Testing the Combination of Two Anti-cancer Drugs, DS-8201a and AZD6738, for The Treatment of Patients With Advanced Solid Tumors Expressing the HER2 Protein or Gene, The DASH Trial : Phase 1/1B Study of DS-8201a in Combination With ATR Inhibition (AZD6738) in Advanced Solid Tumors With HER2 Expression (DASH Trial)
PRIMARY OBJECTIVES:I. Evaluate safety, tolerability, and recommended phase 2 dose (RP2D) of trastuzumab deruxtecan (DS-8201a) in combination with ceralasertib (AZD6738) in advanced solid tumors with HER2 expression. (Escalation Phase) II. Assess differential pharmacodynamic (PD) profile of tumor tissue (deoxyribonucleic acid [DNA] damage & repair) between Top1 inhibition and dual inhibition of Top1 and ATR in patients with colorectal cancer and gastroesophageal cancer with HER2 expression. (Expansion Phase)SECONDARY OBJECTIVES:I. To observe and record anti-tumor activity. II. To evaluate pharmacokinetics (PK) of DS-8201a and AZD6738 and immunogenicity of DS8201a.EXPLORATORY OBJECTIVES:I. Evaluate association between HER2 heterogeneity and response to DS-8201a plus (+) AZD6738 therapy using central protein expression assessment.II. Determine predictive biomarkers (including but not restricted to: HER2 protein levels, HER2 gene copy number, alterations of TP53, ATM and RAS) of DS-8201a + AZD6738 efficacy in advanced solid tumors (specifically colorectal cancer and gastroesophageal cancer) with HER2 expression.III. To characterize PD biomarkers for efficacy of DS-8201a + AZD6738 efficacy in advanced solid tumors (specifically colorectal cancer and gastroesophageal cancer) with HER2 expression (such as phosphorylated [p]RAD50 and SLFN11).IV. To establish a biorepository of tissue, blood and pre-clinical models (PDXs) for HER2 expressing advanced solid tumors (specifically colorectal cancer and gastroesophageal cancer).OUTLINE: This is a dose-escalation study of ceralasertib with fixed dose trastuzumab deruxtecan followed by a dose-expansion study.Patients receive trastuzumab deruxtecan intravenously (IV) over 30-90 minutes on day 1 and ceralasertib orally (PO) twice daily (BID) on days 1-7. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. NOTE: During the dose-expansion phase, the first 6 patients in each disease cohort (gastroesophageal cancer [cohort A] and colorectal cancer [cohort B]) receive only trastuzumab deruxtecan for the first cycle, followed by trastuzumab deruxtecan and ceralasertib together in subsequent cycles.After completion of study treatment, patients are followed up every 3 months for 2 years, then every 6 months for 3 years..
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Klinische Studie| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
ClinicalTrials.gov - (2024) vom: 28. März Zur Gesamtaufnahme - year:2024 |
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| Sprache: |
Englisch |
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| Links: |
Volltext [kostenfrei] |
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| Anmerkungen: |
Source: Link to the current ClinicalTrials.gov record., First posted: January 12, 2021, Last downloaded: ClinicalTrials.gov processed this data on April 03, 2024, Last updated: April 03, 2024 |
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| Study ID: |
NCT04704661 |
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| Veröffentlichungen zur Studie: |
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| PPN (Katalog-ID): |
CTG000010057 |
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| 245 | 1 | 0 | |a Testing the Combination of Two Anti-cancer Drugs, DS-8201a and AZD6738, for The Treatment of Patients With Advanced Solid Tumors Expressing the HER2 Protein or Gene, The DASH Trial |b Phase 1/1B Study of DS-8201a in Combination With ATR Inhibition (AZD6738) in Advanced Solid Tumors With HER2 Expression (DASH Trial) |
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| 500 | |a Source: Link to the current ClinicalTrials.gov record., First posted: January 12, 2021, Last downloaded: ClinicalTrials.gov processed this data on April 03, 2024, Last updated: April 03, 2024 | ||
| 520 | |a PRIMARY OBJECTIVES:I. Evaluate safety, tolerability, and recommended phase 2 dose (RP2D) of trastuzumab deruxtecan (DS-8201a) in combination with ceralasertib (AZD6738) in advanced solid tumors with HER2 expression. (Escalation Phase) II. Assess differential pharmacodynamic (PD) profile of tumor tissue (deoxyribonucleic acid [DNA] damage & repair) between Top1 inhibition and dual inhibition of Top1 and ATR in patients with colorectal cancer and gastroesophageal cancer with HER2 expression. (Expansion Phase)SECONDARY OBJECTIVES:I. To observe and record anti-tumor activity. II. To evaluate pharmacokinetics (PK) of DS-8201a and AZD6738 and immunogenicity of DS8201a.EXPLORATORY OBJECTIVES:I. Evaluate association between HER2 heterogeneity and response to DS-8201a plus (+) AZD6738 therapy using central protein expression assessment.II. Determine predictive biomarkers (including but not restricted to: HER2 protein levels, HER2 gene copy number, alterations of TP53, ATM and RAS) of DS-8201a + AZD6738 efficacy in advanced solid tumors (specifically colorectal cancer and gastroesophageal cancer) with HER2 expression.III. To characterize PD biomarkers for efficacy of DS-8201a + AZD6738 efficacy in advanced solid tumors (specifically colorectal cancer and gastroesophageal cancer) with HER2 expression (such as phosphorylated [p]RAD50 and SLFN11).IV. To establish a biorepository of tissue, blood and pre-clinical models (PDXs) for HER2 expressing advanced solid tumors (specifically colorectal cancer and gastroesophageal cancer).OUTLINE: This is a dose-escalation study of ceralasertib with fixed dose trastuzumab deruxtecan followed by a dose-expansion study.Patients receive trastuzumab deruxtecan intravenously (IV) over 30-90 minutes on day 1 and ceralasertib orally (PO) twice daily (BID) on days 1-7. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. NOTE: During the dose-expansion phase, the first 6 patients in each disease cohort (gastroesophageal cancer [cohort A] and colorectal cancer [cohort B]) receive only trastuzumab deruxtecan for the first cycle, followed by trastuzumab deruxtecan and ceralasertib together in subsequent cycles.After completion of study treatment, patients are followed up every 3 months for 2 years, then every 6 months for 3 years. | ||
| 650 | 2 | |a Carcinoma | |
| 650 | 2 | |a Breast Neoplasms | |
| 650 | 2 | |a Neoplasms | |
| 650 | 2 | |a Colorectal Neoplasms | |
| 650 | 2 | |a Adenocarcinoma | |
| 650 | 2 | |a Stomach Neoplasms | |
| 650 | 2 | |a Colonic Neoplasms | |
| 650 | 2 | |a Esophageal Neoplasms | |
| 650 | 2 | |a Endometrial Neoplasms | |
| 650 | 2 | |a Salivary Gland Neoplasms | |
| 650 | 4 | |a Study Type: Interventional | |
| 650 | 4 | |a Recruitment Status: Recruiting | |
| 650 | 4 | |a Phase: Phase 1 | |
| 650 | 4 | |a 610 | |
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