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AzTrials

Advanced Breast CancerPhase 1/2NCT06328387

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

A Phase 1/2 study testing Hydroxychloroquine, Sacituzumab Govitecan and Trastuzumab Deruxtecan in people with Advanced Breast Cancer and Metastatic Breast Cancer, run by Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University at 1 site in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 70 years, women only
What is being tested?
Hydroxychloroquine, Sacituzumab Govitecan and Trastuzumab Deruxtecan
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
120 participants
Where
1 siteChina
Study dates
29 Jan 2024to 1 Mar 2026
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Diagnosis of advanced breast cancer (female, 18 to 70 years old).
  • Pathological confirmed advanced breast cancer.
  • The patient is willing to receive SG or T-DXd treatment.
  • Failure of first-line treatment.
  • Have received no more than 3 chemotherapy schemes for metastatic breast cancer in the past.
  • ECOG physical condition score ≤ 2 points, estimated survival time of no less than 3 months.
Show all 10Show fewer
  • At least one measurable lesion should be present in the imaging examination within 2 weeks prior to enrollment; Or simple bone metastasis lesions.
  • LVEF≥50%.
  • Previous treatment related toxicity must be relieved to NCI CTCAE (version 5.0) ≤ 1 degree, AST and ALT ≤ 2.5 times the upper limit of normal value, and total bilirubin ≤ 1.5 times the upper limit of normal value.
  • Adequate reserve of bone marrow function: white blood cell count ≥ 3.0 × 10^9/L, neutrophil count ≥ 1.5 × 10^9/L; Platelet count ≥ 100 × 10^9/L; Hemoglobin ≥ 90g/L; Serum creatinine ≤ 1.5 times the upper limit of normal value.

Who cannot join

  • Patients suffer from various factors such as difficulty swallowing and chronic diarrhea, which affect medication intake and absorption.
  • Individuals with severe heart disease or discomfort, expected inability to tolerate chemotherapy, including but not limited to: fatal arrhythmias or higher-level atrioventricular block, unstable angina, clinically significant valvular heart disease, electrocardiogram showing transmural myocardial infarction, and uncontrolled hypertension.
  • Patients who are known to be allergic to the active ingredients or other components of the investigational drug.
  • Received radiotherapy, chemotherapy, endocrine therapy within 4 weeks prior to enrollment, or is currently participating in any intervention drug clinical trials.
  • Pregnant or lactating women, women of childbearing age who refuse to take effective contraceptive measures during the study period.
  • The researchers believe that patients are not suitable to participate in any other circumstances of this study, which may interfere with the accompanying diseases or conditions of the study, or have any serious medical obstacles that may affect the safety of the subjects.

Trial locations and contacts

1 site in 1 country.

Jianli J Zhao, doctorate contact

15920589334

zhaojli5@mail.sysu.edu.cn

Erwei E Song, doctorate contact

13926477694

songew@mail.sysu.edu.cn

China1 site, 1 recruiting

  • Sun Yat-sen Memorial Hospital, Sun Yat-sen University

    Guangzhou, Guangdong, 510120

    Jianli J Zhao, doctorate, 15920589334, zhaojli5@mail.sysu.edu.cn

    Recruiting

Other trials in China

About this study

Official title: Open, Controlled, Multicenter Phase I/II Clinical Study of Hydroxychloroquine in Combination With Antibody-drug Conjugate Versus Antibody-drug Conjugate for Advanced Breast Cancer.

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.

Read the detailed description

Breast cancer is the most prevalent malignant tumor in the world, and 30% of breast cancer patients will enter the advanced stage due to treatment failure. Most patients with advanced breast cancer have had distant organ metastasis, and the median progression free survival period is only 1-2 years.

In the past, advanced breast cancer patients faced the dilemma of poor survival due to the lack of precise targeted therapy. However, through a series of clinical studies, experts in the field of advanced breast cancer have successfully expanded the indications of ADC-based combination targeted therapy from the emergence of first generation ADC to the third generation ADC with "bystander effect", which has significantly prolonged the survival time of patients. 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.

Because both ADC and autophagy involve lysosomes, and the relationship between ADC and autophagy microenvironment has not been elucidated, the combination of autophagy regulators and ADC may be a treatment option that can benefit some patients more.The autophagy agents hydroxychloroquine or chloroquine has become the only FDA (Food and Drug Administration) approved autophagy inhibitor. And the synergistic effect of hydroxychloroquine and antibody-drug conjugate (ADC) has already been confirmed based on preliminary experiments of our research group. 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.

Therefore, we intend to further validate the efficacy and safety of the Autophagy inhibitor hydroxychloroquine(HCQ) in combination with the latest ADC drugs (T-DXd or SG) in a Phase I/II, randomized, controlled clinical study, in order to provide advanced breast cancer patients with a better choice of precision targeted therapy.

Being tested
Hydroxychloroquine, Sacituzumab Govitecan, Trastuzumab Deruxtecan
Keywords
Antibody-drug Conjugate, Hydroxychloroquine, Advanced Breast Cancer, Metastatic Breast Cancer
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • HydroxychloroquineDrug

    Also called Plaquenil

    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 GovitecanDrug

    Also called IMMU-132, Trodelvy™, GS-0132

    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 DeruxtecanDrug

    Also called DS-8201, Enhertu

    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 groups in NCT06328387
Study groupRoleWhat they receive
Sacituzumab GovitecanOtherSacituzumab 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.
Receives: Drug: Sacituzumab Govitecan
Hydroxychloroquine Combined With Sacituzumab GovitecanExperimentalThe 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.
Receives: Drug: Hydroxychloroquine; Drug: Sacituzumab Govitecan
Trastuzumab DeruxtecanOtherPatients 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.
Receives: Drug: Trastuzumab Deruxtecan
Hydroxychloroquine Combined With Trastuzumab DeruxtecanExperimentalThe 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.
Receives: Drug: Hydroxychloroquine; Drug: Trastuzumab Deruxtecan

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose Limiting Toxicity, DLT

    A dose limiting toxicity（DLT）is defined as any of the following-related adverse event(AE) that occurs during the DLT period, graded according to the NCI Common Terminology Criteria for Adverse Events(CTCAE), Version 5.0

    Measured: 3 weeks

  2. Adverse event, AE

    Any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.

    Measured: 2 years

  3. Objective Response Rate, ORR

    the proportion of patients with a tumor volume reduction of ≥30% and a minimum timeframe according to accepted response evaluation criteria (e.g., RECIST version 1.1 in solid tumors), including cases of complete response (CR) and partial response (PR).

    Measured: 2 years

Secondary outcomes (7)

  1. Progression-Free Survival, PFS

    The time from the beginning of treatment to the progression or death of the patient

    Measured: 2 years

  2. Overall Survival, OS

    The time from the start of randomization to death due to any cause.

    Measured: 4 years

  3. Clinical Benefit Rate, CBR

    Proportion of confirmed complete response, partial response, or stable disease ≥ 24 weeks.

    Measured: 24 weeks after enrollment

  4. Disease Control Rate, DCR

    Proportion of patients with stable or shrinking tumor size--sum of the proportions of complete remission (CR), partial remission (PR) and stable disease (SD).

    Measured: 2 years

  5. The rate of adverse events

    The probability and severity of adverse reactions were analyzed up to 24 weeks after enrollment

    Measured: up to 24 weeks after enrollment

  6. Quality of life scale score, QoL

    The quality of life score of patients during treatment was analyzed(FACT-B). Performance Status Rating (PSR) was demonstrated for the FACT-B total score, which is the result of the following subscale scores: SWB (the Social / family Well-Being subscale) , EWB (the Emotional Well-Being subscale), AC (Additional Concerns subscale), PWB (the Physical Well-Being subscale), FWB (the Functional Well-Being subscale)

    Measured: 1 year

  7. Exploration of biomarkers

    Objective to explore the correlation between biomarkers and the ORR. The biomarkers will be test by nest-generation sequence, which include 520 genes and tumor mutation burden, like ERBB2/TP53/PIK3CA/ERBB4/CCND1 and so on.

    Measured: the first week after the enrollment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Mar 2024
  2. Study start29 Jan 2024
  3. Primary completion1 Feb 2026 (estimated)
  4. Study completion1 Mar 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
The research model consists of four arms： 1. arm A: SG. 2. arm B: HCQ+SG. 3. arm C: T-DXd . 4. arm D: HCQ+T-DXd.
Masking
None (open label)
Enrolment
120 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06328387
Sponsor's protocol ID
SYSKY-2024-064-03
Status last verified
Mar 2024
First submitted
17 Mar 2024
Last updated
25 Mar 2024
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: As personal information of patients is involved, we decided not to share individual participant data of patients.

Publications

  • Fu Z, Li S, Han S, Shi C, Zhang Y. Antibody drug conjugate: the "biological missile" for targeted cancer therapy. Signal Transduct Target Ther. 2022 Mar 22;7(1):93. doi: 10.1038/s41392-022-00947-7.

    PubMed 35318309

  • Hurvitz SA, Hegg R, Chung WP, Im SA, Jacot W, Ganju V, Chiu JWY, Xu B, Hamilton E, Madhusudan S, Iwata H, Altintas S, Henning JW, Curigliano G, Perez-Garcia JM, Kim SB, Petry V, Huang CS, Li W, Frenel JS, Antolin S, Yeo W, Bianchini G, Loi S, Tsurutani J, Egorov A, Liu Y, Cathcart J, Ashfaque S, Cortes J. Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: updated results from DESTINY-Breast03, a randomised, open-label, phase 3 trial. Lancet. 2023 Jan 14;401(10371):105-117. doi: 10.1016/S0140-6736(22)02420-5. Epub 2022 Dec 7.

    PubMed 36495879

  • Chen YF, Xu YY, Shao ZM, Yu KD. Resistance to antibody-drug conjugates in breast cancer: mechanisms and solutions. Cancer Commun (Lond). 2023 Mar;43(3):297-337. doi: 10.1002/cac2.12387. Epub 2022 Nov 10.

    PubMed 36357174

  • Burris HA 3rd, Rugo HS, Vukelja SJ, Vogel CL, Borson RA, Limentani S, Tan-Chiu E, Krop IE, Michaelson RA, Girish S, Amler L, Zheng M, Chu YW, Klencke B, O'Shaughnessy JA. Phase II study of the antibody drug conjugate trastuzumab-DM1 for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer after prior HER2-directed therapy. J Clin Oncol. 2011 Feb 1;29(4):398-405. doi: 10.1200/JCO.2010.29.5865. Epub 2010 Dec 20.

    PubMed 21172893

  • Loganzo F, Tan X, Sung M, Jin G, Myers JS, Melamud E, Wang F, Diesl V, Follettie MT, Musto S, Lam MH, Hu W, Charati MB, Khandke K, Kim KS, Cinque M, Lucas J, Graziani E, Maderna A, O'Donnell CJ, Arndt KT, Gerber HP. Tumor cells chronically treated with a trastuzumab-maytansinoid antibody-drug conjugate develop varied resistance mechanisms but respond to alternate treatments. Mol Cancer Ther. 2015 Apr;14(4):952-63. doi: 10.1158/1535-7163.MCT-14-0862. Epub 2015 Feb 2.

    PubMed 25646013

  • Rios-Luci C, Garcia-Alonso S, Diaz-Rodriguez E, Nadal-Serrano M, Arribas J, Ocana A, Pandiella A. Resistance to the Antibody-Drug Conjugate T-DM1 Is Based in a Reduction in Lysosomal Proteolytic Activity. Cancer Res. 2017 Sep 1;77(17):4639-4651. doi: 10.1158/0008-5472.CAN-16-3127. Epub 2017 Jul 7.

    PubMed 28687619

  • Yu SF, Zheng B, Go M, Lau J, Spencer S, Raab H, Soriano R, Jhunjhunwala S, Cohen R, Caruso M, Polakis P, Flygare J, Polson AG. A Novel Anti-CD22 Anthracycline-Based Antibody-Drug Conjugate (ADC) That Overcomes Resistance to Auristatin-Based ADCs. Clin Cancer Res. 2015 Jul 15;21(14):3298-306. doi: 10.1158/1078-0432.CCR-14-2035. Epub 2015 Apr 3.

    PubMed 25840969

  • Le Joncour V, Martins A, Puhka M, Isola J, Salmikangas M, Laakkonen P, Joensuu H, Barok M. A Novel Anti-HER2 Antibody-Drug Conjugate XMT-1522 for HER2-Positive Breast and Gastric Cancers Resistant to Trastuzumab Emtansine. Mol Cancer Ther. 2019 Oct;18(10):1721-1730. doi: 10.1158/1535-7163.MCT-19-0207. Epub 2019 Jul 10.

    PubMed 31292166

  • Li X, He S, Ma B. Autophagy and autophagy-related proteins in cancer. Mol Cancer. 2020 Jan 22;19(1):12. doi: 10.1186/s12943-020-1138-4.

    PubMed 31969156

  • Mauthe M, Orhon I, Rocchi C, Zhou X, Luhr M, Hijlkema KJ, Coppes RP, Engedal N, Mari M, Reggiori F. Chloroquine inhibits autophagic flux by decreasing autophagosome-lysosome fusion. Autophagy. 2018;14(8):1435-1455. doi: 10.1080/15548627.2018.1474314. Epub 2018 Jul 20.

    PubMed 29940786

  • Yamamoto K, Venida A, Yano J, Biancur DE, Kakiuchi M, Gupta S, Sohn ASW, Mukhopadhyay S, Lin EY, Parker SJ, Banh RS, Paulo JA, Wen KW, Debnath J, Kim GE, Mancias JD, Fearon DT, Perera RM, Kimmelman AC. Autophagy promotes immune evasion of pancreatic cancer by degrading MHC-I. Nature. 2020 May;581(7806):100-105. doi: 10.1038/s41586-020-2229-5. Epub 2020 Apr 22.

    PubMed 32376951

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Hydroxychloroquine, Sacituzumab Govitecan and Trastuzumab Deruxtecan in people with Advanced Breast Cancer and Metastatic Breast Cancer, run by Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 25 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Jianli J Zhao, doctorate (15920589334, zhaojli5@mail.sysu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose Limiting Toxicity, DLT (time frame: 3 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06328387, which also lists 11 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Mar 2024.

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