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Nasopharyngeal CarcinomaPhase 2NCT04548271

Camrelizumab Combined With Apatinib in Patients With PD-1 Antagonists Resistant Recurrent/Metastatic Nasopharyngeal Carcinoma

A Phase 2 study testing Camrelizumab and Apatinib in people with Nasopharyngeal Carcinoma, run by Sun Yat-sen University at 1 site in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

The purpose of this study is to explore the efficacy and safety of combination of Apatinib and Camrelizumab regimen in treating recurrent or metastatic nasopharyngeal carcinoma patients who were resistant to PD-1 antagonists. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Nasopharyngeal Carcinoma
What is being tested?
Camrelizumab and Apatinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
1 siteChina
Study dates
Sep 2020to Oct 2023
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically or cytologically confirmed with recurrent or metastatic nasopharyngeal carcinoma which is not amenable to curative treatment with surgery and/or radiation therapy.
  • Age ≥ 18 years and ≤ 75 years, both genders.
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.
  • Life expectancy of at least 3 months.
  • Have failed for first-line platinum-based chemotherapy.
  • Have failed for prior treatment with PD-1 antagonists +/- chemotherapy.
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  • Patients must have at least 1 lesion that is measurable using RECIST v1.1 criteria.
  • Patients must have adequate organ function (without blood transfusion, without growth factor or blood components support within 14 days before enrollment) as determined by:
  • Absolute neutrophil count (ANC) ≥1.5×109/L; Platelet count ≥ 75×109/L; Hemoglobin ≥ 9 g/dL; serum total bilirubin (TBIL) ≤1.5 times the upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×upper limit of normal (ULN), (for subjects with liver metastases, TBIL ≤3×ULN ; ALT and AST≤5×ULN); Creatinine ≤1.5×ULN or creatinine clearance rate≥50 ml/min (Cockcroft-Gault formula); serum albumin ≥28 g/L; Thyroid-stimulating hormone (TSH) levels ≤1×ULN (however, patients with free Triiodothyronine [FT3] or free Thyroxine [FT4] levels ≤1× ULN may be enrolled); INR, APTT≤1.5 x ULN.
  • All women with fertility potential must undergo a urine or serum pregnancy test during screening and the results are negative.
  • Written informed consent.

Who cannot join

  • Known history of hypersensitivity to any components of the Camrelizumab formulation, or other monoclonal antibody.
  • Prior therapy with tyrosine kinase-inhibitor agent targeting at VEGFR.
  • There was a history of severe bleeding, and any bleeding events with a serious grade of 3 or more in CTCAE5.0 occurred within 4 weeks before screening.
  • Before treatment, MRI showed that the tumor may have invaded important blood vessels (such as enclosing the internal carotid artery / vein), nasopharyngeal necrosis, or researchers have determined that the tumor is highly likely to invade important blood vessels and cause fatal massive bleeding during treatment.
  • Patients with abnormal blood coagulation and bleeding tendency (14 days before signing informed consent: INR is within the normal range without anticoagulant); patients treated with anticoagulants or vitamin K antagonists such as warfarin, heparin or their analogues. On the premise that the INR < 1.5, low-dose warfarin (1mg orally, once a day) or low-dose aspirin (daily dose not more than 100mg) is allowed for preventive purposes.
  • Arteriovenous thrombosis occurred within one year before screening, such as cerebrovascular accident (including temporary ischemic attack), deep venous thrombosis (except venous thrombosis caused by intravenous catheterization due to early chemotherapy) and pulmonary embolism.
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  • Patients with hypertension who cannot be well controlled by antihypertensive therapy (systolic blood pressure ≥ 140mmHg, diastolic blood pressure ≥ 90mmHg); patients with a history of hypertensive crisis or hypertensive encephalopathy.
  • Proteinuria ≥ (++) or 24 hours total urine protein > 1.0 g.
  • Received any CYP3A4 inhibitor within 2 weeks before the first administration.
  • Have a history of Crohn's disease, ulcerative colitis, and chronic diarrhea.
  • Have a history of gastrointestinal perforation or fistula.
  • Any factors that affect the oral drug.
  • Prior malignancy active within the previous 5 years except for locally curable cancers that have been apparently cured, such as basal cell skin cancer or carcinoma in situ of the cervix.
  • Join another clinical study at the same time, received any research drug within 4 weeks before the first administration of the drug.
  • Patients with any active autoimmune disease or a documented history of autoimmune disease such as pneumonia, colitis, hepatitis, nephritis, hyperthyroidism or hypothyroidism;
  • Concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic or absorbable topical corticosteroids. Doses > 10 mg/day prednisone or equivalent are prohibited within 2 weeks before study drug administration.
  • History of immunodeficiency including seropositivity for human immunodeficiency virus (HIV), or other acquired or congenital immune-deficient disease.
  • Be known to have active tuberculosis.
  • Hepatitis B virus (HBV) >2000 IU/ml or DNA ≥ 1×10^4/ml; or hepatitis C virus (HCV) RNA ≥ 1×10^3/ml).
  • Has an active infection requiring systemic therapy.
  • Has known active central nervous system metastases.
  • Severe, uncontrolled angiocardiopathy (heart failure > class II NYHA, unstable angina, myocardial infarction within past 1 year, supraventricular or ventricular arrhythmia which need medical intervention, or QT interval male ≥ 450 ms, female ≥ 470 ms.).
  • Have been vaccinated with anti-tumor vaccines or have been vaccinated with live vaccines within 4 weeks before screening.
  • Pregnant or nursing.
  • Underlying medical condition that, in the Investigator's opinion, would increase the risks of study drug administration or obscure the interpretation of toxicity determination or adverse events.

Trial locations and contacts

1 site in 1 country.

Haiqiang Mai contact

86-20-87343380

maihq@sysucc.org.cn

Linquan Tang contact

86-20-87343380

tanglq@sysucc.org.cn

China1 site

  • Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center

    Guangzhou, Guangdong, 510060

Other trials in China

About this study

Official title: Efficacy and Safety of Camrelizumab Combined With Apatinib in Patients With PD-1 Antagonists Resistant Recurrent/Metastatic Nasopharyngeal Carcinoma: a Single-center, Single-arm, Phase 2 Trail

The purpose of this study is to explore the efficacy and safety of combination of Apatinib and Camrelizumab regimen in treating recurrent or metastatic nasopharyngeal carcinoma patients who were resistant to PD-1 antagonists.

Read the detailed description

Currently, there is still no uniform treatment regimen in treating recurrent or metastatic nasopharyngeal carcinoma patients who failed to first-line platinum-based chemotherapy. Anti-PD-1 monoclonal antibody showed efficacy and safety in previous studies, however, the efficacy of immunotherapy alone was limited. Immunotherapy combined with other treatment regimens for recurrent or metastatic nasopharyngeal carcinoma is a strategy that needs to be urgently explored. Vascular endothelial growth factor (VEGF) is an important target in the treatment of nasopharyngeal carcinoma. Apatinib, a small-molecule tyrosine kinase inhibitor selectively inhibits vascular endothelial growth factor receptor 2 (VEGFR-2), has shown strong clinical utility. Previous clinical studies have confirmed that apatinib shows antitumor activity and tolerable toxicity in recurrent or metastatic nasopharyngeal carcinoma. Tumor vascular normalization and immune reprogramming interact synergistically and could enter a mutually reinforcing virtuous cycle by improving tumor microenvironment. The current national comprehensive cancer network (NCCN) guidelines also recommend Nivolumab and Pembrolizumab as second-line treatment for recurrent or metastatic nasopharyngeal carcinoma. More and more evidences show that immunotherapy combined with anti-angiogenesis therapy has a synergistic effect, and Camrelizumab combined with apatinib has achieved initial effect in solid tumors. Based on this, this study aims to evaluate the efficacy and safety of Camrelizumab combined with apatinib in the patients with recurrent or metastatic nasopharyngeal carcinoma who failed to first-line anti-PD-1 monoclonal antibody, to provide new evidence for individualized comprehensive treatment in nasopharyngeal carcinoma.

Being tested
Camrelizumab, Apatinib
Medical subject headings
Nasopharyngeal Carcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CamrelizumabDrug

    Also called SHR-1210

    Anti-PD-1 targeted immunotherapy

  • ApatinibDrug

    Also called Apatinib Mesylate

    A small-molecule vascular endothelial growth factors receptor (VEGFR) tyrosine kinase inhibitor

Study groups in NCT04548271
Study groupRoleWhat they receive
Camrelizumab+ApatinibExperimentalPatients with recurrent or metastatic nasopharyngeal carcinoma who failed to first-line platinum-based chemotherapy and had prior treatment with PD-1 antagonists. Every patients will receive apatinib 250mg orally every day starting 14 days prior to Camrelizumab. Then apatinib 250mg orally every day and Camrelizumab 200mg iv every 3 weeks until disease progression or intolerance of side effects.
Receives: Drug: Camrelizumab; Drug: Apatinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective response rate

    An objective response is defined as either a confirmed CR or a PR, as determined by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST1.1) from the National Cancer Institute (NCI)

    Measured: 2 years

Secondary outcomes (7)

  1. Disease control rate

    A disease control rate is defined as either a confirmed CR or a PR or a SD, as determined by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST1.1) from the National Cancer Institute (NCI).

    Measured: 2 years

  2. Duration of response

    Defined from date of first confirmed CR or a PR to date of first documentation of progression or death due to any cause, as determined by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST1.1) from the National Cancer Institute (NCI).

    Measured: 2 years

  3. Progression-free survival rate

    Defined from date of registration to date of first documentation of progression or death due to any cause.

    Measured: 2 years

  4. Overall survival rate

    Defined from date of registration to date of first documentation of death from any cause or censored at the date of the last follow-up.

    Measured: 2 years

  5. Incidence rate of adverse events (AEs)

    Analysis of acute and late adverse events (AEs) are evaluated. Numbers of patients of treatment-related adverse events (acute toxicity) as assessed by CTCAE v5.0.

    Measured: 2 years

  6. PD-L1 expression on tumor and immune cells

    The efficacy of the combination of Camrelizumab and apatinib as measured by objective response, will be described in patients according to PD-L1 positive and PD-L1 negative.

    Measured: 2 years

  7. VEGFR-2 expression in tumor

    The impact of VEGFR-2 on efficacy of the combination of Camrelizumab and apatinib will be explored.

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Sep 2020
  2. Study startSep 2020 (estimated)
  3. Primary completionOct 2022 (estimated)
  4. Study completionOct 2023 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
25 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04548271
Sponsor's protocol ID
B2020-187
Status last verified
Sep 2020
First submitted
7 Sep 2020
Last updated
14 Sep 2020
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Zhang L, Huang Y, Hong S, Yang Y, Yu G, Jia J, Peng P, Wu X, Lin Q, Xi X, Peng J, Xu M, Chen D, Lu X, Wang R, Cao X, Chen X, Lin Z, Xiong J, Lin Q, Xie C, Li Z, Pan J, Li J, Wu S, Lian Y, Yang Q, Zhao C. Gemcitabine plus cisplatin versus fluorouracil plus cisplatin in recurrent or metastatic nasopharyngeal carcinoma: a multicentre, randomised, open-label, phase 3 trial. Lancet. 2016 Oct 15;388(10054):1883-1892. doi: 10.1016/S0140-6736(16)31388-5. Epub 2016 Aug 23.

    PubMed 27567279

  • Hsu C, Lee SH, Ejadi S, Even C, Cohen RB, Le Tourneau C, Mehnert JM, Algazi A, van Brummelen EMJ, Saraf S, Thanigaimani P, Cheng JD, Hansen AR. Safety and Antitumor Activity of Pembrolizumab in Patients With Programmed Death-Ligand 1-Positive Nasopharyngeal Carcinoma: Results of the KEYNOTE-028 Study. J Clin Oncol. 2017 Dec 20;35(36):4050-4056. doi: 10.1200/JCO.2017.73.3675. Epub 2017 Aug 24.

    PubMed 28837405

  • Ma BBY, Lim WT, Goh BC, Hui EP, Lo KW, Pettinger A, Foster NR, Riess JW, Agulnik M, Chang AYC, Chopra A, Kish JA, Chung CH, Adkins DR, Cullen KJ, Gitlitz BJ, Lim DW, To KF, Chan KCA, Lo YMD, King AD, Erlichman C, Yin J, Costello BA, Chan ATC. Antitumor Activity of Nivolumab in Recurrent and Metastatic Nasopharyngeal Carcinoma: An International, Multicenter Study of the Mayo Clinic Phase 2 Consortium (NCI-9742). J Clin Oncol. 2018 May 10;36(14):1412-1418. doi: 10.1200/JCO.2017.77.0388. Epub 2018 Mar 27.

    PubMed 29584545

  • Fang W, Yang Y, Ma Y, Hong S, Lin L, He X, Xiong J, Li P, Zhao H, Huang Y, Zhang Y, Chen L, Zhou N, Zhao Y, Hou X, Yang Q, Zhang L. Camrelizumab (SHR-1210) alone or in combination with gemcitabine plus cisplatin for nasopharyngeal carcinoma: results from two single-arm, phase 1 trials. Lancet Oncol. 2018 Oct;19(10):1338-1350. doi: 10.1016/S1470-2045(18)30495-9. Epub 2018 Sep 10.

    PubMed 30213452

  • Li J, Qin S, Xu J, Xiong J, Wu C, Bai Y, Liu W, Tong J, Liu Y, Xu R, Wang Z, Wang Q, Ouyang X, Yang Y, Ba Y, Liang J, Lin X, Luo D, Zheng R, Wang X, Sun G, Wang L, Zheng L, Guo H, Wu J, Xu N, Yang J, Zhang H, Cheng Y, Wang N, Chen L, Fan Z, Sun P, Yu H. Randomized, Double-Blind, Placebo-Controlled Phase III Trial of Apatinib in Patients With Chemotherapy-Refractory Advanced or Metastatic Adenocarcinoma of the Stomach or Gastroesophageal Junction. J Clin Oncol. 2016 May 1;34(13):1448-54. doi: 10.1200/JCO.2015.63.5995. Epub 2016 Feb 16.

    PubMed 26884585

  • Lan CY, Wang Y, Xiong Y, Li JD, Shen JX, Li YF, Zheng M, Zhang YN, Feng YL, Liu Q, Huang HQ, Huang X. Apatinib combined with oral etoposide in patients with platinum-resistant or platinum-refractory ovarian cancer (AEROC): a phase 2, single-arm, prospective study. Lancet Oncol. 2018 Sep;19(9):1239-1246. doi: 10.1016/S1470-2045(18)30349-8. Epub 2018 Aug 3.

    PubMed 30082170

  • Reck M, Mok TSK, Nishio M, Jotte RM, Cappuzzo F, Orlandi F, Stroyakovskiy D, Nogami N, Rodriguez-Abreu D, Moro-Sibilot D, Thomas CA, Barlesi F, Finley G, Lee A, Coleman S, Deng Y, Kowanetz M, Shankar G, Lin W, Socinski MA; IMpower150 Study Group. Atezolizumab plus bevacizumab and chemotherapy in non-small-cell lung cancer (IMpower150): key subgroup analyses of patients with EGFR mutations or baseline liver metastases in a randomised, open-label phase 3 trial. Lancet Respir Med. 2019 May;7(5):387-401. doi: 10.1016/S2213-2600(19)30084-0. Epub 2019 Mar 25.

    PubMed 30922878

  • Xu J, Zhang Y, Jia R, Yue C, Chang L, Liu R, Zhang G, Zhao C, Zhang Y, Chen C, Wang Y, Yi X, Hu Z, Zou J, Wang Q. Anti-PD-1 Antibody SHR-1210 Combined with Apatinib for Advanced Hepatocellular Carcinoma, Gastric, or Esophagogastric Junction Cancer: An Open-label, Dose Escalation and Expansion Study. Clin Cancer Res. 2019 Jan 15;25(2):515-523. doi: 10.1158/1078-0432.CCR-18-2484. Epub 2018 Oct 22.

    PubMed 30348638

  • Yuan L, Jia GD, Lv XF, Xie SY, Guo SS, Lin DF, Liu LT, Luo DH, Li YF, Deng SW, Guo L, Zeng MS, Cai XY, Liu SL, Sun XS, Li XY, Li SC, Chen QY, Tang LQ, Mai HQ. Camrelizumab combined with apatinib in patients with first-line platinum-resistant or PD-1 inhibitor resistant recurrent/metastatic nasopharyngeal carcinoma: a single-arm, phase 2 trial. Nat Commun. 2023 Aug 14;14(1):4893. doi: 10.1038/s41467-023-40402-x.

    PubMed 37580352

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Camrelizumab and Apatinib in people with Nasopharyngeal Carcinoma, run by Sun Yat-sen University at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 14 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Haiqiang Mai (86-20-87343380, maihq@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective response rate (time frame: 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04548271, which also lists 9 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Sep 2020.

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