Pretreatment With HCQ Before Radiotherapy and Chemotherapy in Advanced NPC Patients

Nasopharyngeal Carcinoma Clinical Trial

Official title:

Pretreatment With HCQ Before Radiotherapy and Chemotherapy in Advanced NPC Patients

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06389201
• Other study ID #: 2024HCQ
• Status: Not yet recruiting
• Phase: N/A
• Start date: May 1, 2024
• Est. completion date: December 31, 2026

Study information

• Verified date: April 2024
• Source: Affiliated Hospital of Nantong University
• Contact: Bo You, Doctor
• Phone: +8615851358688
• Email: youbo19891014[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 our attention because of their association with the clinical risk of nasopharyngeal carcinoma (NPC) recurrence, as demonstrated by previous clinical data. In study, we 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.

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.

Our 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 70 Years

Eligibility

Inclusion Criteria:

• Patients are pathologically confirmed cases of NPC. All patients provide informed consent and had not received any cancer therapies prior to the biopsy.

Exclusion Criteria:

• Patients with metastasis before the first treatment.

Related Conditions & MeSH terms

• Nasopharyngeal Carcinoma

Intervention

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

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

Locations

Country	Name	City	State
China	Bo You	Nantong	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
Affiliated Hospital of Nantong University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recurrence and metastasis	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.