Participants with prostate cancer (PCa) will continue treatment with androgen deprivation therapy, either by prior castration or treatment with luteinizing hormone-releasing hormone (LHRH) antagonists or agonists, as is standard practice
  • Participants with breast cancer (BCa) who are HER2 positive may continue to receive anti-HER2 therapy per standard practice guidelines, while participants who are hormone receptor positive may continue to receive hormone therapy per standard practice guidelines
  • Participants with a hematological malignancy may continue to receive hydroxyurea or other hypomethylating agent for two cycles of SMMART-PRIME therapy, as described in this protocol
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  • Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia, myocardial infarction within 6 months prior to enrollment, New York Heart Association (NYHA) class III or IV heart failure
  • Chronic graft versus host disease (GVHD) or on immunosuppressive therapy for the control of GVHD
  • Participants with uncontrolled infection will not be enrolled until infection is treated
  • Participant is seropositive with human immunodeficiency virus (HIV) or has active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV)
  • HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
  • For patients with evidence of chronic HBV infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
  • Individuals with a history of HCV infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
  • Participants with medical conditions, inclusive of psychiatric, that in the opinion of the investigators would jeopardize the patient or the study will be excluded
  • Participants that are pregnant or breast feeding
  • ON-TREATMENT: Individuals that have medical and/or psychiatric conditions that in the opinion of investigators would jeopardize participant safety or study integrity if they were to receive on-study treatment will not proceed further treatment and will be removed from study
  • ON-TREATMENT: If performance status is ECOG > 2
  • ON-TREATMENT: History of allergic reaction to a recommended study agent or its excipients
  • Additional cancer-specific exclusion criteria requirements

Trial locations and contacts

1 site in 1 country.

United States1 site

  • OHSU Knight Cancer Institute

    Portland, Oregon, 97239

Other trials in United States

About this study

Official title: Serial Measurements of Molecular and Architectural Responses to Therapy (SMMART) Trial: PRIME

This phase Ib trial determines if samples from a patient's cancer can be tested to find combinations of drugs that provide clinical benefit for the kind of cancer the patient has. This study is also being done to understand why cancer drugs can stop working and how different cancers in different people respond to different types of therapy.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To determine the feasibility of implementing an individualized treatment strategy for advanced solid tumor and hematological malignancies based upon a comprehensive assessment of tumor and patient characteristics.

SECONDARY OBJECTIVES:

  1. To describe the tolerability of implementing an individualized treatment strategy, particularly by measuring unanticipated toxicity associated with the administration of different combinations of two therapeutic agents given to an individual participant.

II. To assess the duration of treatment for participants receiving Serial Measurements of Molecular and Architectural Responses to Therapy (SMMART)-PRIME Therapy #1.

III. To determine overall survival of participants with advanced solid tumors and hematological malignancies.

IV. To determine the time to decline in a participant's ability to perform activities of daily living.

EXPLORATORY OBJECTIVES:

  1. To measure quality of life among enrolled participants. II. To evaluate immune-mediated tumor response among participants receiving an immunomodulatory study drug.

III. To determine the rates of response and benefit to SMMART-PRIME Therapy #1, as an individualized treatment strategy for participants with advanced solid tumor and hematological malignancies.

IV. To determine the progression-free and disease-free survival of participants with advanced solid tumors and hematological malignancies.

OUTLINE:

TUMOR BIOPSY: Patients undergo collection of tissue samples. Clinical analytics are performed on the samples and analyzed by a clinical tumor board to recommend a treatment option based on those analytics. The findings from these Clinical Study Analytics are intended to provide the basis for selection of two drugs that, when administered in combination, provide an optimal and individualized treatment approach. This may or may not include a SMMART-PRIME treatment. The decision to initiate any SMMART-PRIME Therapy ultimately resides with the treating physician in conjunction with the study participant.

SMMART-PRIME TREATMENT: Patients receive a combination of 2 drugs (Drug A and Drug B, selected from interventions below). Doses will be escalated within individual patients over time. As described in detail below, escalation will occur on a monthly basis and is anticipated to occur as follows: first month -- 100% Food and Drug Administration (FDA) approved dose Drug A + 25% FDA approved dose Drug B; second month -- 100% dose Drug A + 50% dose Drug B; third month -- 100% dose Drug A + 100% dose Drug B. All dose-escalations will be reviewed and approved by an independent consultant outside of Oregon Health \& Science University (OHSU).

Treatment will continue for up to the end of 6 treatment cycles (cycle length is between 21-28 days) in the absence of disease progression or unacceptable toxicity. Patients whose treatment is discontinued as a result of excess toxicity or lack of efficacy may switch to a different combination of drugs. Beyond six cycles, participants will be considered off-protocol directed treatment, and will move into long term follow-up.

After completion of study treatment, patients are followed for up to 5 years.

Being tested
Abemaciclib, Abiraterone, Afatinib, Bevacizumab, Bicalutamide
Medical subject headings
Leukemia, Myeloid, Accelerated Phase, Anemia, Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative, Blast Crisis, Leukemia, Myeloid, Chronic-Phase, Breast Neoplasms, Neoplasm Metastasis, Thrombocytosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AbemaciclibDrug

    Also called LY-2835219, LY2835219, Verzenio

    Given PO

  • AbirateroneDrug

    Also called CB 7598

    Given PO

  • AfatinibDrug

    Also called BIBW 2992, BIBW2992

    Given PO

  • BevacizumabBiological

    Also called ABP 215, Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF rhuMAb

    Given IV

  • BicalutamideDrug

    Also called Casodex, Cosudex, ICI 176,334, ICI 176334

    Given PO

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Specimen Collection

    Undergo collection of biospecimens (including tissue, blood, or previously collected archival specimens)

  • BortezomibDrug

    Also called [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid, LDP 341, MLN341, PS-341

    Given IV

  • CabazitaxelDrug

    Also called Jevtana, RPR-116258A, Taxoid XRP6258, XRP-6258

    Given IV

  • CabozantinibDrug

    Given PO

  • CapecitabineDrug

    Also called Ro 09-1978/000, Xeloda

    Given PO

  • CarboplatinDrug

    Also called Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino

    Given IV

  • CelecoxibDrug

    Also called Benzenesulfonamide, 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-, Celebrex, SC-58635, YM 177

    Given PO

  • CobimetinibDrug

    Also called Cotellic, GDC-0973, MEK Inhibitor GDC-0973, XL518

    Given PO

  • CopanlisibDrug

    Also called BAY 80-6946, PI3K Inhibitor BAY 80-6946

    Given IV

  • DabrafenibDrug

    Also called BRAF Inhibitor GSK2118436, GSK-2118436, GSK-2118436A, GSK2118436

    Given PO

  • DacomitinibDrug

    Also called EGFR Inhibitor PF-00299804, PF-00299804, PF-00299804-03, PF-299804

    Given PO

  • DarolutamideDrug

    Also called Antiandrogen ODM-201, BAY 1841788, BAY-1841788, BAY1841788

    Given PO

  • DasatinibDrug

    Also called BMS-354825, Dasatinib Hydrate, Dasatinib Monohydrate, Sprycel

    Given PO

  • DoxorubicinDrug

    Also called Adriablastin, Hydroxydaunomycin, Hydroxyl Daunorubicin, Hydroxyldaunorubicin

    Given IV

  • DurvalumabBiological

    Also called Imfinzi, Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI-4736, MEDI4736

    Given IV

  • EnasidenibDrug

    Also called AG-221, CC-90007 Free Base

    Given PO

  • EntrectinibDrug

    Also called Rozlytrek, RXDX 101, RXDX-101, RXDX101

    Given PO

  • EnzalutamideDrug

    Also called ASP9785, MDV3100, Xtandi

    Given PO

  • ErlotinibDrug

    Given PO

  • EverolimusDrug

    Also called 42-O-(2-Hydroxy)ethyl Rapamycin, Afinitor, Certican, RAD 001

    Given PO

  • FluorouracilDrug

    Also called 5 Fluorouracil, 5 Fluorouracilum, 5 FU, 5-Fluoro-2,4(1H, 3H)-pyrimidinedione

    Given IV

  • IdelalisibDrug

    Also called CAL-101, GS 1101, GS-1101, Phosphoinositide-3 Kinase Delta Inhibitor CAL-101

    Given PO

  • ImatinibDrug

    Given PO

  • IpilimumabBiological

    Also called Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, Ipilimumab Biosimilar CS1002, MDX-010

    Given IV

  • LenvatinibDrug

    Also called E7080, ER-203492-00, Multi-Kinase Inhibitor E7080

    Given PO

  • LeucovorinDrug

    Also called Folinic acid

    Given IV

  • LorlatinibDrug

    Also called 2H-4,8-Methenopyrazolo(4,3-H)(2,5,11)benzoxadiazacyclotetradecine-3-carbonitrile, 7-amino-12-fluoro-10,15,16,17-tetrahydro-2,10,16-trimethyl-15-oxo-, (10R)-, Lorbrena, PF-06463922

    Given PO

  • LosartanDrug

    Given PO

  • Nab-paclitaxelDrug

    Also called ABI 007, ABI-007, Abraxane, Albumin-bound Paclitaxel

    Given IV

  • NeratinibDrug

    Also called (2E)-N-(4-((3-chloro-4-((pyridin-2-yl)methoxy)phenyl)amino)-3-cyano-7-ethoxyquinolin-6-yl)-4-(dimethylamino)but-2-enamide, HKI 272, HKI-272, PB 272

    Given PO

  • NivolumabBiological

    Also called BMS-936558, CMAB819, MDX-1106, NIVO

    Given IV

  • OlaparibDrug

    Also called AZD 2281, AZD-2281, AZD2281, KU-0059436

    Given PO

  • OxaliplatinDrug

    Also called 1-OHP, Ai Heng, Aiheng, Dacotin

    Given IV

  • PalbociclibDrug

    Also called 6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-8h-pyrido(2,3-d)pyrimidin-7-one, Ibrance, PD 0332991, PD 332991

    Given PO

  • PanobinostatDrug

    Also called Faridak, LBH589

    Given PO

  • PembrolizumabBiological

    Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475

    Given IV

  • PertuzumabBiological

    Also called 2C4, 2C4 Antibody, HS627, MoAb 2C4

    Given IV

  • PonatinibDrug

    Also called AP-24534, AP24534

    Given PO

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

  • RegorafenibDrug

    Also called BAY 73-4506, REGORAFENIB ANHYDROUS, Stivarga

    Given PO

  • RuxolitinibDrug

    Also called INCB-18424, INCB18424, Jakafi, Oral JAK Inhibitor INCB18424

    Given PO

  • SirolimusDrug

    Also called AY 22989, RAPA, Rapamune, Rapamycin

    Given PO

  • SorafenibDrug

    Also called BA4 43 9006, BAY 43-9006, Bay-439006

    Given PO

  • SunitinibDrug

    Given PO

  • TrametinibDrug

    Also called GSK1120212, JTP-74057, MEK Inhibitor GSK1120212

    Given PO

  • Trastuzumab EmtansineBiological

    Also called Ado Trastuzumab Emtansine, ADO-Trastuzumab Emtansine, Kadcyla, PRO132365

    Given IV

  • TretinoinDrug

    Also called 2,4,6,8-Nonatetraenoic acid, 3, 7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-, (all-E)-, Aberel, Airol, Aknoten

    Given PO

  • VemurafenibDrug

    Also called BRAF (V600E) kinase inhibitor RO5185426, BRAF(V600E) Kinase Inhibitor RO5185426, PLX-4032, PLX4032

    Given PO

  • VenetoclaxDrug

    Also called ABT-0199, ABT-199, ABT199, GDC-0199

    Given PO

  • VismodegibDrug

    Also called Erivedge, GDC-0449, Hedgehog Antagonist GDC-0449

    Given PO

  • VorinostatDrug

    Also called L-001079038, MSK-390, SAHA, Suberanilohydroxamic Acid

    Given PO

Study groups in NCT03878524
Study groupRoleWhat they receive
Treatment (biospecimen collection, 2 drug combination)ExperimentalTUMOR BIOPSY: Patients undergo collection of tissue samples. Clinical analytics are performed on the samples and analyzed by a clinical tumor board to recommend a treatment option based on those analytics. SMMART-PRIME TREATMENT: Patients receive a combination of 2 drugs (Drug A and Drug B, selected from interventions below). Doses will be escalated within individual patients over time. As described in detail below, escalation will occur monthly and is anticipated to occur as follows: first month - 100% FDA approved dose Drug A + 25% FDA approved dose Drug B; second month -- 100% dose Drug A + 50% dose Drug B; third month -- 100% dose Drug A + 100% dose Drug B. All dose-escalations will be reviewed and approved by an independent consultant outside of Oregon Health \& Science University (OHSU). Treatment will continue for up to the end of 6 treatment cycles (cycle length is between 21-28 days) in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Abemaciclib; Drug: Abiraterone; Drug: Afatinib; Biological: Bevacizumab; Drug: Bicalutamide; Procedure: Biospecimen Collection; Drug: Bortezomib; Drug: Cabazitaxel; Drug: Cabozantinib; Drug: Capecitabine; Drug: Carboplatin; Drug: Celecoxib; Drug: Cobimetinib; Drug: Copanlisib; Drug: Dabrafenib; Drug: Dacomitinib; Drug: Darolutamide; Drug: Dasatinib; Drug: Doxorubicin; Biological: Durvalumab; Drug: Enasidenib; Drug: Entrectinib; Drug: Enzalutamide; Drug: Erlotinib; Drug: Everolimus; Drug: Fluorouracil; Drug: Idelalisib; Drug: Imatinib; Biological: Ipilimumab; Drug: Lenvatinib; Drug: Leucovorin; Drug: Lorlatinib; Drug: Losartan; Drug: Nab-paclitaxel; Drug: Neratinib; Biological: Nivolumab; Drug: Olaparib; Drug: Oxaliplatin; Drug: Palbociclib; Drug: Panobinostat; Biological: Pembrolizumab; Biological: Pertuzumab; Drug: Ponatinib; Other: Quality-of-Life Assessment; Drug: Regorafenib; Drug: Ruxolitinib; Drug: Sirolimus; Drug: Sorafenib; Drug: Sunitinib; Drug: Trametinib; Biological: Trastuzumab Emtansine; Drug: Tretinoin; Drug: Vemurafenib; Drug: Venetoclax; Drug: Vismodegib; Drug: Vorinostat

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Feasibility of implementing an individualized treatment strategy (number of participants to receive first dose)

    Measured as the number of participants to receive the first dose of Serial Measurements of Molecular and Architectural Responses to Therapy (SMMART)-PRIME therapy (Therapy #1) within 3 months from the date of Clinical Tumor Board providing a recommended drug combination.

    Measured: From date of tumor board recommendation to first dose of SMMART-PRIME Therapy #1 (up to 3 months)

Secondary outcomes (4)

  1. Incidence of grade 3+ toxicities attributable to assigned study drug(s)

    Measured with National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Criteria version 5.0.

    Measured: 30 days post completion of each SMMART-PRIME Therapy (up to 6 months)

  2. Time to treatment discontinuation

    Measured as time (days) from start of SMMART-PRIME Therapy #1 to discontinuation for any reason.

    Measured: Completion of SMMART-PRIME Therapy #1 (up to 6 months)

  3. Overall survival (OS)

    Overall survival (OS) is defined as the time (days) from start of SMMART-PRIME Therapy #1 to death from any reason.

    Measured: Death from any cause (up to 60 months after the last dose of SMMART-PRIME Therapy #1)

  4. Time to decline (TTD)

    Measured time (days) from start of SMMART-PRIME Therapy #1 to recorded Eastern Cooperative Oncology Group (ECOG) performance status >= 3 using cumulative incidence methods.

    Measured: Completion of SMMART-PRIME Therapy #1 (up to 6 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Mar 2019
  2. Study start1 Apr 2020
  3. Primary completion10 Dec 2020
  4. Study completion10 Dec 2020

Why it stopped: Low accrual

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
2 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03878524
Sponsor's protocol ID
STUDY00015588
Other IDs
NCI-2020-02743, STUDY00015588
Status last verified
Feb 2024
First submitted
14 Mar 2019
Last updated
4 Mar 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Tost J, Ak-Aksoy S, Campa D, Corradi C, Farinella R, Ibanez-Costa A, Dubrot J, Earl J, Melian EB, Kataki A, Kolnikova G, Madjarov G, Chaushevska M, Strnadel J, Tanic M, Tomas M, Dubovan P, Urbanova M, Buocikova V, Smolkova B. Leveraging epigenetic alterations in pancreatic ductal adenocarcinoma for clinical applications. Semin Cancer Biol. 2025 Feb;109:101-124. doi: 10.1016/j.semcancer.2025.01.003. Epub 2025 Jan 23.

    PubMed 39863139

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