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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)

Primary Purpose

Nasopharyngeal Carcinoma, Recurrent or Metastatic Nasopharyngeal Carcinoma

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Toripalimab and Anlotinib
Sponsored by
Sun Yat-sen University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Nasopharyngeal Carcinoma

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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;
  • Patients with esophageal and gastric varices, active ulcers, intestinal perforation or intestinal obstruction within 6 months before enrollment;
  • A history of abdominal fistula, digestive tract perforation, intra-abdominal abscess or acute gastrointestinal bleeding within 6 months before enrollment;
  • Multiple factors affecting oral administration and absorption of drugs (e.g., inability to swallow, post-gastrointestinal resection, chronic diarrhea and intestinal obstruction);
  • Overoperation/venous thromboembolism events, NCI CTCAE grade 3 or higher venous thromboembolism within 6 months before enrollment, such as cerebrovascular accident (including temporary ischemic attack), deep venous thrombosis (except for those venous thrombosis caused by venous catheterization due to previous chemotherapy and determined to be cured by the researchers ), pulmonary embolism, etc.;
  • Patients with past and present objective evidence of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-related pneumonia, or severe impairment of lung function;
  • Exacerbation of chronic obstructive pulmonary disease (COPD) or other respiratory disease requiring hospitalization within 28 days before enrollment;
  • Active pulmonary infection and/or acute bacterial or fungal infection requiring intravenous antibiotic treatment within 28 days;
  • Dominant jaundice due to abnormal liver function within 7 days;
  • Renal insufficiency: routine urinalproteinuria > 2+ and confirmed 24 h urinary protein quantification > 1.0g;
  • Minor surgical operations (including catheterization, excluding central venous catheterization via peripheral venipuncture) within 2 days before enrollment;
  • Major surgery within 28 days before enrollment;
  • A potent CYP3A4 inhibitor within one week prior to enrollment, or a potent CYP3A4 inducer within two weeks prior to study participation
  • Long-term unhealed wounds or incomplete fractures;
  • Symptomatic central nervous system metastases (e.g. brain edema, need for hormonal intervention, or brain metastases)
  • The presence of serious or uncontrolled infections;

Sites / Locations

  • Sun Yat-sen Universitiy Cancer Center, Sun Yat-Sen UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Toripalimab and Anlotinib Combination Treatment

Arm Description

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

Outcomes

Primary Outcome Measures

Objective Response rate
Objective Response rate will be determined on the basis of investigator assessments
Disease Control rate
the proportion of patients who had a best response rating of complete response, partial response, or stable disease will be determined on the basis of investigator assessments

Secondary Outcome Measures

Progression Free Survival
The time from the start of treatment to the progression of the tumor or death (due to any cause).
Overall Survival
The time from the start of treatment to time of death (due to any cause).
Complete Response rate
Complete Response rate will be determined on the basis of investigator assessments
Partial Response rate
Partial Response rate will be determined on the basis of investigator assessments
Duration of Response
The time from the first assessment of complete remission or partial remission to progressive disease or death (due to any cause).
Percentage of Participants With Adverse Events
Adverse Events will be determined and graded on the basis of investigator assessments according to NCI CTC AE 5.0

Full Information

First Posted
August 5, 2021
Last Updated
March 23, 2022
Sponsor
Sun Yat-sen University
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1. Study Identification

Unique Protocol Identification Number
NCT04996758
Brief Title
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)
Official Title
Open-Label, Phase Ⅱ Study of 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)
Study Type
Interventional

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Recruiting
Study Start Date
August 1, 2021 (Actual)
Primary Completion Date
August 2023 (Anticipated)
Study Completion Date
August 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sun Yat-sen University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nasopharyngeal Carcinoma, Recurrent or Metastatic Nasopharyngeal Carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
39 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Toripalimab and Anlotinib Combination Treatment
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Toripalimab and Anlotinib
Intervention Description
Toripalimab 240 mg iv.drip d1; Anlotinib 12mg po qd d1-14.
Primary Outcome Measure Information:
Title
Objective Response rate
Description
Objective Response rate will be determined on the basis of investigator assessments
Time Frame
2 years
Title
Disease Control rate
Description
the proportion of patients who had a best response rating of complete response, partial response, or stable disease will be determined on the basis of investigator assessments
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Progression Free Survival
Description
The time from the start of treatment to the progression of the tumor or death (due to any cause).
Time Frame
5 years
Title
Overall Survival
Description
The time from the start of treatment to time of death (due to any cause).
Time Frame
5 years
Title
Complete Response rate
Description
Complete Response rate will be determined on the basis of investigator assessments
Time Frame
2 years
Title
Partial Response rate
Description
Partial Response rate will be determined on the basis of investigator assessments
Time Frame
2 years
Title
Duration of Response
Description
The time from the first assessment of complete remission or partial remission to progressive disease or death (due to any cause).
Time Frame
5 years
Title
Percentage of Participants With Adverse Events
Description
Adverse Events will be determined and graded on the basis of investigator assessments according to NCI CTC AE 5.0
Time Frame
5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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; Patients with esophageal and gastric varices, active ulcers, intestinal perforation or intestinal obstruction within 6 months before enrollment; A history of abdominal fistula, digestive tract perforation, intra-abdominal abscess or acute gastrointestinal bleeding within 6 months before enrollment; Multiple factors affecting oral administration and absorption of drugs (e.g., inability to swallow, post-gastrointestinal resection, chronic diarrhea and intestinal obstruction); Overoperation/venous thromboembolism events, NCI CTCAE grade 3 or higher venous thromboembolism within 6 months before enrollment, such as cerebrovascular accident (including temporary ischemic attack), deep venous thrombosis (except for those venous thrombosis caused by venous catheterization due to previous chemotherapy and determined to be cured by the researchers ), pulmonary embolism, etc.; Patients with past and present objective evidence of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-related pneumonia, or severe impairment of lung function; Exacerbation of chronic obstructive pulmonary disease (COPD) or other respiratory disease requiring hospitalization within 28 days before enrollment; Active pulmonary infection and/or acute bacterial or fungal infection requiring intravenous antibiotic treatment within 28 days; Dominant jaundice due to abnormal liver function within 7 days; Renal insufficiency: routine urinalproteinuria > 2+ and confirmed 24 h urinary protein quantification > 1.0g; Minor surgical operations (including catheterization, excluding central venous catheterization via peripheral venipuncture) within 2 days before enrollment; Major surgery within 28 days before enrollment; A potent CYP3A4 inhibitor within one week prior to enrollment, or a potent CYP3A4 inducer within two weeks prior to study participation Long-term unhealed wounds or incomplete fractures; Symptomatic central nervous system metastases (e.g. brain edema, need for hormonal intervention, or brain metastases) The presence of serious or uncontrolled infections;
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Qingqing Cai
Phone
0086-20-87342823
Email
caiqq@sysucc.org.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Qingqing Cai
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Qingqing Cai
Organizational Affiliation
Sun Yat-sen Universitiy Cancer Center, Sun Yat-Sen University,
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sun Yat-sen Universitiy Cancer Center, Sun Yat-Sen University
City
Guangzhou
ZIP/Postal Code
510030
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Qingqing Cai
Phone
18565617120
Email
18565617120@163.com

12. IPD Sharing Statement

Learn more about this trial

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)

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