Pretreatment With HCQ Before Radiotherapy and Chemotherapy in Advanced NPC Patients

February 14, 2025 updated by: Affiliated Hospital of Nantong University

Dormant cancer cells that survive anti-cancer therapy can lead to cancer recurrence and disseminated metastases that prove fatal in most cases. Recently, specific dormant polyploid giant cancer cells (PGCC) have drawn the investigators' attention because of their association with the clinical risk of nasopharyngeal carcinoma (NPC) recurrence, as demonstrated by previous clinical data. In study, the investigators report the biological properties of PGCC, and reveal that autophagy is a critical mechanism of PGCC induction. Moreover, pharmacological inhibition of autophagy greatly impaired PGCC formation, significantly suppressing metastasis and improving survival in a mouse model. Mechanistically, chemotherapeutic drugs partly damaged mitochondria, and activated autophagy to promote PGCC formation. High numbers of PGCCs correlated with shorter recurrence time and worse survival outcomes in NPC patients. Collectively, these findings suggest a therapeutic approach of targeting dormant PGCCs in cancer.

Pretreatment with an autophagy inhibitor (HCQ) before chemotherapy and radiotherapy could prevent formation of therapy-induced dormant polyploid giant cancer cells, thereby reducing recurrence and metastasis of nasopharyngeal carcinoma.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Although the majority of patients with nasopharyngeal carcinoma (NPC) do not present with overt metastases at diagnosis, a significant number succumb to disseminated disease years after the successful treatment of the primary tumor. Thus, late NPC recurrence may be the result of rare and elusive dormant cancer cells hiding in specialized niches being reactivated by specific signals. The concept of cancer dormancy has been described for the most common solid and hematological cancers; however, the dormant cancer cells in NPC remain largely uncharacterized.

Although many factors contribute toward cancer cell dormancy, recent studies have demonstrated that cancer therapy can induce cellular dormancy. Indeed, therapy-induced dormancy has been shown to lead to durable proliferation arrest, resulting in the formation of polyploid giant cancer cells (PGCCs), which are a unique sub-population of cancer cells that contribute toward the heterogeneity of solid tumors. Unlike regular-sized diploid cancer cells, PGCCs display distinct morphological features, including a large cytoplasmic area and a high genomic content contained within a single highly enlarged nucleus or multiple nuclei. Despite being present in low numbers, the frequency of PGCCs increases markedly after exposure to hypoxia and therapeutic interventions such as radiotherapy and chemotherapies.

The investigators' findings, which used a highly relevant clinical orthotopic model of imageable NPC and clinical data, suggest that autophagy inhibition (HCQ) prevents therapy-induced dormant PGCC formation and thereby prevents NPC metastasis.

Study Type

Interventional

Enrollment (Estimated)

30

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Jiangsu
      • Nantong, Jiangsu, China, 226000

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Clinical diagnosis of NPC.
  • Have not received any cancer therapies
  • Must provide informed consent

Exclusion Criteria:

  • With metastasis before the first treatment.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Pretreatment with an autophagy inhibitor (HCQ) before chemotherapy and radiotherapy
Hydroxychloroquine (HCQ), is used one day before chemotherapy and radiotherapy, 400-600mg, oral tablet, once. During chemotherapy and radiotherapy, HCQ maintenance dose is 200-400mg daily.
Drug: HCQ
HCQ, 400-600mg, oral tablet, once, one day before chemotherapy and radiotherapy. During therapy, HCQ maintenance dose is 200-400mg daily.
Other Names:
  • Hydroxychloroquine
Placebo Comparator: Receive placebo before and during chemotherapy and radiotherapy
Placebos are used one day before chemotherapy and radiotherapy, and during the therapy.
Other: Placebo
Placebo, oral tablet, once, one day before chemotherapy and radiotherapy. During therapy, placebo maintenance oral tablet once daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Recurrence and metastasis
Time Frame: Five to Ten years.
After the patients are diagnosed and treated, CT scans is used semi-annually to determine the progression, recurrence and metastasis of tumor.
Five to Ten years.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Affiliated Hospital of Nantong University

Investigators

  • Principal Investigator: Bo You, Doctor, Department of Otorhinolaryngology-Head and Neck Surgery, Affiliated Hospital of Nantong University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 1, 2024

Primary Completion (Estimated)

August 1, 2029

Study Completion (Estimated)

August 1, 2034

Study Registration Dates

First Submitted

April 25, 2024

First Submitted That Met QC Criteria

April 25, 2024

First Posted (Actual)

April 29, 2024

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

February 14, 2025

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2024HCQ

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Study protocol, statistical analysis plan, informed consent form, clinical study report, and analytic code will be shared to other researchers.

IPD Sharing Time Frame

Two years after this clinical trial finished.

IPD Sharing Access Criteria

Researchers must clearly state the purpose of their study and ensure it aligns with the scientific objectives of the data sharing initiative. A detailed research plan, including research design, data analysis methods, and expected results, should be provided to ensure the data is used in a reasonable and effective manner. Additionally, researchers must outline data security and privacy protection measures to ensure the safe storage, transmission, and use of the data in compliance with relevant regulations and policies.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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