Breast Cancer Clinical Trial
Official title:
TACTIVE-U: An Interventional Safety and Efficacy Phase 1b/2, Open-label Umbrella Study to Investigate Tolerability, pk, and Antitumor Activity of Vepdegestrant (ARV-471/PF-07850327), an Oral Proteolysis Targeting Chimera, in Combination With Other Anticancer Treatments in Participants Aged 18 Years and Over With ER+ Advanced or Metastatic Breast Cancer, Sub-study A (ARV-471 in Combination With Abemaciclib)
The purpose of this clinical trial is to learn about the safety and effects of the study medicine (called ARV-471) when given together with other medicines for the potential treatment of advanced or metastatic breast cancer. This study is seeking participants who have breast cancer that: - is advanced, may have spread to other organs (metastatic) and cannot be fully treated by surgery or radiation therapy - is sensitive to hormonal therapy (it is called estrogen receptor positive); and - is no longer responding to previous treatments This study is divided into separate sub-studies. For Sub-Study A: All participants will receive ARV-471 and a medicine called abemaciclib. ARV-471 will be given by mouth, at home, 1 time a day. Abemaciclib will be given by mouth, at home, 2 times a day. We will examine the experiences of people receiving the study medicines. This will help us determine if the study medicines are safe and effective. Participants will continue to take ARV-471 and abemaciclib until their cancer is no longer responding, or side effects become too severe. They will have visits at the study clinic about every 4 weeks.
Status | Recruiting |
Enrollment | 40 |
Est. completion date | December 31, 2025 |
Est. primary completion date | December 31, 2025 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: - histological or cytological diagnosis of ER+ and HER2- advanced/metastatic breast cancer that is not amendable to surgical resection with curative intent (=1% ER+ stained cells on the most recent tumor biopsy). - prior anticancer therapies: at least 1 and no more than 2 lines of prior therapies for advanced/metastatic disease; 1 line of any CDK4/6 inhibitor-based regimen is required (independent of the setting eg, adjuvant or advanced/metastatic) - at least 1 measurable lesion as defined by RECIST v1.1. - ECOG PS =1. Exclusion Criteria: - visceral crisis at risk of life-threatening complications in the short term - known history of drug-induced pneumonitis or other significant symptomatic deterioration of lung functions. - newly diagnosed brain metastases, or symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease. Participants with a history of CNS metastases or cord compression are eligible if they have been definitively treated, clinically stable and discontinued anti-seizure medications and corticosteroids for at least 14 days prior to enrollment in the study. - history of any other tumor malignancies within the past 3 years, except for the following: (1) adequately treated basal or squamous cell carcinoma of the skin; (2) curatively treated in situ carcinoma of the cervix. - inflammatory breast cancer - impaired cardiovascular function or clinically significant cardiovascular diseases - concurrent administration of medications, food, or herb supplements that are strong inhibitors and strong/moderate inducers of CYP3A and drugs known to predispose to Torsade de Pointes or QT interval prolongation. - renal impairment, not adequate liver function and/or bone marrow function - known active infection |
Country | Name | City | State |
---|---|---|---|
Canada | CIUSSS- saguenay-Lac-Saint-Jean | Chicoutimi | Quebec |
Canada | Jewish General Hospital | Montreal | Quebec |
Canada | The Ottawa Hospital - General Campus | Ottawa | Ontario |
Canada | Sunnybrook Research Institute | Toronto | Ontario |
Canada | BC Cancer Vancouver | Vancouver | British Columbia |
Canada | BC Cancer Vancouver | Vancouver | British Columbia |
Italy | Azienda Ospedaliero Universitaria delle Marche | Ancona | |
Italy | Istituto di Candiolo IRCCS - Fondazione del Piemonte per l'Oncologia | Candiolo | Torino |
Italy | Humanitas Istituto Clinico Catanese | Misterbianco | Catania |
Italy | Fondazione IRCCS San Gerardo dei Tintori | Monza | Lombardia |
Italy | Istituto Nazionale Tumori IRCCS Fondazione Pascale | Napoli | Campania |
Italy | Istituto Oncologico Veneto IRCCS | Padova | |
Italy | Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sacro Cuore | Roma | Lazio |
Spain | Hospital Universitari Dexeus | Barcelona | Catalunya [cataluña] |
Spain | Hospital Universitari Vall d'Hebron | Barcelona | Barcelona [barcelona] |
Spain | Clinica Universidad de Navarra | Madrid | Madrid, Comunidad DE |
Spain | Clínica Universidad de Navarra | Madrid | Madrid, Comunidad DE |
Spain | Hospital General Universitario Gregorio Marañon | Madrid | |
Spain | Hospital Universitario 12 de Octubre | Madrid | Madrid, Comunidad DE |
Spain | Clinica Universidad de Navarra | Pamplona | Navarra |
Spain | Hospital Universitario Virgen Del Rocio | Sevilla | |
United States | Brigham and Women's Hospital | Boston | Massachusetts |
United States | Dana-Farber Cancer Institute | Boston | Massachusetts |
United States | Massachusetts General Hospital | Boston | Massachusetts |
United States | Siteman Cancer Center - West County | Creve Coeur | Missouri |
United States | Siteman Cancer Center - North County | Florissant | Missouri |
United States | U.T. MD Anderson Cancer Center | Houston | Texas |
United States | U.T. MD Anderson Cancer Center, Investigational Pharmacy Services - Unit 376 | Houston | Texas |
United States | University of Texas MD Anderson Cancer Center | Houston | Texas |
United States | Dana-Farber Cancer Institute - Chestnut Hill | Newton | Massachusetts |
United States | Stanford Women's Cancer Center | Palo Alto | California |
United States | Stanford Women's Cancer Center | Palo Alto | California |
United States | Barnes-Jewish Hospital | Saint Louis | Missouri |
United States | Siteman Cancer Center - South County | Saint Louis | Missouri |
United States | Washington University | Saint Louis | Missouri |
United States | Washington University School of Medicine | Saint Louis | Missouri |
United States | Washington University School of Medicine - Siteman Cancer Center | Saint Louis | Missouri |
United States | Siteman Cancer Center - St Peters | Saint Peters | Missouri |
United States | UCSF Medical Center at Mission Bay | San Francisco | California |
United States | Siteman Cancer Center - WUPI | Shiloh | Illinois |
United States | Moffitt Cancer Center | Tampa | Florida |
United States | Moffitt Cancer Center - International Plaza | Tampa | Florida |
United States | Moffitt Cancer Center, Richard M. Shulze Family Foundation Outpatient Center | Tampa | Florida |
Lead Sponsor | Collaborator |
---|---|
Pfizer | Arvinas Estrogen Receptor, Inc. |
United States, Canada, Italy, Spain,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Phase 1b: number of participants with dose limiting toxicities | Dose Limiting Toxicities rate for ARV-471 in combination with abemaciclib, estimated based on data from DLT-evaluable participants during the DLT observation period (Cycle 1 [28 days]). | 28 days | |
Primary | Phase 2: percentage of participants with objective response by investigator assessment | Objective response (OR) refers to confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1. as determined by investigator assessment. | Up to approximately 1 year | |
Secondary | Phase 1b and Phase 2: number of participants experiencing any AE, SAE, Treatment Related SAE | An adverse event (AE) were any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An SAE is any untoward medical occurrence that, at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitalization; was life-threatening; resulted in persistent or significant disability/ incapacity; congenital anomaly/birth defect and other important medical events. Treatment-related AE is any untoward medical occurrence attributed to study drug in a participant who received study drug. AEs were graded by the investigator according to the Common Terminology Criteria for Adverse Events (CTCAE version 5.0) and coded using MedDRA were reported. Grade 1=mild; Grade 2=moderate; Grade 3=severe and Grade 4=life-threatening or disabling and grade 5=death. |
Up to 28 days after last dose of study treatment | |
Secondary | Phase 1b and Phase 2: number of participants with lab abnormalities - Hematology and coagulation parameters | Blood samples were collected for the analysis of following hematology and coagulation parameters: hemoglobin [g/L], platelets, leukocytes, neutrophils, lymphocytes, monocytes, eosinophils and basophils [10^9/L]; partial thromboplastin time prolonged, international normalized ratio increased, prothrombin time. Number of participants with hematological and coagulation abnormalities by grade as per CTCAE version 5.0 were reported. Grade 1=mild; Grade 2=moderate; Grade 3=severe and Grade 4=life-threatening or disabling and grade 5=death. For laboratory tests without CTCAE grade definitions, results will be categorized as normal, abnormal, or not done. |
Up to 28 days after last dose of study treatment | |
Secondary | Phase 1b and Phase 2: number of participants with lab abnormalities - chemistry parameters | Blood samples were collected for analysis of clinical chemistry parameters. These included: alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, [international unit per liter (IU/L)] ; Lipase and amilase [IU/L] (limited to cycle1 only); Albumin, bilirubin, urea ,calcium, creatinine, glucose, magnesium, phosphate, uric acid, chloride, potassium and sodium [millimol per liter (mmol/L)]; eGFR [milliliter per minute (ml/min)]. Number of participants with blood chemistry abnormalities by grade as per CTCAE version 5.0 were reported. Grade 1=mild; Grade 2=moderate; Grade 3=severe and Grade 4=life-threatening or disabling and grade 5=death. For laboratory tests without CTCAE grade definitions, results will be categorized as normal, abnormal, or not done. |
Up to 28 days after last dose of study treatment | |
Secondary | Phase 1b: percentage of participants with objective response by investigator assessment | Objective response (OR) refers to confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1. as determined by investigator assessment. | Up to approximately 1 year | |
Secondary | Phase 1b and Phase 2: duration of response by investigator assessment. | Duration of Response (DoR) is defined for participants with confirmed OR (CR or PR) as the time from the first documentation of OR to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first. | Up to approximately 1 year | |
Secondary | Phase 1b and Phase2: Percentage of participants with Clinical Benefit Response by investigator assessment. | Clinical Benefit Response (CBR) is defined as the proportion of participants with Best Overall Response of confirmed CR or PR at any time, or Stable Disease (SD) =24 weeks | Up to approximately 1 year | |
Secondary | Phase 1b and Phase 2: Progression Free Survival by investigator assessment. | Progression Free Survival (PFS) is defined as the time from the date of first dose of study interventions to the date of first documentation of PD or death due to any cause, whichever occurs first. | Up to approximately 1 year | |
Secondary | Phase 2: Overall Survival | Overall Survival (OS) is defined as the time from the date of first dose of study interventions to the date of death due to any cause | Through study completion, up to approximately 3 year | |
Secondary | Phase 2:ctDNA plasma quantitative changes from pre-treatment | To assess changes from baseline levels in plasma circulating DNA (ctDNA) with treatment and to evaluate potential predictability of their associations with clinical outcome | Day 1, 29 and 57 and End of Treatment (an average of 1 year) | |
Secondary | Phase 1b: Area Under the Curve from Time Zero to end of dosing interval Evaluation of abemaciclib with or without ARV-471 | Exposure (AUCtau) of abemaciclib with and without co-administration of ARV-471 | Phase 1b: pre-dose Day -1, 1, 15, 29, 43, 57, 113, 169; 1, 2, 4, 6, 8 hours post dose on Day -1 and 15; post dose Day 29 and 43 | |
Secondary | Phase 1b: Maximum Observed Plasma Concentration (Cmax) of abemaciclib with or without ARV-471 | Concentration (Cmax) of abemaciclib with and without co-administration of ARV-471 | Phase 1b: pre-dose Day -1, 1, 15, 29, 43, 57, 113, 169; 1, 2, 4, 6, 8 hours post dose on Day -1 and 15; post dose Day 29 and 43 | |
Secondary | Phase 1b and Phase 2: Maximum Observed Plasma Concentration (Cmax) of ARV-471 | Plasma concentration of ARV-471 | Phase 1b: pre-dose Day 1, 15, 29, 43, 57, 113, 169; 1, 2, 4, 6, 8 hours post dose on Day 15; post dose Day 29 and 43. Phase 2: pre and post dose Day 15, 29 and 43; pre - dose Day 57, 113 and 169 | |
Secondary | Phase 1b and Phase 2: Maximum Observed Plasma Concentration (Cmax) of abemaciclib | Plasma concentration of abemaciclib | Phase 1b: pre-dose Day -1, 1, 15, 29, 43, 57, 113, 169; 1, 2, 4, 6, 8 hours post dose on Day -1 and 15; post dose Day 29, 43 and 57 Phase 2: pre and post dose Day 15, 29 and 43; pre - dose Day 57, 113 and 169 |
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