SMMART Adaptive Clinical Treatment (ACT) Trial
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|ClinicalTrials.gov Identifier: NCT05238831|
Recruitment Status : Not yet recruiting
First Posted : February 14, 2022
Last Update Posted : July 14, 2022
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|Condition or disease||Intervention/treatment||Phase|
|Anatomic Stage III Breast Cancer AJCC v8 Anatomic Stage IV Breast Cancer AJCC v8 Locally Advanced Breast Carcinoma Locally Advanced Malignant Solid Neoplasm Locally Advanced Ovarian Carcinoma Metastatic Breast Carcinoma Metastatic Malignant Solid Neoplasm Metastatic Ovarian Carcinoma Refractory Breast Carcinoma Refractory Malignant Solid Neoplasm Refractory Ovarian Carcinoma Stage III Ovarian Cancer AJCC v8 Stage IV Ovarian Cancer AJCC v8 Unresectable Malignant Solid Neoplasm Unresectable Ovarian Carcinoma||Procedure: Biopsy Procedure: Biospecimen Collection Biological: Ado-Trastuzumab Emtansine Drug: Alectinib Biological: Atezolizumab Biological: Bevacizumab Drug: Cobimetinib Drug: Entrectinib Biological: Hyaluronidase-zzxf/Pertuzumab/Trastuzumab Drug: Vemurafenib Drug: Vismodegib Drug: Alpelisib Drug: Nab-paclitaxel Drug: Olaparib Drug: Capecitabine Drug: Irinotecan Drug: Carboplatin Drug: Paclitaxel Drug: Niraparib Drug: Anastrozole Drug: Letrozole Drug: Vinorelbine Drug: Palbociclib Drug: Fulvestrant Drug: Eribulin Other: Quality-of-Life Assessment||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||131 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Serial Measurements of Molecular and Architectural Responses to Therapy (SMMART) Trial: Adaptive Clinical Treatment (ACT)|
|Estimated Study Start Date :||December 1, 2022|
|Estimated Primary Completion Date :||March 31, 2026|
|Estimated Study Completion Date :||March 31, 2026|
Experimental: Treatment (SMMART-ACT)
PRE-SCREENING: Patients undergo a screening biopsy and blood collection to assess their tumor. Clinical assays may be used to provide an individualized treatment which may or may not include a SMMART-ACT treatment regimen.
SMMART-ACT TREATMENT: Prior to enrollment, patients must receive a recommendation of one or more SMMART-ACT treatment regimens based on the SMMART-CAP clinical assays. Treatment may be administered alone or as part of a combination. For specific treatment recommendations, a monotherapy lead-in may be considered for up to 4 weeks which proceeds to a combination therapy. After about 2 weeks of single agent, participants undergo an on-study tumor biopsy. All other patients have the option to undergo a repeat biopsy during treatment. Treatment cycles repeat every 21 to 28 days in the absence of disease progression or unacceptable toxicity. Cycles are based on the study agent(s). At disease progression, patients have the option to undergo an additional biopsy.
Undergo tissue biopsy
Procedure: Biospecimen Collection
Undergo collection of blood
Biological: Ado-Trastuzumab Emtansine
Given intravenously (IV)
Given orally (PO)
Given by injection
Other: Quality-of-Life Assessment
Other Name: Quality of Life Assessment
- Proportion of participants that achieve clinical benefit (CR, PR or SD) per RECIST 1.1 [ Time Frame: Day 1 of SMMART-ACT intervention #1 within 6 months after initiating SMMART-ACT intervention ]An exact 95% confidence interval will be provided. Reasons as to why the feasibility endpoint was not met, including factors such as disease progression and death of the participant, will be descriptively summarized.
- Incidence of treatment-emergent Adverse Events [ Time Frame: Day 1 of each SMMART-ACT therapy up to 30 days after last dose of each SMMART-ACT therapy ]Measured by Common Terminology Criteria for Adverse Events version 5.0.
- Progression free survival [ Time Frame: Day 1 of SMMART-ACT intervention #1 up to date of disease progression, or death from any cause, assessed up to 60-months after the last dose of SMMART-ACT therapy #1 ]Will be estimated using the Kaplan-Meier method.
- Overall survival [ Time Frame: Day 1 of SMMART-ACT intervention #1 to death from any cause, assessed up to 60 months after last dose of SMMART-ACT therapy #1 ]Will be censored on the last date a participant is known to be alive.
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- PRE-SCREENING: Participant must provide written informed consent before any study-specific procedures or interventions are performed.
- PRE-SCREENING: Participants >= 18 years old at time of informed consent.
PRE-SCREENING: Participants must have a histologically or cytologically-confirmed locally-advanced or metastatic solid tumor malignancy that has progressed as follows:
* Participants with a solid tumor malignancy that is metastatic, or locally-advanced and surgically unresectable, and have documented progression after receiving at least 1 line of approved prior therapy for their advanced or metastatic disease. If recurrence occurred within 6 months of completion (last dose) of adjuvant/neoadjuvant therapy, the adjuvant/neoadjuvant therapy would count as 1 line of therapy.
PRE-SCREENING: Participants must have measurable disease as follows:
* Participants with solid tumors must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1.
- Tumor lesions located in a previously irradiated area, or in an area subjected to other loco-regional therapy, are considered measurable if progression has been clearly demonstrated in the lesion.
- Non-measurable bone only disease may include any of the following: blastic bone lesions, lytic bone lesions without a measurable soft tissue component, or mixed lytic-blastic bone lesions without a measurable soft tissue component
PRE-SCREENING: Participants with a solid tumor must have a lesion meeting the above criteria also and must be amenable to biopsy procedures performed per institutional standards.
- An exception may be permitted if the participant is unable to undergo a biopsy or is found to have insufficient tissue, but has tissue available collected within the past 90 days for assessment using SMMART-CAP, and has not received more than 1 intervening treatment for their cancer during this 90 day interval time.
- Patients with prostate cancer who have no measurable disease may be considered eligible for study participation.
- PRE-SCREENING: Participants undergoing a biopsy during the pre-screening period are permitted to receive an intervening therapy per institutional standards
TREATMENT: Participants who are of childbearing potential must agree to use an adequate method(s) of contraception while receiving study drugs, and for the minimum required time after the last dose of study drug(s) as specified by the SMMART-ACT drug agents. Participants must also agree to refrain from donating, or retrieving for their own use, eggs during this period. Participants of childbearing potential are defined as those who are postmenarchal and do not meet one of the following criteria:
- Surgically sterile (they have undergone a total hysterectomy, bilateral tubal ligation, bilateral oophorectomy or bilateral salpingectomy)
- Postmenopausal. Participant is defined as postmenopausal if they have undergone bilateral oophorectomy, or are amenorrheic for at least 12 months without an alternative medical cause. If amenorrhea for 12 months is uncertain, then a high follicle-stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state
- TREATMENT: Sperm-producing participants must agree to use an adequate method(s) of contraception for the duration of receiving study drug(s) and for the minimum required time after the last dose of study drug(s), if required by the SMMART-ACT drug agent(s) and partner is of childbearing potential, unless participant is surgically sterile and no additional methods are required. Sperm-producing participants are considered surgically sterile if they are have undergone a vasectomy and have received medical confirmation of successful surgery.
- TREATMENT: Participants of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to start of study drug administration.
- TREATMENT: Participants must have received a treatment recommendation from their treating physician, or a medical review panel (e.g., multi-disciplinary tumor board, disease-site-specific tumor board, or molecular tumor board), based on the results of one or more clinical assays comprising the SMMART-CAP that matches one or more of the study - - - - TREATMENT: Any major surgery must have been completed >= 4 weeks prior to initiating assigned study intervention, and there is no anticipation of need for a major surgical procedure during the study
TREATMENT: Participants must have discontinued prior therapies for cancer, including specifically: chemotherapy, radiotherapy, or immunotherapy for at least 21 days for myelosuppressive agents or 14 days for non-myelosuppressive agents prior to initiating assigned study intervention. The following exceptions are permitted:
- Participants receiving a hormone therapy (e.g., selective estrogen modifiers [SERM], selective estrogen degraders [SERD], aromatase inhibitors [AI], luteinizing hormone-releasing hormone [LHRH] analogs) as part of the standard management of their disease may continue to receive their prescribed hormone therapy independent of their assigned study intervention.
- Participants receiving an androgen deprivation therapy (e.g., LHRH) or an androgen function inhibitor (e.g. enzalutamide) as part of the standard management of their disease may continue to receive their prescribed androgen deprivation therapy (ADT) or androgen function inhibitor independent of their assigned study intervention.
- TREATMENT: Participants must have Eastern Cooperative Oncology Group (ECOG) performance status =< 2 and a physician assessed life expectancy of >= 6 months
TREATMENT: Absolute neutrophil count (ANC) >= 1,500 / uL (1.5 K/cu mm) (on or by the time of starting study intervention)
* May be waived on a case-by-case basis for participant populations recognized to have normal baseline values below this level
- TREATMENT: Platelets >= 100,000 / uL (100 K/cu mm) (on or by the time of starting study intervention)
- TREATMENT: Hemoglobin >= 9 g/dL (or >= 5.6 mmol/L) (on or by the time of starting study intervention)
TREATMENT: 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/1.73m^2 for participants with creatinine levels > 1 x institutional ULN (on or by the time of starting study intervention)
* 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
- TREATMENT: Total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for participants with total bilirubin levels > 1.5 x ULN (on or by the time of starting study intervention)
- TREATMENT: Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x ULN (on or by the time of starting study intervention)
- 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 (on or by the time of starting study intervention)
- 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 (on or by the time of starting study intervention)
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)
TREATMENT: Participants must have had all toxicities due to prior therapy resolved to baseline or at least grade 1 (per Common Terminology Criteria for Adverse Events [CTCAE] v5.0) before administration of study intervention. The following exceptions are permitted:
- Exceptions to recovery from acute effects of a prior therapy include: alopecia, fatigue, and lymphopenia.
- Participants with toxicities attributed to prior anti-cancer therapy that are not expected to resolve and result in long lasting sequelae, such as neuropathy after platinum-based therapy, are permitted to enroll.
- 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.
- TREATMENT: Participants must meet the study intervention-specific eligibility criteria for the intended recommended therapy
- OVARIAN CANCER: In general, participants who have malignancies for which there is a standard of care that can confer overall survival (OS), disease-free survival (DFS) or progression-free survival (PFS) improvement should be excluded. If there is reason that a standard of care option is not amendable to the participant disease management for reasons such as known contraindications, then patients may be considered eligible for participation.
- BREAST CANCER: In general, participants who have malignancies for which there is a standard of care that can confer OS, DFS or PFS improvement should be excluded. If there is reason that a standard of care option is not amendable to the participant disease management for reasons such as known contraindications, then patients may be considered eligible for participation.
- PRE-SCREENING: 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.
PRE-SCREENING: Prisoners or participants who are involuntarily incarcerated
* Participants who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness are not eligible
TREATMENT: Participants may not have untreated brain or central nervous system (CNS) metastases or brain/CNS metastases that has progressed (e.g., evidence of new or enlarging brain metastasis or new neurological symptoms attributable to brain/CNS metastases). A scan to confirm absence of brain metastasis is not required
- Participants must be at least 14 days between last day of stereotactic radiosurgery or gamma-knife treatment and day 1 start of assigned study therapy, or
- At least 28 days between last day of whole brain radiation therapy and day 1 start of assigned study therapy, or
- At least 14 days since last dose of corticosteroids (> 10 mg/day prednisone equivalents) and day 1 start of assigned study therapy
- TREATMENT: Participants cannot be on other forms of anti-cancer therapy at the same time, except as described within this protocol.
TREATMENT: Participant has had more than 1 intervening therapy for treatment of their cancer since the time of the pre-screening biopsy.
* Note: Participants who have a pre-screening biopsy while receiving a standard of care 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 1 line of intervening therapy.
TREATMENT: Participant is seropositive with human immunodeficiency virus (HIV) or has active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV) with the following exceptions:
- HIV-infected participants on stable (>= 4 weeks) anti-retroviral therapy with undetectable viral load within out any history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection within 12 months and a CD4+ T-cell count >= 350 cells/uL are eligible for this trial provided that there is minimal interactions or overlapping toxicity of the antiretroviral therapy with their study intervention.
- In cases, where the study intervention has known CYP3A/4 interactions, protease inhibitor therapy is prohibited. Participants may remain eligible if alternative replacements to protease inhibitors can be made (e.g., dolutegravir given with tenofovir/emtricitabine; raltegravir given with tenofovir and emtricitabine).
- Active HBV infection is defined as having a positive hepatitis B surface antigen test. Participants with past HBV infection or resolved HBV infection (defined as the presence of hepatitis B core antibody [HBcAb] and absence of HBsAg) are eligible only if they are negative for HBV deoxyribonucleic acid (DNA)
- Patients who are HCV Ab positive but HCV ribonucleic acid (RNA) negative due to prior treatment or natural resolution are eligible
- Patients with untreated HCV may be enrolled if the HCV is stable, the patient is not at risk for hepatic decompensation, and the intended treatment is not expected to exacerbate the HCV infection
- Patients on concurrent HCV treatment may be enrolled if they have HCV below the limit of quantification
TREATMENT: Participants with any uncontrolled intercurrent illness that may interfere with planned treatment including, but not limited to:
- Symptomatic congestive heart failure (New York Heart Association [NYHA] class III or IV)
- Unstable angina pectoris or coronary angioplasty, or stenting within 6 months prior to enrollment,
- Cardiac arrhythmia (ongoing cardiac dysrhythmias of grade >=2 [per National Cancer Institute (NCI) CTCAE v5.0]),
- Intra-cardia defibrillators,
- Known cardiac metastases,
- History of abnormal cardiac valve morphology (>= grade 2),
- Chronic graft versus host disease (GVHD) or on immunosuppressive therapy for the control of GVHD,
- Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia.
- TREATMENT: Inability or unwillingness to take oral medication (only for assigned study interventions that include an oral study agent).
- TREATMENT: Participants with history of allergy to a study agent or its excipients that is part of the assigned study intervention.
- TREATMENT: Participants that are pregnant or breast-feeding. Participants must also agree 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.
- TREATMENT: Participants with any condition that, in the opinion of the investigator, could jeopardize the participant's safety or adherence to the study protocol.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05238831
|Contact: Lara Davis, M.D.||firstname.lastname@example.org|
|United States, Oregon|
|OHSU Knight Cancer Institute|
|Portland, Oregon, United States, 97239|
|Contact: Lara Davis, M.D. 503-494-6594 email@example.com|
|Principal Investigator: Lara Davis, M.D.|
|Principal Investigator:||Lara Davis, M.D.||OHSU Knight Cancer Institute|
|Responsible Party:||Lara Davis, Principal Investigator, OHSU Knight Cancer Institute|
|Other Study ID Numbers:||
NCI-2021-12938 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
|First Posted:||February 14, 2022 Key Record Dates|
|Last Update Posted:||July 14, 2022|
|Last Verified:||July 2022|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Carcinoma, Ovarian Epithelial
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms by Site
Endocrine Gland Neoplasms
Genital Neoplasms, Female
Endocrine System Diseases