Trial Title:
A Precision Medicine Approach (SMMART-ACT) for the Treatment of Patients With Advanced, Recurrent Sarcoma, Prostate, Breast, Ovarian or Pancreatic Cancer
NCT ID:
NCT06630325
Condition:
Advanced Breast Carcinoma
Advanced Malignant Solid Neoplasm
Advanced Ovarian Carcinoma
Advanced Pancreatic Carcinoma
Advanced Prostate Carcinoma
Advanced Sarcoma
Anatomic Stage III Breast Cancer AJCC v8
Anatomic Stage IV Breast Cancer AJCC v8
Recurrent Breast Carcinoma
Recurrent Ovarian Carcinoma
Recurrent Pancreatic Carcinoma
Recurrent Prostate Carcinoma
Recurrent Sarcoma
Stage III Ovarian Cancer AJCC v8
Stage III Pancreatic Cancer AJCC v8
Stage III Prostate Cancer AJCC v8
Stage IV Ovarian Cancer AJCC v8
Stage IV Pancreatic Cancer AJCC v8
Stage IV Prostate Cancer AJCC v8
Conditions: Official terms:
Carcinoma
Breast Neoplasms
Prostatic Neoplasms
Pancreatic Neoplasms
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Sarcoma
Recurrence
Tamoxifen
Paclitaxel
Carboplatin
Gemcitabine
Doxorubicin
Liposomal doxorubicin
Pemetrexed
Albumin-Bound Paclitaxel
Temozolomide
Letrozole
Fulvestrant
Olaparib
Gefitinib
Exemestane
Osimertinib
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Abemaciclib
Description:
Given PO
Arm group label:
Arm I (abemaciclib, gemcitabine)
Arm group label:
Arm II (abemaciclib, pemetrexed)
Arm group label:
Arm III (abemaciclib)
Arm group label:
Arm IV (abemaciclib, exemestane)
Arm group label:
Arm V (abemaciclib, letrozole)
Arm group label:
Arm VI (abemaciclib, tamoxifen)
Other name:
LY 2835219
Other name:
LY-2835219
Other name:
LY2835219
Other name:
Verzenio
Intervention type:
Procedure
Intervention name:
Biopsy
Description:
Undergo tumor biopsy
Arm group label:
Arm I (abemaciclib, gemcitabine)
Arm group label:
Arm II (abemaciclib, pemetrexed)
Arm group label:
Arm III (abemaciclib)
Arm group label:
Arm IV (abemaciclib, exemestane)
Arm group label:
Arm IX (fulvestrant)
Arm group label:
Arm V (abemaciclib, letrozole)
Arm group label:
Arm VI (abemaciclib, tamoxifen)
Arm group label:
Arm VII (gefitinib, pemetrexed, carboplatin)
Arm group label:
Arm VIII (olaparib, temozolomide)
Arm group label:
Arm X (gefitinib)
Arm group label:
Arm XI (olaparib)
Arm group label:
Arm XII (olaparib, carboplatin, paclitaxel)
Arm group label:
Arm XIII (olaparib, liposomal doxorubicin)
Arm group label:
Arm XIV (osimertinib)
Other name:
BIOPSY_TYPE
Other name:
Bx
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Arm I (abemaciclib, gemcitabine)
Arm group label:
Arm II (abemaciclib, pemetrexed)
Arm group label:
Arm III (abemaciclib)
Arm group label:
Arm IV (abemaciclib, exemestane)
Arm group label:
Arm IX (fulvestrant)
Arm group label:
Arm V (abemaciclib, letrozole)
Arm group label:
Arm VI (abemaciclib, tamoxifen)
Arm group label:
Arm VII (gefitinib, pemetrexed, carboplatin)
Arm group label:
Arm VIII (olaparib, temozolomide)
Arm group label:
Arm X (gefitinib)
Arm group label:
Arm XI (olaparib)
Arm group label:
Arm XII (olaparib, carboplatin, paclitaxel)
Arm group label:
Arm XIII (olaparib, liposomal doxorubicin)
Arm group label:
Arm XIV (osimertinib)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Drug
Intervention name:
Carboplatin
Description:
Given IV
Arm group label:
Arm VII (gefitinib, pemetrexed, carboplatin)
Arm group label:
Arm XII (olaparib, carboplatin, paclitaxel)
Other name:
Blastocarb
Other name:
Carboplat
Other name:
Carboplatin Hexal
Other name:
Carboplatino
Other name:
Carboplatinum
Other name:
Carbosin
Other name:
Carbosol
Other name:
Carbotec
Other name:
CBDCA
Other name:
Displata
Other name:
Ercar
Other name:
JM-8
Other name:
JM8
Other name:
Nealorin
Other name:
Novoplatinum
Other name:
Paraplatin
Other name:
Paraplatin AQ
Other name:
Paraplatine
Other name:
Platinwas
Other name:
Ribocarbo
Intervention type:
Procedure
Intervention name:
Echocardiography
Description:
Undergo echocardiography
Arm group label:
Arm XIII (olaparib, liposomal doxorubicin)
Arm group label:
Arm XIV (osimertinib)
Other name:
EC
Intervention type:
Drug
Intervention name:
Exemestane
Description:
Given PO
Arm group label:
Arm IV (abemaciclib, exemestane)
Other name:
Aromasin
Other name:
FCE-24304
Intervention type:
Drug
Intervention name:
Fulvestrant
Description:
Given IM
Arm group label:
Arm IX (fulvestrant)
Other name:
Faslodex
Other name:
Faslodex(ICI 182,780)
Other name:
ICI 182,780
Other name:
ICI 182780
Other name:
ICI-182780
Other name:
ICI182780
Other name:
ZD 9238
Other name:
ZD-9238
Other name:
ZD9238
Intervention type:
Drug
Intervention name:
Gefitinib
Description:
Given PO
Arm group label:
Arm VII (gefitinib, pemetrexed, carboplatin)
Arm group label:
Arm X (gefitinib)
Other name:
Iressa
Other name:
ZD 1839
Other name:
ZD-1839
Other name:
ZD1839
Intervention type:
Drug
Intervention name:
Gemcitabine
Description:
Given IV
Arm group label:
Arm I (abemaciclib, gemcitabine)
Other name:
dFdC
Other name:
dFdCyd
Other name:
Difluorodeoxycytidine
Intervention type:
Drug
Intervention name:
Letrozole
Description:
Given PO
Arm group label:
Arm V (abemaciclib, letrozole)
Other name:
CGS 20267
Other name:
CGS-20267
Other name:
CGS20267
Other name:
Femara
Other name:
Fempro
Intervention type:
Procedure
Intervention name:
Multigated Acquisition Scan
Description:
Undergo MUGA
Arm group label:
Arm XIII (olaparib, liposomal doxorubicin)
Arm group label:
Arm XIV (osimertinib)
Other name:
Blood Pool Scan
Other name:
Equilibrium Radionuclide Angiography
Other name:
Gated Blood Pool Imaging
Other name:
Gated Heart Pool Scan
Other name:
MUGA
Other name:
MUGA Scan
Other name:
Multi-Gated Acquisition Scan
Other name:
Radionuclide Ventriculogram Scan
Other name:
Radionuclide Ventriculography
Other name:
RNVG
Other name:
SYMA Scanning
Other name:
Synchronized Multigated Acquisition Scanning
Intervention type:
Drug
Intervention name:
Olaparib
Description:
Given PO
Arm group label:
Arm VIII (olaparib, temozolomide)
Arm group label:
Arm XI (olaparib)
Arm group label:
Arm XII (olaparib, carboplatin, paclitaxel)
Arm group label:
Arm XIII (olaparib, liposomal doxorubicin)
Other name:
AZD 2281
Other name:
AZD-2281
Other name:
AZD2281
Other name:
KU 0059436
Other name:
KU-0059436
Other name:
KU0059436
Other name:
Lynparza
Other name:
Olanib
Other name:
Olaparix
Other name:
PARP Inhibitor AZD2281
Intervention type:
Drug
Intervention name:
Osimertinib
Description:
Given PO
Arm group label:
Arm XIV (osimertinib)
Other name:
AZD 9291
Other name:
AZD-9291
Other name:
AZD9291
Other name:
Mereletinib
Intervention type:
Drug
Intervention name:
Paclitaxel
Description:
Given IV
Arm group label:
Arm XII (olaparib, carboplatin, paclitaxel)
Other name:
Anzatax
Other name:
Asotax
Other name:
Bristaxol
Other name:
Praxel
Other name:
Taxol
Other name:
Taxol Konzentrat
Intervention type:
Drug
Intervention name:
Pegylated Liposomal Doxorubicin Hydrochloride
Description:
Given IV
Arm group label:
Arm XIII (olaparib, liposomal doxorubicin)
Other name:
ATI-0918
Other name:
Caelyx
Other name:
Dox-SL
Other name:
Doxil
Other name:
Doxilen
Other name:
Doxorubicin HCl Liposomal
Other name:
Doxorubicin HCl Liposome
Other name:
Doxorubicin Hydrochloride Liposome
Other name:
Duomeisu
Other name:
Evacet
Other name:
LipoDox
Other name:
Lipodox 50
Other name:
Liposomal Adriamycin
Other name:
Liposomal Doxorubicin Hydrochloride
Other name:
Liposomal-Encapsulated Doxorubicin
Other name:
Pegylated Doxorubicin HCl Liposome
Other name:
Pegylated Liposomal Doxorubicin
Other name:
S-Liposomal Doxorubicin
Other name:
Stealth Liposomal Doxorubicin
Other name:
TLC D-99
Intervention type:
Drug
Intervention name:
Pemetrexed
Description:
Given IV
Arm group label:
Arm II (abemaciclib, pemetrexed)
Arm group label:
Arm VII (gefitinib, pemetrexed, carboplatin)
Other name:
MTA
Other name:
Multitargeted Antifolate
Other name:
Pemfexy
Intervention type:
Other
Intervention name:
Survey Administration
Description:
Ancillary studies
Arm group label:
Arm I (abemaciclib, gemcitabine)
Arm group label:
Arm II (abemaciclib, pemetrexed)
Arm group label:
Arm III (abemaciclib)
Arm group label:
Arm IV (abemaciclib, exemestane)
Arm group label:
Arm IX (fulvestrant)
Arm group label:
Arm V (abemaciclib, letrozole)
Arm group label:
Arm VI (abemaciclib, tamoxifen)
Arm group label:
Arm VII (gefitinib, pemetrexed, carboplatin)
Arm group label:
Arm VIII (olaparib, temozolomide)
Arm group label:
Arm X (gefitinib)
Arm group label:
Arm XI (olaparib)
Arm group label:
Arm XII (olaparib, carboplatin, paclitaxel)
Arm group label:
Arm XIII (olaparib, liposomal doxorubicin)
Arm group label:
Arm XIV (osimertinib)
Intervention type:
Drug
Intervention name:
Tamoxifen
Description:
Given PO
Arm group label:
Arm VI (abemaciclib, tamoxifen)
Other name:
TMX
Intervention type:
Drug
Intervention name:
Temozolomide
Description:
Given PO
Arm group label:
Arm VIII (olaparib, temozolomide)
Other name:
CCRG-81045
Other name:
Gliotem
Other name:
Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-
Other name:
M & B 39831
Other name:
M and B 39831
Other name:
Methazolastone
Other name:
RP-46161
Other name:
SCH 52365
Other name:
Temcad
Other name:
Temizole
Other name:
Temodal
Other name:
Temodar
Other name:
Temomedac
Other name:
TMZ
Summary:
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:
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
After completion of study treatment, patients are followed up 30 days, every 3 months for
1 year then every 6 months until year 5.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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 (RECIST) version
(v) 1.1 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 tumor tissue sample with successful SMMART-Clinical
Analytics Platform (CAP) assays, collected within the last 90 days, may be
eligible, so long as ≤ 1 treatment has been received within ≤ 90 days of that
biopsy
- PRE-SCREENING: Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
- PRE-SCREENING: Physician-assessed life expectancy of ≥ 6 months
- PRE-SCREENING: Additional eligibility criteria specific to their disease must also
be met
- 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 recommendation of at least one SMMART-ACT
therapy regimen defined within this protocol, 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)
- 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 OR measured or calculated creatinine clearance
(glomerular filtration rate [GFR] can also be used in place of creatinine or
creatinine clearance [CrCl]) ≤ 1.5 x institutional upper limit of normal (ULN)
(institutional upper limit of normal [IULN]) OR ≥ 50 mL/min/1.73 m^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.
- Creatinine clearance of > 30 mL/min may be considered given that renal toxicity
is not at increased risk and excretion is not major route of clearance for any
chosen SMMART-ACT therapeutic
- 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 glutamic pyruvic
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 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 (assessed at
primary [post pre-screening] screening, or by the time that study intervention
commences)
- 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] version [v]
5.0) 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: Study intervention-specific eligibility criteria for the
intended, recommended therapy must also be met
- CANCER-SPECIFIC CRITERIA (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-positive 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
Exclusion Criteria:
- PRE-SCREENING: Evidence of active malignancy of another cancer with a natural
history 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 nonmelanomatous
skin cancer
- PRE-SCREENING: Absence of biopsiable lesion, AND unavailable/insufficient archival
tissue
- PRIMARY TREATMENT: Any brain/central nervous system (CNS) metastasis that progresses
within ≤ four weeks of CNS directed treatment as ascertained by clinical
examination(s) and MRI or 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 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: More than one intervening line of therapy for treatment of their
cancer since the time of the pre-screening biopsy, exclusive of most maintenance
hormone therapies
- Note: Participants who have a pre-screening biopsy while receiving a standard
of care (SOC) 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 one line of intervening therapy
- PRIMARY TREATMENT: Untreated and/or uncured hepatitis C virus (HCV) infection, as
evidenced by detectable hepatitis B core (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
- 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 v 5.0]),
- 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
therapy, 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, current breastfeeding, 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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
OHSU Knight Cancer Institute-Northwest Portland
Address:
City:
Portland
Zip:
97210
Country:
United States
Contact:
Last name:
Lara E. Davis
Email:
smmart@ohsu.edu
Investigator:
Last name:
Lara E. Davis
Email:
Principal Investigator
Start date:
January 1, 2025
Completion date:
June 30, 2033
Lead sponsor:
Agency:
OHSU Knight Cancer Institute
Agency class:
Other
Collaborator:
Agency:
Oregon Health and Science University
Agency class:
Other
Collaborator:
Agency:
AstraZeneca
Agency class:
Industry
Collaborator:
Agency:
Eli Lilly and Company
Agency class:
Industry
Source:
OHSU Knight Cancer Institute
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06630325
