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Advanced Breast CarcinomaEarly Phase 1NCT05238831

SMMART Adaptive Clinical Treatment (ACT) Trial

A Early Phase 1 study testing Alectinib, Alpelisib and Anastrozole in people with Advanced Breast Carcinoma and Advanced Malignant Solid Neoplasm, run by OHSU Knight Cancer Institute.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record

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Trial summary

SMMART-ACT is a feasibility pilot study to determine if testing samples from a participant's cancer using a precision medicine approach can be used to identify specific drugs or drug combinations that can help control their disease. The safety and tolerability of the drug or drug combination is also to be studied. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Alectinib, Alpelisib and Anastrozole
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
30 Jan 2023to 31 May 2026
Phase
Early 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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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 version 1.1 (RECIST v1.1) 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 successful SMMART-CAP tumor tissue sample collected within the last 90 days may be eligible, given that =<1 treatment has been received within =< 90 days of that biopsy.
  • PRE-SCREENING: Eastern Cooperative Oncology Group (ECOG) performance status of =< 2.
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  • PRE-SCREENING: Physician assessed life expectancy of >= 6 months.
  • 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 treatment recommendation of at least one per protocol ACT intervention 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)
  • May be waived, per principal investigator (PI), on a case-by-case basis for participant populations recognized to have normal baseline values below this level
  • 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 =< 1.5 x institutional upper limit of normal (IULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) >= 50 mL/min/1.73m^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.
  • PRIMARY TREATMENT: Total bilirubin =< 1.5 x IULN OR direct bilirubin IULN for individuals with total bilirubin levels > 1.5 x IULN. (assessed at primary [post pre-screening] screening, or by the time that study intervention commences)
  • PRIMARY TREATMENT: Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) / alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x IULN. (assessed at primary [post pre-screening] screening, or by the time that study intervention commences)
  • PRIMARY TREATMENT: International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x upper limit of normal (ULN) unless individual is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within intended therapeutic range of intended anticoagulant therapy. (assessed at primary [post pre-screening] screening, or by the time that study intervention commences)
  • PRIMARY 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 anticoagulant therapy. (assessed at primary [post pre-screening] screening, or by the time that study intervention commences)
  • PRIMARY TREATMENT: Body mass index (BMI) >16.0 and < 35.0 kg/m^2
  • 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)
  • PRIMARY TREATMENT: Toxicities due to prior therapies should be resolved to baseline or grade 1 (per Common Terminology Criteria for Adverse Events [CTCAE] v5.0) before administration of study intervention. The following exceptions are permitted:
  • Alopecia, fatigue, and lymphopenia due to prior therapies.
  • Toxicities attributed to prior anti-cancer therapy that are not expected to resolve and to result in long lasting sequelae, (e.g., neuropathy after platinum-based therapy), may be permitted.
  • PRIMARY TREATMENT: Palliative radiation therapy completed >= two weeks prior to start of SMMART-ACT treatment to a measurable disease lesion (s).
  • PRIMARY TREATMENT: Additional eligibility criteria for the intended recommended therapy must also be met.
  • PRIMARY TREATMENT: Study intervention-specific eligibility criteria for the intended, recommended therapy must also be met.
  • CANCER SPECIFIC BREAST CANCER: Lesion(s) remain measurable after systemic therapies, as follows:
  • At least one prior line of pharmacological therapy for hormone receptor (HR) positive, human epidermal growth factor receptor 2 (HER2)-negative disease.
  • At least one prior line of targeted therapy for HER2-postive disease.
  • At least one prior line of combination therapy for triple negative disease lacking a BRCA1/2 mutation.
  • At least one prior line of therapy with a PARP inhibitor for triple negative disease with a BRCA1/2 mutation.

Who cannot join

  • PRE-SCREENING: Evidence of active malignancy of another cancer with a natural 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 non-melanomatous skin cancer.
  • PRE-SCREENING: Involuntarily incarceration, including, but not limited to, imprisonment and compulsory detained for treatment of psychiatric or physical (e.g., infectious disease) illness.
  • PRIMARY TREATMENT: Any brain/central nervous system (CNS) metastases or brain/CNS metastases that has progressed (e.g., evidence of new or enlarging brain metastasis that progresses within =< four weeks of CNS directed treatment as ascertained by clinical examination(s) and magnetic resonance imaging (MRI) or computed tomography (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 may 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: Untreated and/or uncured hepatitis C virus (HCV) infection, as evidenced by detectable hepatitis B virus (HBC) ribonucleic acid (RNA) by polymerase chain reaction (PCR). Prior treatment, concurrent treatment, and natural resolution of HCV infection are not exclusionary given (1) no risk for hepatic decompensation and (2) the intended SMMART ACT treatment is not expected to exacerbate HCV infection.
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  • 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 v5.0]),
  • 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.
  • PRIMARY TREATMENT: Severe infection within < four weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia.
  • PRIMARY TREATMENT: Inability or unwillingness to take oral medication (only for assigned oral study interventions).
  • PRIMARY TREATMENT: History of allergy to an assigned study agent or its excipients.
  • PRIMARY TREATMENT: Current pregnancy, currently breast-feeding, or unwillingness to not breastfeed while receiving study drug(s) or for the minimum required time after the last dose of study drug(s) as specified by the SMMART-ACT drug agents.
  • PRIMARY TREATMENT: Any condition that, in the opinion of the investigator, could jeopardize the participant's safety or adherence to the study protocol.

About this study

Official title: Serial Measurements of Molecular and Architectural Responses to Therapy (SMMART) Trial: Adaptive Clinical Treatment (ACT)

SMMART-ACT is a feasibility pilot study to determine if testing samples from a participant's cancer using a precision medicine approach can be used to identify specific drugs or drug combinations that can help control their disease. The safety and tolerability of the drug or drug combination is also to be studied. Another purpose is for researchers to study tumor cells to try to learn why some people respond to a certain therapy and others do not, and why some cancer drugs stop working. The study population will include participants with advanced breast, ovarian, prostate, or pancreatic malignancies, or sarcomas.

Read the detailed description

PRIMARY OBJECTIVE:

  1. Feasibility of utilizing a SMMART-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:

  1. Safety and tolerability of assigned ACT intervention per cancer type; II. Preliminary indications of efficacy based on disease-specific responses; and.

III. Estimated survival benefit per cancer type.

EXPLORATORY OBJECTIVES:

  1. Durability of a 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:

PRE-SCREENING: Participants undergo a screening biopsy and blood collection for review and assessment of their tumor, utilizing one or more of the SMMART-Clinical Analytics Platform (SMMART-CAP) assays. The clinical assays may be used to provide an optimal and individualized treatment approach which may or may not include a SMMART-ACT treatment regimen.

SMMART-ACT TREATMENT: Prior to enrollment, participants must receive a treatment recommendation, via a SMMART-ACT Tumor Board, that consists of one or more of the pre-defined SMMART-ACT treatment regimen options. Participants are considered enrolled in SMMART-ACT if they receive a targeted SMMART-ACT treatment regimen, which may be administered in monotherapy or in combination with other targeted agents or immunotherapies, chemotherapies, or radiation. A combination treatment plan may include a two-week monotherapy lead-in, followed by a combination treatment regimen. Regardless of overall recommended treatment plan details, each SMMART-ACT study intervention must have an established RP2D that was determined in a prior clinical trial. All participants are required to undergo an On-Treatment Biopsy after two weeks on the first dose of study drug(s), and before starting Cycle 2, regardless of whether the participant is on a monotherapy, monotherapy-induction or combination regimen. Participants will continue to receive the study agent(s) after their On-Treatment Biopsy according to the biopsy results and the results of ongoing safety and clinical assessments. Treatment cycles repeat every 21 to 28 days in the absence of disease progression or unacceptable toxicity. Cycles are determined based on the study agent(s). Upon disease progression, participants are given the option to undergo an additional repeat biopsy.

Participants completing study treatment due to disease progression are followed every 3 months for 1 year, then every 6 months for 5 years. Participants completing study treatment without disease progression are followed every 6-12 weeks for up to 5 years or until disease progression, start of a new therapy, withdrawal from the study, or death, whichever occurs first.

Being tested
Alectinib, Alpelisib, Anastrozole, Atezolizumab, Bevacizumab
Medical subject headings
Sarcoma, Breast Neoplasms, Ovarian Neoplasms, Prostatic Neoplasms, Pancreatic Neoplasms

What participants receive

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

  • AlectinibDrug

    Also called AF-802, AF802, Alecensa, ALK Inhibitor RO5424802

    Given orally (PO)

  • AlpelisibDrug

    Also called BYL719, Phosphoinositide 3-kinase Inhibitor BYL719, Piqray, VIJOICE

    Given PO

  • AnastrozoleDrug

    Also called Anastrazole, Arimidex, ICI D1033, ICI-D1033

    Given PO

  • AtezolizumabBiological

    Also called MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A

    Given IV

  • BevacizumabBiological

    Also called ABP 215, Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF Monoclonal Antibody SIBP04

    Given IV

  • BiopsyProcedure or surgery

    Also called BIOPSY_TYPE, Bx

    Undergo tissue biopsy

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo collection of blood

  • CapecitabineDrug

    Also called Ro 09-1978/000, Xeloda

    Given PO

  • CarboplatinDrug

    Also called Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino

    Given IV

  • CobimetinibDrug

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

    Given PO

  • EntrectinibDrug

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

    Given PO

  • EribulinDrug

    Also called ER-086526

    Given IV

  • FulvestrantDrug

    Also called Faslodex, Faslodex(ICI 182,780), ICI 182,780, ICI 182780

    Given by injection

  • Hyaluronidase-zzxf/Pertuzumab/TrastuzumabBiological

    Also called Pertuzumab, Trastuzumab, and Hyaluronidase-zzxf, Pertuzumab/Trastuzumab/Hyaluronidase-zzxf, Phesgo

    Given phesgo SC

  • IrinotecanDrug

    Given IV

  • LetrozoleDrug

    Also called CGS 20267, Femara

    Given PO

  • Nab-paclitaxelDrug

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

    Given IV

  • NiraparibDrug

    Also called MK-4827, MK4827

    Given PO

  • OlaparibDrug

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

    Given PO

  • PaclitaxelDrug

    Also called Anzatax, Asotax, Bristaxol, Praxel

    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 IV

  • PertuzumabBiological

    Also called 2C4, 2C4 Antibody, EG1206A, HLX11

    Given subcutaneously (SC)

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

  • TrastuzumabBiological

    Also called ABP 980, ALT02, Anti-c-ERB-2, Anti-c-erbB2 Monoclonal Antibody

    Given SC

  • Trastuzumab EmtansineBiological

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

    Given intravenously (IV)

  • VemurafenibDrug

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

    Given PO

  • VinorelbineDrug

    Also called Dihydroxydeoxynorvinkaleukoblastine

    Given IV

  • VismodegibDrug

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

    Given PO

Study groups in NCT05238831
Study groupRoleWhat they receive
Treatment (SMMART-ACT)ExperimentalAdministered in monotherapy or in combination with other targeted agents or immunotherapies, chemotherapies, or radiation. Combination treatment plans may include a two-week monotherapy lead-in, followed by a combination treatment regimen. Each ACT study intervention must have an established RP2D determined in a prior clinical trial. Participants undergo a Pre-Treatment Biopsy, plus an On-Treatment Biopsy after two weeks on first dose of study drug(s) and prior to starting Cycle 2, regardless of regimen. Participants continue to receive study agent(s) after the On-Treatment Biopsy, according to the biopsy results and the results of ongoing safety and clinical assessments. Treatment cycles repeat every 21 to 28 days in the absence of disease progression or unacceptable toxicity. Cycles are determined based on the study agent(s). Upon disease progression, participants are given the option to undergo an additional biopsy.
Receives: Drug: Alectinib; Drug: Alpelisib; Drug: Anastrozole; Biological: Atezolizumab; Biological: Bevacizumab; Procedure: Biopsy; Procedure: Biospecimen Collection; Drug: Capecitabine; Drug: Carboplatin; Drug: Cobimetinib; Drug: Entrectinib; Drug: Eribulin; Drug: Fulvestrant; Biological: Hyaluronidase-zzxf/Pertuzumab/Trastuzumab; Drug: Irinotecan; Drug: Letrozole; Drug: Nab-paclitaxel; Drug: Niraparib; Drug: Olaparib; Drug: Paclitaxel; Drug: Palbociclib; Biological: Pertuzumab; Other: Quality-of-Life Assessment; Biological: Trastuzumab; Biological: Trastuzumab Emtansine; Drug: Vemurafenib; Drug: Vinorelbine; Drug: Vismodegib

What is being measured

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

  1. Proportion of participants who receive an ACT therapy based an ACT Tumor Board recommendation.

    At interim analysis, if greater than or equal to 11 of the first 15 enrolled participants (80%) receive C1D1 of the recommended ACT drug regimen, the feasibility threshold will be met. If not attained, reasons as to why the feasibility endpoint was not met will be reviewed.

    Measured: From time of SMMART-ACT Tumor Board review to first dose of SMMART-ACT study drug regime as evaluated at interim analysis (approximately 2 years)

Secondary outcomes (6)

  1. Incidence of treatment-emergent adverse events

    Measured by Common Terminology Criteria for Adverse Events version 5.0.

    Measured: First dose of study drug up to 30 days after last dose study drug(s)

  2. Rate of treatment discontinuation due to toxicities and/or intolerability.

    Measured by Common Terminology Criteria for Adverse Events version 5.0.

    Measured: First dose of study drug to last dose study drug(s)

  3. Overall response rate (ORR)

    Will be assessed by ORR = complete response (CR)+ partial response (PR) per Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 or in accordance with definition for pseudoprogression indications for immuno monotherapy regimens. Will be estimated using the Kaplan-Meier method.

    Measured: At 6 months from cycle 1 day 1 +/- 2 weeks (each cycle may be 21 or 28 days, depending on the assigned SMMART ACT regimen)

  4. Progression free survival

    Will be censored at the date of last adequate assessment visit and will be estimated using the Kaplan Meier method.

    Measured: From the first dose of study drug until the earliest date of disease progression, as measured by investigator assessment, or death due to any cause (until the end of long-term follow-up (LTFU)), LTFU is up to 5 years

  5. Disease-specific survival

    Will be estimated using cumulative incidence methods.

    Measured: Time from the first day of treatment with study intervention to death as a result of the disease at time of last follow-up, LTFU is up to five years from time of last dose of study therapy

  6. Overall survival

    Will be censored on the last date a participant is known to be alive and will summarized descriptively using the Kaplan-Meier method. The median and 95% confidence interval, will be included in the estimations, if possible.

    Measured: From the time of first dose of study drug until death from any cause (until the end of long-term follow-up), LTFU is up to 5 years

Timeline

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

  1. First posted14 Feb 2022
  2. Study start30 Jan 2023 (estimated)
  3. Primary completion31 May 2026 (estimated)
  4. Study completion31 May 2026 (estimated)

Why it stopped: Withdrawn due to a change in therapeutic interventions.

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
Early Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05238831
Sponsor's protocol ID
STUDY00020679
Other IDs
NCI-2021-12938, STUDY00020679
Status last verified
Jan 2024
First submitted
9 Feb 2022
Last updated
23 Jan 2024
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No

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