Immunotherapy and Chemotherapy in Unresectable Recurrent Loco-regionally Advanced Nasopharyngeal Carcinoma (RETICULA-NPC)

Fudan University

Status and phase: Enrolling; Phase 2

Conditions: Chemotherapy Effect; Recurrent Nasopharyngeal Carcinoma; Unresectable Nasopharyngeal Carcinoma; Stereotactic Body Radiation Therapy (SBRT); Immunotherapy

Treatments: Drug: Tislelizumab

Study type: Interventional

Funder types: Other

Identifiers

NCT04921995

2021052-1

Details and patient eligibility

About

This is an open-label, multi-center, phase II trial to evaluate the safety and efficacy of postponing or omitting re-irradiation after systemic therapy with tislelizumab and chemotherapy in patients with unresectable recurrent loco-regionally advanced nasopharyngeal carcinoma. Patients who did not respond to or progressed on another ICI are allowed to receive tislelizumab rechallenge as a subgroup.

Full description

High dose reirradiation is usually recommended for unresectable recurrent loco-regionally advanced nasopharyngeal carcinoma. However, it potentially adds to the RT-related severe toxicities and deaths. This trial aims to investigate the feasibility of postponing or even omitting re-irradiation based on effective first-line systemic therapy with tislelizumab and chemotherapy. For patients that progressed after exposure to another PD-1 antibody,tislelizumab rechallenge is accepted as a second subgroup.In this trial, all patients will receive chemotherapy (on doctors' recommendation) and PD-1 antibody (tislelizumab 200mg every three weeks). Patients with no response to the systemic therapy will receive salvage low dose re-irradiation delivered by SBRT, while those who showed complete or partial response will continue maintenance therapy until progression, death or intolerable toxicity, and reirradiation will be postponed or omitted.

Enrollment: 40 estimated patients

Sex: All

Ages: 15 to 90 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Diagnosed as local recurrence ± regional recurrence after ≥1 year of radical treatment;
2. Not suitable for surgery;
3. Clinical stage rT3-4N0-2 (rII-IVa, AJCC/UICC 8th);or residual disease afer surgery.
4. ECOG score 0-1;
5. No prior treatment to rNPC, such as radiotherapy, chemotherapy, immunotherapy or biotherapy;
6. No contraindications to immunotherapy or chemoradiotherapy;
7. Adequate marrow function: WBC count ≥ 3×10E9/L, NE count ≥ 1.5×10E9/L, HGB ≥ 90g/L, PLT count ≥ 100×10E9/L;
8. Adequate liver function: ALT/AST ≤ 2.5×ULN, TBIL ≤ 2.0×ULN;
9. Adequate renal function: BUN/CRE ≤ 1.5×ULN or endogenous creatinine clearance ≥ 60ml/min (Cockcroft-Gault formula);
10. Take effective contraceptions during and two months after treatment;
11. Patients must be informed of the investigational nature of this study and give written informed consent.

Exclusion criteria

1. Have local necrosis in recurrent lesions, estimated with bleeding risk;
2. Unexplained fever > 38.5 ℃, except for tumor fever;
3. Treated with ≥ 5 days antibiotics one month before enrollment;
4. Have active autoimmune disease (e.g., uveitis, enteritis, hepatitis, hypophysitis, nephritis, vasculitis, hyperthyroidism, and asthma requiring bronchodilator therapy);
5. Have a known history of human immunodeficiency virus (HIV), active Hepatitis B (HBV-DNA ≥10E3copiers/ml) or hepatitis C virus (HCV) antibody positive;
6. Have ≥G3 late toxicities, except for skin, subcutaneous tissue or mucosa;
7. Have New York Heart Association (NYHA) class 3 or 4, unstable angina, myocardial -infarction within 1 year, or clinically meaningful arrhythmia that requires treatment;
8. Have known allergy to large molecule protein products or any compound of study therapy;
9. Pregnant or breastfeeding;
10. Prior malignancy except adequately treated non-melanoma skin cancer, in situ cervical cancer, and papillary thyroid carcinoma;
11. Any other condition, including mental illness or domestic/social factors, deemed by the investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interferes with the interpretation of the results.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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40 participants in 1 patient group

Experimental

Experimental group

Description:

Main group: Patients will be given first line tislelizumab plus investigator's choice chemotherapy, with re-irradiation postponed or omitted. Subgroup: For patients that progressed after exposure to another PD-1 antibody, tislelizumab rechallenge combined with either low dose SBRT or low dose gemcitabine and metronomic capecitabine is accepted as a second subgroup.

Treatment:

Drug: Tislelizumab