NeoAdjuvant Therapy With Trastuzumab-deruxtecan Versus Chemotherapy+Trastuzumab+Pertuzumab in HER2+ Early Breast Cancer (ADAPTHER2-IV)
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ClinicalTrials.gov Identifier: NCT05704829 |
Recruitment Status :
Not yet recruiting
First Posted : January 30, 2023
Last Update Posted : September 21, 2023
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Tracking Information | ||||||||||||||||
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First Submitted Date ICMJE | December 28, 2022 | |||||||||||||||
First Posted Date ICMJE | January 30, 2023 | |||||||||||||||
Last Update Posted Date | September 21, 2023 | |||||||||||||||
Estimated Study Start Date ICMJE | December 2023 | |||||||||||||||
Estimated Primary Completion Date | June 2026 (Final data collection date for primary outcome measure) | |||||||||||||||
Current Primary Outcome Measures ICMJE |
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Original Primary Outcome Measures ICMJE | Same as current | |||||||||||||||
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Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Same as current | |||||||||||||||
Current Other Pre-specified Outcome Measures | Not Provided | |||||||||||||||
Original Other Pre-specified Outcome Measures | Not Provided | |||||||||||||||
Descriptive Information | ||||||||||||||||
Brief Title ICMJE | NeoAdjuvant Therapy With Trastuzumab-deruxtecan Versus Chemotherapy+Trastuzumab+Pertuzumab in HER2+ Early Breast Cancer | |||||||||||||||
Official Title ICMJE | NeoAdjuvant Dynamic Marker - Adjusted Personalized Therapy Comparing Trastuzumab-deruxtecan Versus Pacli-/Docetaxel+Carboplatin+Trastuzumab+Pertuzumab in HER2+ Early Breast Cancer | |||||||||||||||
Brief Summary | ADAPT-HER2-IV will address question of optimal neoadjuvant therapy in patients with less advanced -HER2+ EBC. ADAPT-HER2-IV is planned as a superiority trial to demonstrate higher pCR rates in both clinically relevant subgroups of low-intermediate risk HER2+ EBC. Moreover, it aims to demonstrate excellent survival in patients treated by T-DXd (with the use of standard chemotherapy at investigator´s decision restricted only to patients with substantial residual tumour burden after T-DXd-treatment). |
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Detailed Description | As the ADAPT-trials have clearly shown, pCR after 12 weeks of therapy, independent of the specific de-escalated neoadjuvant regimen and independent of further use of systemic chemotherapy, is an independent predictor of excellent prognosis4,19, also in patients treated by an antibody-drug conjugate alone (T-DM1), or in those receiving pertuzumab+trastuzumab+/-weekly paclitaxel. In contrast to the adjuvant setting, none of the neoadjuvant trials so far has focused on HER2+ patients with a low-intermediate risk profile (e.g., node-negative patients with cT1-2 tumours). The ADAPT-HER2-IV trial aims to close this evidence gap. Since there is some uncertainty about the optimal treatment duration in intermediate- to high-risk HER2+ EBC (e.g., tumour size >3 cm), we recommend using a longer 18-week taxane-based treatment (+/- carboplatin, at investigator´s decision) due to a large body of evidence for taxane + carboplatin combinations in patients in locally advanced stages. Antibody-drug conjugates appear to be ideal candidate drugs for a "de-escalated" treatment due to their favourable safety (reduced alopecia, polyneuropathy rates, etc.) and a high efficacy profile (e.g., comparable pCR rates after 18 weeks of T-DM1 and taxane+pertuzumab+trastuzumab in the PREDIX HER2 trial20). Similarly to the classical chemotherapy landscape, optimal duration of antibody-drug conjugate-based neoadjuvant therapy remains unclear. pCR rates of around 40% to 60% were observed after 12 and 18 weeks of T-DM1 treatment (+/-pertuzumab) in the ADAPT TP, KRISTINE and PREDIX HER2 trials in HR+/HER2+ disease21,22. Moreover, long-term survival seem to be comparable between T-DM1+pertuzumab and older chemotherapy-containing regimens (docetaxel+carboplatin+trastuzumab+pertuzumab) despite of higher local progression rates and lower pCR in one study22. Trastuzumab-deruxtecan (T-DXd) has shown promising activity in a small cohort of metastatic patients, including both HER2+ and HER2-low BC, pre-treated with several lines of therapy. Doi et al. reported overall response rates (ORR) of 58% and a disease control rate of 100% with overall survival at 12 months at in HER2+ disease pre-treated by T-DM1+/-pertuzumab in a late line setting23. T-DXd-therapy was associated with a manageable safety profile. Recently, clearly higher efficacy of T-DXd vs. T-DM1 was shown in second line metastatic breast cancer (MBC) in the DESTINY-03 trial24. Median progression free survival was not reached in T-DM1-arm vs. 6.8 months in the T-DXd-arm. This effect was independent of hormone receptor status, prior pertuzumab treatment, visceral metastases, number of prior therapy lines and presence of brain metastases. ORR was doubled (34.2 vs. 79.7%), favouring the T-DXd arm. |
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Study Type ICMJE | Interventional | |||||||||||||||
Study Phase ICMJE | Phase 2 | |||||||||||||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Crossover Assignment Intervention Model Description: This is a multicentre, interventional, prospective, two-arm, randomised, open-label, controlled (neo-)adjuvant, phase-II trial evaluating the efficacy and safety of trastuzumab-deruxtecan (T-DXd) vs. standard-of-care paclitaxel + trastuzumab + pertuzumab (PAC+T+P) in low- to intermediate-risk or docetaxel/paclitaxel + carboplatin + trastuzumab + pertuzumab in intermediate- to high-risk HER2+ early breast cancer in pre- and postmenopausal women. Masking: None (Open Label)Primary Purpose: Treatment |
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Condition ICMJE | HER2-positive Early Breast Cancer | |||||||||||||||
Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | Not Provided | |||||||||||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | ||||||||||||||||
Recruitment Status ICMJE | Not yet recruiting | |||||||||||||||
Estimated Enrollment ICMJE |
402 | |||||||||||||||
Original Estimated Enrollment ICMJE | Same as current | |||||||||||||||
Estimated Study Completion Date ICMJE | June 2028 | |||||||||||||||
Estimated Primary Completion Date | June 2026 (Final data collection date for primary outcome measure) | |||||||||||||||
Eligibility Criteria ICMJE | Inclusion Criteria: Patients eligible for inclusion in this study must meet all the following criteria:
4. Written informed consent 5. LVEF ≥ 50% within 28 days before randomisation 6. Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1 7. Adequate organ and bone marrow function within 14 days before randomisation 8. Adequate treatment washout period before randomisation (refer to protocol for detailed information) 9. Evidence of post-menopausal status or negative serum pregnancy test for females of childbearing potential (refer to protocol for detailed information) 10. Female subjects must not donate, or retrieve for their own use, ova from the time of randomisation and throughout the study treatment period, and for at least 7 months after the final study drug administration. (refer to protocol for detailed information) Exclusion Criteria: Patients eligible for inclusion in this study must not meet any of the following criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | |||||||||||||||
Accepts Healthy Volunteers ICMJE | No | |||||||||||||||
Contacts ICMJE |
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Listed Location Countries ICMJE | Germany | |||||||||||||||
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Administrative Information | ||||||||||||||||
NCT Number ICMJE | NCT05704829 | |||||||||||||||
Other Study ID Numbers ICMJE | WSG-AM12 | |||||||||||||||
Has Data Monitoring Committee | Yes | |||||||||||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Current Responsible Party | West German Study Group | |||||||||||||||
Original Responsible Party | Same as current | |||||||||||||||
Current Study Sponsor ICMJE | West German Study Group | |||||||||||||||
Original Study Sponsor ICMJE | Same as current | |||||||||||||||
Collaborators ICMJE | AstraZeneca | |||||||||||||||
Investigators ICMJE |
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PRS Account | West German Study Group | |||||||||||||||
Verification Date | September 2023 | |||||||||||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |