Pretreatment With HCQ Before Radiotherapy and Chemotherapy in Advanced NPC Patients

Trial Title: Pretreatment With HCQ Before Radiotherapy and Chemotherapy in Advanced NPC Patients

NCT ID: NCT06389201

Condition: Nasopharyngeal Carcinoma

Conditions: Official terms:
Nasopharyngeal Carcinoma
Hydroxychloroquine

Conditions: Keywords:
autophagy
tumor dormancy
nasopharyngeal carcinoma
recurrence
metastasis

Study type: Interventional

Study phase: N/A

Overall status: Not yet recruiting

Study design:

Allocation: Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: Single (Participant)

Intervention:

Intervention type: Drug
Intervention name: HCQ
Description: HCQ, 400-600mg, oral tablet, once, one day before chemotherapy and radiotherapy. During therapy, HCQ maintenance dose is 200-400mg daily.
Arm group label: Pretreatment with an autophagy inhibitor (HCQ) before chemotherapy and radiotherapy

Other name: Hydroxychloroquine

Intervention type: Other
Intervention name: Placebo
Description: Placebo, oral tablet, once, one day before chemotherapy and radiotherapy. During therapy, placebo maintenance oral tablet once daily.
Arm group label: Receive placebo before and during chemotherapy and radiotherapy

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.

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. 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.

Criteria for eligibility:
Criteria:
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.

Gender: All

Minimum age: 20 Years

Maximum age: 70 Years

Healthy volunteers: No

Locations:

Facility:
Name: Bo You

Address:
City: Nantong
Zip: 226000
Country: China

Start date: May 1, 2024

Completion date: December 31, 2026

Lead sponsor:
Agency: Affiliated Hospital of Nantong University
Agency class: Other

Source: Affiliated Hospital of Nantong University

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06389201