Trastuzumab Deruxtecan (T-DXd): Tailoring Treatment and Companion Diagnostics (CDx) by Liquid Biopsy

NCT05919212 | Unknown DMC

• 1 other identifier: 5382
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective single-center pilot study phase II non randomized designed to explore the role of liquid biopsy in metastatic HER2-positive breast cancer patients treated with Trastuzumab deruxtecan (T-Dxd) as second line treatment according to international guidelines. All eligible patients to T-Dxd as second line treatment will receive T-Dxd intravenous at dose of 5,4 mg/kg every three weeks until progression disease or unacceptable toxicities. Subjects eligible to T-Dxd, who agree to participate in the study, will undergo serial blood samples for liquid biopsy (LB) until progression disease. The timing of blood drawing will be scheduled as follows: At each T-DXd administration for the first four cycles of T-Dxd (every three weeks). The next blood drawings will be done every three cycles of T-Dxd (every 9 weeks) until the thirteenth cycle. The next blood drawings will be done every six cycles of T-Dxd (every 18 weeks) until progression disease (documented by medical imaging) For all enrolled patients with available tumour tissue from primary diagnosis or last biopsy from recurrence, tissue samples will be requested for exploratory analysis.

Conditions

Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Alterations associated with resistent to Trastuzumab Deruxtecan

  To dynamically assess circulating alterations associated with resistance to Trastuzumab Deruxtecan (T-DXd) including changes of the HER2 status by a novel approach named HER2-2D that simultaneously assesses HER2 amplification and (over)expression in blood.

  4 years

Secondary Outcomes (3)

• Molecular stratification of patients (dynamic approach by Liquid Biopsy, LB);

  4 years

• Lead Time assessment by Liquid Biopsy.

  4 years

• Association between HER2-2D and outcome in terms of progression.

  4 years

Other Outcomes (2)

• To evaluate the safety and tolerability of T-Dxd

  4 years

• To evaluate the concordance or not between mutations discovered at baseline liquid biopsy and tissue extraction mutations from primary or last available tumor tissue

  4 years

Study Arms (1)

Patients with HER2 positive Breast cancer Stage IV

EXPERIMENTAL

All eligible patients to T-Dxd as second line treatment will receive T-Dxd intravenous at dose of 5,4 mg/kg every three weeks until progression disease or unacceptable toxicities. Subjects eligible to T-Dxd and who agree to participate in the study will undergo serial blood samples for liquid biopsy (LB) until progression disease.

Diagnostic Test: HER2-D is the use of a non-invasive liquid biopsy method to non-invasively and objectively assess HER2 status at recruitment

Interventions

HER2-D is the use of a non-invasive liquid biopsy method to non-invasively and objectively assess HER2 status at recruitment DIAGNOSTIC_TEST

We study the circulating changes associated with resistance to T-DXd, including changes in HER2 status,studied through a new approach called HER2-2D that simultaneously assesses HER2 amplification and overexpression in blood

Patients with HER2 positive Breast cancer Stage IV

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must be competent and able to comprehend, sign, and date informed consent prior to any study specific procedures;
• Male or female subjects age ≥ 18 years;
• Subjects with histologically or cytologically proven diagnosis of adenocarcinoma of the breast with evidence of either locally advanced disease not amenable to resection or radiation therapy with curative intent or metastatic disease not amenable to curative therapy;
• Subjects must have confirmed, per local testing on most recent tumor tissue sample available, an HER2-positive expression, as determined according to American Society of Clinical Oncology - College of American Pathologists guidelines (as defined in the 2013 American Society of Clinical Oncology (ASCO) recommendations for HER2 testing \[7\]) with any ER and/or PgR tumor status;
• Subjects must have received no more than one line of treatment including trastuzumab plus or not pertuzumab associated to taxane in the advanced/metastatic setting or progressed within 6 months after neoadjuvant or adjuvant treatment involving a regimen including trastuzumab and taxane;
• Documented radiologic progression (during or after most recent treatment or within 6 months after completing adjuvant therapy);
• Presence of at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (see Appendix A)
• Non measurable (evaluable) bone-only disease are eligible. Evaluable bone-only disease must include at least one lytic bone lesion or a mixed lytic-blastic bone lesion; blastic only metastases are not allowed. Subjects who have had prior radiation to bone must have at least one evaluable lesion in a non-irradiated area. Patients with lesions identified only on radionucleotide bone scan are not eligible;
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1;
• Life expectancy \> 12 weeks;
• Subjects with clinically inactive brain metastases may be included in the study.
• Subjects with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of brain radiotherapy and study enrolment.
• LVEF ≥ 50% within 28 days before enrolment.
• Adequate organ and bone marrow function within 14 days before enrollment
• Adequate treatment washout period before enrolment

You may not qualify if:

• Prior treatment with an anti-HER2 Antibody Drug Conjugated (ADC)
• Uncontrolled or significant cardiovascular disease, including any of the following:
• a. History of myocardial infarction (MI) within 6 months before enrolment; b. History of symptomatic congestive heart failure (New York Heart Association Class II to IV); c. Corrected QT interval (QTc) prolongation to \> 470 ms (females) or \>450 ms (male) based on average of Screening triplicate 12-lead ECG; d. Left ventricular ejection fraction (LVEF) \< 50% within 28 d prior to enrollment
• History of non-infectious ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening.
• Lung criteria: a. Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (e.g. pulmonary emboli within three months of the study enrolment, severe asthma, severe COPD, restrictive lung disease, pleural effusion etc.); b. Any autoimmune, connective tissue or inflammatory disorders (e.g. Rheumatoid arthritis, Sjogren's, sarcoidosis etc.) where there is documented, or a suspicion of pulmonary involvement at the time of screening. Full details of the disorder should be recorded in the eCRF for patients who are included in the study; c. Prior pneumonectomy (complete)
• Spinal cord compression or clinically active central nervous system (CNS) metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms.
• Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals.
• Active primary immunodeficiency, known human immunodeficiency virus (HIV) infection, or active hepatitis B or C infection. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. Subjects should be tested for HIV prior to enrolment if required by local regulations or institutional review board (IRB)/ethics committee (EC).
• Receipt of live, attenuated vaccine (mRNA and replication deficient adenoviral vaccines are not considered attenuated live vaccines) within 30 days prior to the first dose of T-Dxd. Note: Patients, if enrolled, should not receive live vaccine during the study and up to 30 days after the last dose of study treatment.
• Multiple primary malignancies within 3 years, except adequately resected non melanoma skin cancer, curatively treated in situ disease, other solid tumors curatively treated, or contralateral breast cancer.

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead

Study Sites (1)

Fondazione Policlinico A. Gemelli - IRCCS

Rome, 00168, Italy

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Alessandra Fabi

  Fondazione Policlinico A. Gemelli - IRCCS

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alessandra Fabi

CONTACT

+390630157337; alessandra.fabi@policlinicogemelli.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 18, 2023
• First Posted: June 26, 2023
• Study Start: February 1, 2023
• Primary Completion: June 1, 2024
• Study Completion: February 1, 2026
• Last Updated: April 15, 2024

Record last verified: 2023-12

Locations

IT (1)