A Phase Ib/III, Open-label, Randomised Study of Capivasertib Plus CDK4/6 Inhibitors and Fulvestrant Versus CDK4/6 Inhibitors and Fulvestrant in Hormone Receptor-Positive and Human Epidermal Growth Factor Receptor 2-Negative Locally Advanced, Unresectable or Metastatic Breast Cancer (CAPItello-292)
Study Identifier:
D361DC00001
CT.gov Identifier:
EudraCT Identifier:
EU Trial (CTIS) Number:
Study Contact Information:
Recruiting
Considering participating in a START clinical trial?
Study Summary
To evaluate the efficacy, safety and the degree of added benefit of capivasertib combined with palbociclib and fulvestrant in participants with endocrine-resistant locally advanced (inoperable) or metastatic HR+/HER2- breast cancer.
To examine the safety, tolerability and clinical benefit of adding AKT inhibition (with capivasertib) to combined CDK4/6 inhibition (with palbociclib) and ET (with fulvestrant) for patients with ET-resistant HR+/HER2- ABC
To demonstrate the superiority of capivasertib versus control in patients with HR+/HER2- locally advanced or metastatic breast cancer (overall population) by assessing PFS
To assess the efficacy of the addition of capivasertib to fulvestrant and the investigator’s choice of CDK4/6 inhibitors (either palbociclib or ribociclib) in patients with HR+/HER2− ABC following recurrence or progression on or within 12 months of the end of (neo)adjuvant endocrine therapy (HER2− defined as immunohistochemistry [IHC] 0, or 1-positive or IHC2-positive/in situ hybridization-negative)
Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Breast Cancers
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
Phase III
Sex
Female & Male
Age
18 - 99 Years
Study Drug
Drug: Experimental: Capivasertib Plus Palbociclib and Fulvestrant Capivasertib Plus Palbociclib and Fulvestrant (Ph 1b) Drug: Capivasertib Phase Ib: Capivasertib 320 mg/ 400 mg administered PO BD 4 days on /3 days off per week for 4 weeks (28 days cycle) Phase III:: Capivasertib, administered PO BD 4 days on / 3 days off per week for 4 weeks (28 days cycle) at the dose confirmed in the phase Ib portion Drug: Fulvestrant Phase Ib and Phase III: 500 mg (2 injections of 250 mg) on Day 1 of Weeks 1 and 3 of Cycle 1, and then on Day 1, Week 1 of each cycle thereafter Drug: Palbociclib Phase Ib: 100 mg/ 125 mg. Once daily for 21 consecutive days followed by 7 days off treatment to comprise a complete 28-day cycle Phase III: Administered once daily for 21 days of 28-day cycle, at the dose of 125 mg. Experimental: Capivasertib Plus Ribociclib and Fulvestrant Capivasertib Plus Ribociclib and Fulvestrant (Ph 1b) Drug: Ribociclib Phase Ib: 200 mg/ 400 mg/ 600 mg. Once daily for 21 consecutive days followed by 7 days off treatment to comprise a complete 28-day cycle Phase III: Administered once daily for 21 days of 28-day cycle, at the dose confirmed in the phase 1b portion. Experimental: Capivasertib Plus Abemaciclib and Fulvestrant Capivasertib Plus Abemaciclib and Fulvestrant (Ph 1b) Drug: Abemaciclib Phase Ib: 50 mg/ 100 mg/ 150 mg. Twice daily for 28 consecutive days to comprise a complete 28-day cycle Experimental: Capivasertib Plus Fulvestrant and Investigator's choice of CDK4/6i (palbociclib or ribociclib) Capivasertib Plus Fulvestrant and Investigator's choice of CDK4/6i (palbociclib or ribociclib) (Ph III) Drug: Capivasertib Phase Ib: Capivasertib 320 mg/ 400 mg administered PO BD 4 days on /3 days off per week for 4 weeks (28 days cycle) Phase III:
Study Status
Indicates the current recruitment status or the expanded access status
Recruiting
Requirements information
Inclusion criteria
- Key inclusion criteria for both phases: Adult females (pre-/peri-/ and post-menopausal), and adult males. Histologically confirmed HR+/ HER2- breast cancer determined from the most recent tumour sample (primary or metastatic) per the American Society of Clinical Oncology and College of American Pathologists guideline. To fulfil the requirement of HR+ disease, a breast cancer must express ER with or without co-expression of progesterone receptor. Eligible for fulvestrant therapy and at least one of the following: palbociclib, ribociclib, or abemaciclib, as per local investigator assessment. Previous tolerance to specific CDK4/6 inhibitors and dose levels required. Adequate organ and bone marrow functions. Consent to provide a mandatory FFPE tumour sample. Key inclusion criteria only for phase III: Previous treatment with an ET (tamoxifen, AI, or oral SERD) as a single agent or in combination, with radiological evidence of breast cancer recurrence or progression while on, or within 12 months of, completing a (neo)adjuvant ET regimen. Provision of mandatory blood samples at screening for central testing using an investigational ctDNA test to be stratified based on PIK3CA/AKT1/PTEN status. Be eligible for fulvestrant and at least one out of palbociclib or ribociclib (depending on the available CDK4/6i options at time of enrolment), as per local investigator assessment. Have measurable lesion(s) according to Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST v1.1) or, in the absence of measurable disease, lytic or mixed bone lesions that can be assessed by computed tomography (CT) or magnetic resonance imaging (MRI)..
- CFDA:
- 1Able to sign informed consent forms, including complying with the requirements and limitations listed in the ICF and this Clinical Study Protocol (CSP).2Before conducting any necessary research-specific procedures, sampling, and analysis, a written ICF must be signed and dated.3Before collecting optional samples for genetic and/or biomarker analysis, an informed consent form for optional genes and/or biomarkers should be signed and dated. This informed consent form should be signed at the time of final screening. If these samples are not collected at the time of final screening for any reason, they may be collected at any time before the follow-up visit following treatment/disease relapse. Note: There will be no penalty or loss of benefit if a subject refuses to participate in optional exploratory genetic studies and/or optional biomarker studies. Subjects may still participate in other parts of this study.4At the time of screening, the participants must be ≥18 years old and exceed the legal age of adulthood specified in their local country.5Subjects with radiographic or clinical evidence of recurrence or progression, or metastatic or locally advanced disease that is intolerant to previous/current treatment; locally advanced disease that cannot be surgically removed for curative purposes (subjects who are deemed suitable for surgery or ablation after potential tumor downstaging following treatment with investigational drugs are not eligible for inclusion).6According to the guidelines of the American Society of Clinical Oncology and the American College of Pathologists, HR+/HER2- breast cancer is defined as a histologically confirmed diagnosis using the latest (primary or metastatic) tumor sample (Hammond et al 2010; Wolff et al 2018). To meet the criteria for HR+ disease, the patient's breast cancer must express ER, with or without co-expression of the progesterone receptor. Therefore, a tumor must meet the following criteria: (a) ER+ is defined as ≥1% of tumor cells being positive for ER staining using immunohistochemistry (IHC), or if the percentage cannot be obtained, an Allred IHC score ≥3/8; (b) Progesterone receptor positive is defined as ≥1% of tumor cells being positive for progesterone receptor staining using IHC, or if the percentage cannot be obtained, an Allred IHC score ≥3/8; or progesterone receptor negative is defined as <1% of tumor cells being positive for progesterone receptor staining using IHC, or if the percentage cannot be obtained, an Allred IHC score ≤2/8; or progesterone receptor status is unknown; and (c) HER2- is defined as an IHC intensity of 0 or 1+, or an IHC intensity of 2+ with no evidence of amplification shown by in situ hybridization (ISH).7Good organ and bone marrow function is defined as follows. Criteria “a”, “b”, and “c” are not met if the patient received a blood transfusion, infusion, or growth factor support within 14 days prior to the first dose. (a) Hemoglobin ≥ 9.0 g/dL. Note: Any blood transfusion must be performed > 14 days prior to a hemoglobin measurement of ≥ 9.0 g/dL (≥ 5.59 mmol/L). (b) Absolute neutrophil count ≥ 1.5 × 10⁹/L. (c) Platelet count ≥ 100 × 10⁹/L. (d) Total bilirubin (TBL) ≤ 1.5 × Upper Limit of Normal (ULN), or < 3 × ULN if Gilbert's syndrome (hyperunionized bilirubinemia) is recorded. (e) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN; ALT and AST ≤ 5 × ULN are permissible if the subject has liver metastases. (f) Creatinine clearance (CrCL) calculated by Cockcroft-Gault (using actual body weight) >50 mL/min;8Subjects should be able to take and swallow medication orally.9The Eastern Cooperative Oncology Group (ECOG)/World Health Organization (WHO) performance status score is 0 or 1.10Life expectancy ≥ 12 weeks.11Adult women (premenopausal/perimenopausal/postmenopausal women) and adult men: (a) Premenopausal women (and perimenopausal women, i.e., those not meeting the postmenopausal criteria as defined below) who are eligible for LHRH agonist therapy are eligible for this study. Subjects should begin combination therapy with an LHRH agonist on or before day 1 of cycle 1 and must agree to continue receiving LHRH agonist therapy throughout the study. (b) Postmenopausal women are defined as those who meet at least one of the following criteria: o Age ≥ 60 years o Previous bilateral salpingectomy o Age < 60 years at screening and amenorrhea < 12 months (continuous), and follicle-stimulating hormone (FSH) and estradiol test results are within the postmenopausal range defined by the local laboratory o Age < 60 years and amenorrhea ≥ 12 months (continuous) Note: Women < 60 years at screening who have amenorrhea ≥ 12 months due to chemotherapy should undergo FSH and estradiol testing. If both FSH and estradiol test results are within the postmenopausal range defined by the local laboratory, FSH and estradiol testing should be repeated consecutively according to the National Comprehensive Cancer Network (NCCN) and/or local guidelines to ensure postmenopausal status. Because fulvestrant is structurally similar to estradiol, fulvestrant can interfere with estradiol values measured by immunoassay, leading to a false positive for elevated estradiol levels (FASLODEX SmPC); local guidelines should be followed for interpretation. Note: The menstrual status of subjects receiving ovarian function suppression (OFS) treatment cannot be determined. If a subject currently using OFS is enrolled in the study, they must maintain LHRH agonist use throughout the study treatment period. Note: If a woman is found to be premenopausal at screening or at any time during the study, LHRH agonist use and appropriate contraception must be initiated (Appendix G).12Subjects must not be breastfeeding, and women of childbearing potential (premenopausal and perimenopausal women) must have a negative pregnancy test result before starting medication. Women of childbearing potential who are not completely abstaining (i.e., avoiding heterosexual intercourse throughout the entire risk period relevant to the study intervention) and plan to have active sexual relations with an uncontraceptive male partner must use a highly effective method of contraception (Table 28) in combination with barrier methods (male condoms, female condoms, cervical caps, spermicide-containing cervical caps, or spermicide-containing contraceptive sponges). This method of contraception should be continued from the start of the study and throughout the duration of treatment until the end of systemic exposure (2 years after the last dose of fulvestrant, or 4 weeks after the last dose of capivasertib, or 3 weeks after the last dose of CDK4/6i [palbociclib, reboxil, or abeciclib], whichever occurs later). Note: The contraceptive requirement for the drug with the longest systemic exposure should always be followed, even if that drug is not the last treatment to be discontinued.13Unsterile male subjects (including those sterilized by methods other than bilateral orchiectomy [e.g., vasectomy]) who intend to have sexual intercourse with a fertile female partner must use an acceptable method of contraception, such as a male condom plus spermicide (or condoms only in countries where spermicides are not approved) from the start of the study and throughout the study duration until the end of systemic exposure (2 years after the last dose of fulvestrant, or 16 weeks after the last dose of capivasertib, or 14 weeks after the last dose of palbociclib, or 90 days after the end of systemic exposure to reboxil or abecilibil [5 half-lives], whichever occurs later). (See Appendix G). Note: The contraceptive requirement for the drug with the longest systemic exposure should always be followed, even if that drug is not the last treatment to be discontinued. If the male subject intends to have children in the future, sperm freezing is recommended before starting study treatment. Note: The (fertile) female partner of the male subject must also use a highly effective method of contraception during this period (see Appendix G 3).14According to local researchers' assessment, participants must be able to receive fulvestrant and either palbociclib or reboxiclib (at least one of these).15Subjects who have received (neo)adjuvant endocrine therapy (monotherapy or combination therapy) should have radiographic evidence of breast cancer recurrence or progression within 12 months during or after (neo)adjuvant endocrine therapy (tamoxifen, AI, or oral SERD).16In the imaging tumor assessment, subjects must: (a) have at least one lesion that has not previously received radiotherapy, whose long axis is ≥10 mm (excluding lymph nodes, whose short axis must be ≥15 mm) and which can be accurately measured by computed tomography (CT) or magnetic resonance imaging (MRI) at baseline, and which is suitable for accurate repeat measurement; or (b) in the absence of measurable lesions as specified above, have at least one osteolytic or mixed (osteolytic + sclerotic) bone lesion that can be assessed by CT or MRI; subjects who do not have measurable lesions and only have sclerotic/osteoblastic bone lesions are not eligible.17Please submit and provide the required FFPE tumor samples for central testing. FFPE tissue blocks from tumor samples (primary or recurrent cancer) collected most recently prior to randomization are preferred. If such tissue blocks are unavailable, provide 30 (at least 20) freshly cut, unstained, serial tumor sections. See the Diagnostic Examination Manual for tissue requirements for next-generation sequencing (NGS) analysis. For the Phase III portion of this study, local pathology QC must be completed prior to randomization to ensure samples are suitable for NGS analysis. Note: Tumor sample collection in China will be performed in accordance with local regulatory approvals.18As required by the laboratory manual, screening blood samples must be provided and centrally tested using an experimental ctDNA assay. Subjects will be stratified according to their PIK3CA/AKT1/PTEN status.
Exclusion criteria
- History of another primary malignancy except for malignancy treated with curative intent with no known active disease ≥ 2 years before the first dose of study intervention and of low potential risk for recurrence. Radiotherapy within 2 weeks prior to study treatment initiation. Major surgery or significant traumatic injury within 4 weeks of the first dose of study treatment. Persistent toxicities (CTCAE Grade >1) caused by previous anticancer therapy, excluding alopecia. Participants with irreversible toxicity that is not reasonably expected to be exacerbated by study intervention may be included (eg, hearing loss or peripheral sensory neuropathy) after consultation with the AstraZeneca study physician. Spinal cord compression, brain metastases or leptomeningeal metastases unless these lesions are definitively treated (eg. radiotherapy, surgery) and clinically stable off steroids for management of symptoms for at least 4 weeks prior to study treatment initiation. Any of the following cardiac criteria at screening: (a). Mean resting corrected QT interval (QTcF): (i) Participants to be treated with palbociclib:: QTcF ≥ 470 ms obtained from the average of 3 consecutive (triplicate) ECGs (ii) Participants to be treated with ribociclib: QTcF ≥ 450 ms obtained from the average of 3 consecutive (triplicate) ECGs (iii) Participants to be treated with abemaciclib (Phase Ib only): QTcF ≥ 470 ms obtained from the average of 3 consecutive (triplicate) ECGs (b). Any clinically important abnormalities in cardiac rhythm, conduction or morphology of resting ECG (eg, complete left bundle branch block, third-degree heart block) (c). Any factors that increase the risk of QTc prolongation or risk of arrhythmic events (d). Experience of any of the following procedures or conditions in the preceding 6 months: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, unstable angina pectoris, congestive heart failure New York Heart Association (NYHA) grade ≥ 2 (e). Uncontrolled hypotension (f) uncontrolled hypertension (g). Cardiac ejection fraction outside institutional range of normal or < 50% (whichever is higher) uncontrolled or high grade or symptomatic arrhythmia and atrial fibrillation Any of these clinically significant abnormalities of glucose metabolism at screening: . diabetes mellitus type I or type II requiring insulin treatment . Glycated haemoglobin (HbA1c) ≥ 8.0% (63.9 mmol/mol) Previous allogeneic bone marrow transplant or solid organ transplant. Key exclusion criteria for the phase III only: Any prior treatment with, AKT, PI3K or mTOR inhibitors. Prior treatment with CDK4/6 inhibitors in the metastatic setting (prior CDK4/6 inhibitors permitted in the adjuvant setting provided there was a CDK4/6i treatment free interval of at least 12 months). More than 1 line of chemotherapy for metastatic disease. Any line of endocrine-based therapy for inoperable locally advanced or metastatic disease.
- CFDA:
- 1Other history of primary malignancy, except for the following: radically cured malignancy, no known active disease for ≥2 years prior to the first administration of the study intervention, and low potential risk of recurrence. Exceptions include cervical carcinoma in situ, stage I endometrioid uterine cancer, or non-melanoma skin cancer (i.e., basal cell carcinoma and squamous cell carcinoma of the skin) that have received potentially radical treatment.2The patient received radiation therapy within two weeks prior to the start of the study treatment.3Those who have undergone major surgery or suffered significant trauma within 4 weeks prior to the first administration of the study intervention, or those who are expected to undergo major surgery during the study period.4Subjects with non-regressed adverse events >CTCAE grade 1 due to prior anticancer therapy, excluding alopecia, are eligible for enrollment. Subjects experiencing grade 1 anemia or neutropenia are only eligible if they have not received growth factor therapy or blood transfusions. Subjects experiencing irreversible toxicities (such as hearing loss or peripheral sensory neuropathy) that are not expected to be exacerbated by the study intervention may be enrolled after consultation with the AstraZeneca clinical team.5Spinal cord compression, brain metastases, or leptomeningeal metastases are not permitted unless these lesions have been treated radically (e.g., with radiation therapy or surgery) for at least 4 weeks prior to the start of the study, are clinically stable, and do not require steroid treatment for metastasis-related symptoms. Note: Steroid treatment/prevention of post-radiotherapy sequelae is permitted, but the lowest effective dose should be used.6Subjects meeting any of the following cardiac function criteria at screening: (a) Mean resting corrected QT interval (QTcF): (i) Subjects receiving palbociclib: Mean QTcF ≥ 470 ms from 3 consecutive (repeated) ECGs (ii) Subjects receiving reboxilib: Mean QTcF ≥ 450 ms from 3 consecutive (repeated) ECGs (iii) Subjects receiving abexicillin (Phase Ib only): Mean QTcF ≥ 470 ms from 3 consecutive (repeated) ECGs (b) Any clinically significant abnormality in cardiac rhythm, conduction, or morphology (including but not limited to: complete left bundle branch block, second- or third-degree atrioventricular block, clinically significant bradycardia (HR < 50 bpm) without a pacemaker, or sick sinus syndrome without a pacemaker). (c) Presence of any factors that increase the risk of QTc interval prolongation or arrhythmic events, such as heart failure, clinically significant left ventricular hypertrophy, electrolyte disturbances (potassium [especially hypokalemia], magnesium, calcium, and phosphorus; electrolyte disturbances may be corrected for participation in the study), potential torsades de pointes (TdP), congenital long QT syndrome, family history of unexplained sudden death in a person under 40 years of age. (d) Underwent any of the following procedures or developed any of the following conditions within the past 6 months: coronary artery bypass grafting, angioplasty, stent placement, myocardial infarction, unstable angina, or congestive heart failure ≥2 of the New York Heart Association (NYHA) classification. (e) Uncontrolled hypotension – systolic blood pressure (SBP) < 90 mmHg and/or diastolic blood pressure (DBP) < 50 mmHg. (f) Uncontrolled hypertension – SBP > 160 mmHg and/or DBP > 100 mgHg (g) Echocardiographic (or multiple-gated acquisition [MUGA] scan, if echocardiography is not possible or the results are inconclusive) shows a cardiac ejection fraction that is outside the normal range set by the research center or <50% (whichever is higher), unless the investigator considers the condition to be stable and clinically insignificant.7A history of symptomatic or treatment-required (CTCAE grade 3) arrhythmias (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia), symptomatic or uncontrolled atrial fibrillation after treatment, or asymptomatic persistent ventricular tachycardia. Subjects with atrial fibrillation controlled by medication or a pacemaker-controlled arrhythmia may be permitted to participate in the study, based on the investigator's judgment and after consultation with a cardiologist (recommended). The use of antiarrhythmic drugs (Class I or III) that can prolong the QTc interval is not permitted.8Clinically significant glucose metabolism abnormalities as defined below were present at screening: (a) Type 1 or Type 2 diabetes patients requiring insulin therapy; (a) HbA1c ≥ 8.0% (63.9 mmol/mol).9Intractable nausea and vomiting, malabsorption syndrome, previous major bowel resection, or chronic gastrointestinal diseases and other conditions that impair the absorption, distribution, metabolism or excretion of any IMP.10Subjects receiving abexicillin (Phase Ib only): Any comorbidity that the investigator considers to be a clinically significant increase in the likelihood or severity of diarrhea. Known coagulation disorders (such as bleeding disorders) or anticoagulant therapy that interferes with intramuscular fulvestrant administration.11Previously received allogeneic bone marrow transplant or solid organ transplant.12Severe, uncontrolled immunodeficiency syndrome.13"Based on the investigator's judgment, evidence of any serious or uncontrolled systemic disease, including uncontrolled hypertension, or active infection including hepatitis B, hepatitis C, and uncontrolled human immunodeficiency virus (HIV). Please refer to the WHO guidelines for the definition of active hepatitis B and C infection (https://www.who.int/publications/i/item/9789241549981). Chronic disease screening is not required. HIV-infected individuals must meet the following criteria: (a) CD4+ T cell count ≥ 350 cells/mL and HIV viral load < 400 copies/mL; both criteria must be checked within 4 weeks prior to starting study treatment and during the current antiretroviral therapy (ART) regimen. (b) History of opportunistic infection within the previous 12 months. (c) ART > 4 weeks (to ensure tolerability of ART and to ensure its toxicity is not confounded by the toxicity of the study drug). If a subject is not receiving ART and is deemed unsuitable to start ART, please consult the AstraZeneca medical team. (d)" For a list of prohibited concomitant medications (including some HIV antiretroviral drugs), please refer to Appendix I.14Active tuberculosis infection (clinical assessment may include clinical history, physical examination and imaging results, or tuberculosis testing performed in local clinical practice). Tuberculosis screening is not required.15History of hypersensitivity to any IMP or active or inactive excipients of drugs with chemical structures or classes similar to any IMP.16Evidence of dementia, altered mental state, or any mental illness may prevent the understanding or provision of informed consent.17Any disease, metabolic disorder, physical examination result, or clinical laboratory test result that may affect the interpretation of results, increase the risk of treatment complications for subjects, or affect the acquisition of informed consent, or that the investigator believes that a certain disease or condition that would preclude the use of the investigational drug can be reasonably inferred from the above diseases or results.18The study investigated the use of drugs known to significantly prolong the QT interval and drugs associated with TdP within 5 half-lives prior to the first dose of the treatment.19The precautions and limitations described in Section 6.5.2 cannot be complied with.20Patients must not have received any other chemotherapy or anticancer drug treatment (excluding current endocrine therapy) within 2 weeks prior to the first dose of study treatment, or any antibody-based anticancer drug treatment within 4 weeks prior. Chronic immunosuppressive therapies other than steroids should also be avoided.twenty oneParticipation in another clinical study, receiving study treatment or using study medical devices within 4 weeks prior to the first dose of study treatment, or being enrolled in another clinical study concurrently, unless the study is an observational (non-interventional) clinical study or is in the follow-up period of an interventional study.twenty twoUse a potent (intermediate for Phase Ib) CYP3A4 inhibitor or inducer for 2 weeks prior to the first dose of study treatment (3 weeks for St. John's wort). Weak CYP3A4 inhibitors are permitted for Phase Ib and Phase III, but the dose should not be changed within 1 week prior to the first dose of study treatment in the Phase Ib portion. Note that some CYP3A substrates may require adequate elution or dose reduction before initiating capivasertib administration. See Appendix I for guidelines.twenty threePersonnel involved in the design and/or implementation of this study (applicable to AstraZeneca staff and/or research center staff).twenty fourSubjects deemed unlikely by the researchers to comply with the research procedures, limitations, and requirements are not eligible to participate in this study.25Being pregnant (confirmed by a positive pregnancy test result) or breastfeeding.26Based on the researcher's best judgment, the subject's disease burden (e.g., symptomatic visceral disease that may be life-threatening in the short term) makes them unsuitable for endocrine therapy.27Any endocrine therapy for unresectable locally advanced or metastatic disease. Note 1: If endocrine therapy is attempted to downstage locally advanced tumors in patients without metastatic disease (neoadjuvant therapy), and the tumor is subsequently surgically treated, this treatment is not considered first-line therapy for ABC. Conversely, if the tumor remains unresectable, this treatment should be considered first-line therapy for ABC. Note 2: Endocrine maintenance therapy is permitted after chemotherapy for ABC if there is no disease progression, and it is not considered a separate line of treatment for ABC. Note 3: Adjuvant endocrine therapy is not considered first-line therapy for ABC. Furthermore, changing medications in patients without disease progression does not constitute a new line of treatment.28First-line or higher chemotherapy for unresectable locally advanced or metastatic disease. Note 1: Chemotherapy regimens discontinued due to toxicity during the first dose or within 6 weeks after administration (with a maximum of one cycle administered and no clinical or radiographic evidence of disease progression at the start of subsequent treatment) are not considered first-line treatment. Note 2: Adjuvant and neoadjuvant chemotherapy are not classified as first-line, ABC, or higher chemotherapy lines. Note 3: Antibody-drug conjugates are classified as chemotherapy lines.29Patients have previously received or concurrently received systemic AKT, PI3K, or mTOR inhibitor therapy.30Subjects with prior CDK4/6 inhibitors (e.g., palbociclib, reboxiclib, abeciclib, or an unapproved CDK4/6 inhibitor) for metastatic disease are eligible for enrollment. Note: Subjects who have received CDK4/6 inhibitors in (neo)adjuvant therapy and have a disease-free interval of at least 12 months (i.e., at least 12 months between the last day of CDK4/6 inhibitor treatment and the date of relapse) and whom the investigator deems suitable for the study treatment of RP3D are eligible for enrollment.
Clinical Study Information for Healthcare Providers
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Study Locations
Location
Investigator
Status
Condition(s) Treated at Site
Location
START San Antonio
San Antonio, TX, United States, 78229
Investigator
Muralidhar Beeram
Status
Recruiting
Condition(s) Treated at Site
Breast Cancers