HCQ+ADC vs ADC in the Treatment of Advanced Breast Cancer

Sponsor
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Study ID
NCT06328387
Phase
PHASE1/PHASE2
Status
Unknown

Conditions

Eligibility Criteria

Sex
FEMALE
Age
18 Years - 70 Years
Healthy Volunteers
Not accepted

Interventions

  • Hydroxychloroquine — DRUG
    The dosage of hydroxychloroquine is determined based on the dose escalation study, and the appropriate administration method will be determined based on this result.
  • Sacituzumab Govitecan — DRUG
    Sacituzumab govitecan is a monoclonal antibody, called sacituzumab, linked to a chemotherapy drug, called govitecan. Sacituzumab is a form of targeted therapy because it attaches to specific molecules on the surface of cancer cells, known as Trop-2 receptors, and delivers govitecan to kill them.
  • Trastuzumab Deruxtecan — DRUG
    Trastuzumab-deruxtecan is a human HER2-directed antibody-drug conjugate (ADC) composed of humanized anti-HER2 immunoglobulin G1 (IgG1) monoclonal antibody (mAb) with the same amino acid sequence as trastuzumab, covalently linked to the membrane-permeable topoisomerase I inhibitor payload, DXd, an exatecan derivative, via a stable tetrapeptide-based linker, selectively cleaved within tumor cells.

Study Details

Advanced breast cancer is a special subtype of human breast cancer. Conventional guidelines recommend chemotherapy combined with other adjuvant therapies for this subtype of patients. However, the choice of treatment for these patients after treatment progress is a research hotspot in this field. Trastuzumab Deruxtecan (T-DXd) and Sacituzumab Govitecan (SG) are new ADC drugs targeting HER2 or TROP-2 with high efficacy and low toxicity after the progress of first-line treatment. The autophagy agents hydroxychloroquine or chloroquine has become the only FDA (Food and Drug Administration) approved autophagy inhibitor, and hydroxychloroquine and antibody-drug conjugate(ADC) may have synergistic effects based on the previous work results of our research group. Therefore,we envisage that Trastuzumab Deruxtecan(T-DXd) or Sacituzumab Govitecan (SG) combined with hydroxychloroquine(HCQ) in the treatment of advanced breast cancer in clinical practice has the advantages of improving efficacy and survival. To this end, we intend to conduct a prospective,multi-center, phase I/II clinical trial to evaluate the efficacy and safety of T-DXd or SG in combination with HCQ in patients with advacned breast cancer.

Key Dates

Start date
Jan 29, 2024
Status verified
Mar 2024
Primary completion
Feb 1, 2026
Completion
Mar 1, 2026

Study Design

Enrollment
120 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Other: Sacituzumab Govitecan
    Sacituzumab Govitecan (SG) is given by intervenous route, 10 mg/kg on day 1 and day 8 of 21-day treatment cycles. Patient will receive treatment until disease progression, unacceptable toxicity, or decision to withdraw its participation.
  • Experimental: Hydroxychloroquine Combined With Sacituzumab Govitecan
    The dosage of hydroxychloroquine is determined based on the dose escalation study, and the appropriate administration method will be determined based on this result. Sacituzumab Govitecan (SG) is given by intervenous route, 10 mg/kg on day 1 and day 8 of 21-day treatment cycles. Patient will receive treatment until disease progression, unacceptable toxicity, or decision to withdraw its participation.
  • Other: Trastuzumab Deruxtecan
    Patients will receive T-DXd at 5.4 mg/kg administered as an intravenous (IV) infusion every three-weeks (Q3W) until disease progression, unacceptable toxicity, death, or discontinuation from the study.
  • Experimental: Hydroxychloroquine Combined With Trastuzumab Deruxtecan
    The dosage of hydroxychloroquine is determined based on the dose escalation study, and the appropriate administration method will be determined based on this result. Patients will receive T-DXd at 5.4 mg/kg administered as an intravenous (IV) infusion every three-weeks (Q3W) until disease progression, unacceptable toxicity, death, or discontinuation from the study.

Primary Outcome Measure

Dose Limiting Toxicity, DLT [ Time Frame: 3 weeks ]

Central Contacts

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