Pretreatment With HCQ Before Radiotherapy and Chemotherapy in Advanced NPC Patients

NCT ID: NCT06389201

Last Updated: 2025-02-18

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-08-01
• Study Completion Date: 2034-08-01

Brief Summary

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.

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.

Conditions

Nasopharyngeal Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: EXPERIMENTAL

HCQ

Intervention Type: DRUG

HCQ, 400-600mg, oral tablet, once, one day before chemotherapy and radiotherapy. During therapy, HCQ maintenance dose is 200-400mg daily.

Receive placebo before and during chemotherapy and radiotherapy

Placebos are used one day before chemotherapy and radiotherapy, and during the therapy.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Placebo, oral tablet, once, one day before chemotherapy and radiotherapy. During therapy, placebo maintenance oral tablet once daily.

Interventions

HCQ

HCQ, 400-600mg, oral tablet, once, one day before chemotherapy and radiotherapy. During therapy, HCQ maintenance dose is 200-400mg daily.

Intervention Type: DRUG

Placebo

Placebo, oral tablet, once, one day before chemotherapy and radiotherapy. During therapy, placebo maintenance oral tablet once daily.

Intervention Type: OTHER

Other Intervention Names

Hydroxychloroquine

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

• With metastasis before the first treatment.

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Affiliated Hospital of Nantong University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bo You, Doctor

Role: PRINCIPAL_INVESTIGATOR

Department of Otorhinolaryngology-Head and Neck Surgery, Affiliated Hospital of Nantong University

Locations

Bo You

Nantong, Jiangsu, China

Site Status: RECRUITING

Countries

China

Central Contacts

Bo You, Doctor

Role: CONTACT

youbo19891014@163.com

+8615851358688 ext. +8615851358688

Facility Contacts

Bo You

Role: primary

youbo@ntu.edu.cn

Other Identifiers

2024HCQ

Identifier Type: -

Identifier Source: org_study_id