Toripalimab and Anlotinib Combination Treatment in Patients With Recurrent or Metastatic Nasopharyngeal Carcinoma After Failure of at Least One Line of Platinum-Based Chemotherapy (TORAL)

NCT04996758 | Completed Phase 2

• 1 other identifier: B2021-055
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This phase 2 trial studies toripalimab and anlotinib combination treatment in patients with recurrent or metastatic nasopharyngeal carcinoma after failure of at least one line of platinum-based chemotherapy

Conditions

Nasopharyngeal Carcinoma; Recurrent or Metastatic Nasopharyngeal Carcinoma

Outcome Measures

Primary Outcomes (1)

• Objective Response rate

  Objective Response rate will be determined on the basis of investigator assessments

  2 years

Secondary Outcomes (7)

• Disease Control rate

  2 years

• Progression Free Survival

  5 years

• Overall Survival

  5 years

• Complete Response rate

  2 years

• Partial Response rate

  2 years

Study Arms (1)

Toripalimab and Anlotinib Combination Treatment

EXPERIMENTAL

Patients receive toripalimab at a dose of 240 mg on day 1 and anlotinib at a dose of 12 mg before breakfast for once-daily on days 1-14. Treatment cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity

Drug: Toripalimab and Anlotinib

Interventions

Toripalimab and Anlotinib DRUG

Toripalimab 240 mg iv.drip d1; Anlotinib 12mg po qd d1-14.

Toripalimab and Anlotinib Combination Treatment

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed undifferentiated non-keratinizing carcinoma
• Patients suffered failure of at least one line of platinum-based chemotherapy. The definition of treatment failure: progression during or after chemotherapy for recurrence/metastasis; progression after concurrent chemoradiotherapy within 6 months. Withdrawal of treatment due to drug intolerances is excluded ;
• Without other malignancy;
• Male or female, 18-70 years;
• Eastern Cooperative Oncology Group (ECOG) of 0-2;
• Life expectancy ≥ 3 months;
• Women of childbearing age must obtain the negative result of a pregnancy test (serum or urine) , and they were willing to use reliable methods of contraception during the trial;
• At least one evaluable lesion；
• Laboratory tests meet the following standards:
• Blood routine: White blood cell count (WBC) ≥3.0×10 9 /L, neutrophil count (ANC) ≥1.5×10 9 /L, platelet count (PLT) ≥75×10 9 /L, hemoglobin (HGB) 90 g/L or higher; Liver function: total bilirubin ≤1.5 times the upper limit of normal (ULN); glutamic-oxalacetic transaminase (AST) and alanine transaminase (ALT) ≤2.5 times ULN, AST and ALT ≤2.5 times ULN for the patients with liver metastases; Alkaline phosphatase ≤5 times ULN; Renal function: Serum creatinine (Cr) ≤1.5 times ULN; Creatinine clearance ≥60mL/min; Urine routine: urine protein \<2+ ;baseline urine protein ≥2+ and 24 hours urine protein \< 1g ; Coagulation: International normalized ratio (INR) and activated partial thrombin time (APTT) ≤1.5 times ULN; Albumin ≥28g/L Thyroid stimulating hormone (TSH)≤1 times ULN (free triiodothyrosine \[FT3\] or free thyroxine \[FT4\] ≤1 times ULN can be included)
• No serious cardiopulmonary dysfunction;
• The informed consent has been signed.
• Ability to comply with test requirements

You may not qualify if:

• A known allergy to any of the drugs in the study;
• Pregnant or breastfeeding women;
• Participated in clinical trials of other drugs within 4 weeks prior to study initiation;
• Previous treatment with bevacizumab or VEGFR-family small molecule tyrosine kinase inhibitors (e.g., famitinib, sorafenib, Sunitinib, regofinib, Apatinib, Anlotinib, fuquinitinib) ;
• Recurrent nasopharyngeal lesions after radiotherapy and who received secondary radiotherapy;
• Palliative radiotherapy for symptom control within 28 days before enrollment;
• Immunosuppressive treatment with immunosuppressive agent, systemic or absorbable topical hormone therapy ( prednisone or other therapeutic hormone at the dose greater than 10mg/ day) within 2 weeks before enrollment;
• Active autoimmune diseases, with the necessity of systemic treatment (hormone replacement therapy is not considered as a systemic treatment, such as type 1 diabetes) over the past two years; autoimmune diseases that did not require systemic treatment in the past two years;
• A history of immunodeficiency, including acquired/congenital immunodeficiency disorders, a history of organ transplantation;
• Vaccinated with live vaccine (inactivated virus vaccine for seasonal influenza is allowed) within 4 weeks before enrollment;
• Invasion of important vessels (e.g. surrounding internal carotid artery/vein) on MRI; tumor with a high risk of affecting vital blood vessels during treatment and causing fatal hemorrhage, which is determined by investigators;
• A history of severe bleeding and any bleeding event with a severity rating of 3 or higher in the NCI CTCAE within 4 weeks prior to screening;
• Abnormal coagulation (INR \> 2.0, PT \> 16s) and bleeding tendency (the INR must be within the normal range without anticoagulants during14 days prior to signing the informed consent); patients treated with anticoagulants or vitamin K antagonists such as warfarin, heparin, or their analogests; low-dose warfarin (1 mg orally, once daily) or low-dose aspirin (up to 100 mg daily) for preventive purposes, provided that the international normalized ratio of prothrombin time (INR) is ≤ 1.5;
• Unstable angina and/or congestive heart failure or vascular disease with the need of hospital treatment; other cardiac damage that may affect the drug safety;
• Patients with hypertension that is not well controlled with antihypertensive medication (systolic \> 140mmHg, diastolic \> 90 mmHg); patients is taking a combination of two or more antihypertensive drugs; Cardiovascular disease with clinical significance， such as cerebrovascular accident (≤ 6 months before randomization), myocardial infarction (≤ 6 months before randomization), unstable angina, congestive heart failure of NYHA grade II or higher, or severe arrhythmias that cannot be controlled with drugs or have a potential impact on experimental treatments;

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-sen Universitiy Cancer Center, Sun Yat-Sen University

Guangzhou, 510030, China

Location

Related Publications (1)

• Zhang Y, Zou Q, Zhao B, Su N, Li Z, Wang X, Liu P, Tian X, Fang X, Cai J, Li L, Liu Y, Xia Y, Cai Q. Toripalimab plus anlotinib in patients with recurrent or metastatic nasopharyngeal carcinoma: A multicenter, single-arm phase 2 trial (TORAL). Cell Rep Med. 2024 Dec 17;5(12):101833. doi: 10.1016/j.xcrm.2024.101833. Epub 2024 Nov 29.

  PMID: 39615484 DERIVED

MeSH Terms

Conditions

Nasopharyngeal Carcinoma; Recurrence

Interventions

toripalimab; anlotinib

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Nasopharyngeal Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Qingqing Cai

  Sun Yat-sen Universitiy Cancer Center, Sun Yat-Sen University,

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief physician

Study Record Dates

• First Submitted: August 5, 2021
• First Posted: August 9, 2021
• Study Start: October 30, 2021
• Primary Completion: September 30, 2023
• Study Completion: December 1, 2024
• Last Updated: December 12, 2024

Record last verified: 2024-12

Locations

CN (1)