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The Efficacy of Camrelizumab Plus Stereotactic Body Radiotherapy in R/M NPC

Phase 2
Recruiting
Conditions
Nasopharyngeal Carcinoma
Interventions
Drug: Camrelizumab
Radiation: Stereotactic body radiotherapy
Registration Number
NCT04830267
Lead Sponsor
Chongqing University Cancer Hospital
Brief Summary

Camrelizumab is an antibody targeting programmed death receptor 1 (PD-1) and its ligand programmed death-ligand 1 (PD- L1) that is designed to boost the immune system. It does this by allowing immune cells to fight the cancer. Stereotactic body radiotherapy is a potential immunostimulatory therapy that may amplify antitumor response when combined with camrelizumab.

Detailed Description

All eligible patients from 3 hospitals will be equally randomized between the 2 following treatment groups:

Standard treatment group: Camrelizumab 200mg IV every 2 weeks. Experimental group: Stereotactic body radiotherapy 27Gy/3F and Camrelizumab 200mg IV every 2 weeks.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
39
Inclusion Criteria
  1. Signed Written Informed Consent

  2. Subjects must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines.

  3. Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other study obligations.

  4. Target Population:

    Males and females ≥ 18 years of age Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2. Histologically confirmed metastatic or recurrent nasopharyngeal carcinoma.

  5. Subjects must have at least two lesions:

    At least one lesion must be safely amenable to irradiation. This can be a lesion that was previously irradiated as long as prior radiation was at least 6 months prior to projected first fraction of SBRT and as long as reirradiation dose constraints are being met.

    A separate, not-to-be-irradiated lesion measurable by CT or MRI per RECIST 1.1 criteria.

  6. The peripheral blood EBV DNA copy number can be obtained.

  7. Prior palliative or curative radiotherapy must be completed at least 14 days prior to randomization.

  8. Immunosuppressive doses of systemic medication, such as steroids or absorbed topical steroids (doses >10mg/day prednisone or equivalent) must be discontinued at least 14 days prior to Camrelizumab administration.

  9. Screening laboratory values must meet the following criteria (using CTCAE v4.0) and should be obtained within 28 days prior to randomization:

    WBC ≥ 2 K/microliter Neutrophils ≥ 1.5 K/microliter Platelets ≥ 100 K/microliter Hemoglobin ≥ 9.0 g/deciliter Serum Creatinine ≤ 1.5 x ULN or creatinine clearance > 40ml/min using the Cockcroft-Gault formula.

    Female CrCl = (140 - age in years) x weight in kg x 0.85 72 x serum creatinine in mg/dL Male CrCl = (140 - age in years) x weight in kg x 1.00 72 x serum creatinine in mg/dL AST/ALT ≤ 3 x ULN Total bilirubin <1.5 x ULN (except subjects with Gilbert Syndrome who can have total bilirubin <3.0 mg/deciliter).

    Subjects must have a resting baseline O2 saturation by pulse oximetry of >=92% at rest.

  10. Reproductive Status:

Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 28 days prior to randomization.

Women must not be breastfeeding Women of childbearing potential must agree to follow instructions for method(s) of contraception from time of enrollment for the duration of treatment with Camrelizumab plus 5 half- lives plus 30 days for a total of 23 weeks post treatment completion.

Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Men receiving Camrelizumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product.

Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile as well as azoospermic men do not require contraception.

Azoospermic males and women of childbearing potential who are continuously not heterosexually active are exempt from contraceptive requirements. However, they still must have a pregnancy test.

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Exclusion Criteria
  1. Target Disease Exceptions:

    Active brain metastases (untreated brain metastases or growth on imaging as defined below) or leptomeningeal disease are not allowed. Subjects with brain metastases are eligible if these have been treated and there is no MRI (or CT if MRI contraindicated) evidence of progression for at least 8 weeks after treatment for these metastases is complete and within 28 days prior to first study treatment.

  2. Medical History and Concurrent Diseases:

    Any medical disorder that, in the opinion of the investigator, might increase the risk associated with study participation or interferes with the interpretation of study results.

    Prior active malignancy within the previous 3 years except for locally curable cancers such as basal or squamous skin cancer, superficial bladder, low risk prostate cancer, breast, or cervix cancer. If other prior malignancy was active within prior 3 years, enrollment requires approval of a principal investigator.

    Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration should be excluded. Inhaled or topical steroids and adrenal replacement doses >10mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.

  3. Physical and Laboratory Test Findings:

    Positive test for hepatitis B virus surface antigen or hepatitis C virus ribonucleic acid indicating acute or chronic infection.

    Known history of testing positive for HIV or known AIDS. Any grade 4 laboratory abnormalities. Allergies and Adverse Drug Reaction History of allergy to Camrelizumab components History of severe hypersensitivity reaction to any monoclonal antibody.

  4. Prohibited or Restricted Treatments:

The following medications are prohibited during the study:

Immunosuppressive agents (except to treat a drug-related adverse event). Systemic corticosteroids > 10 mg daily prednisone equivalent save for exclusion outlined in the below paragraphs.

Any concurrent chemotherapy, hormonal therapy, immunotherapy, or investigational agents for treatment of cancer.

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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Stereotactic body radiotherapy plus CamrelizumabStereotactic body radiotherapyStereotactic body radiotherapy 27Gy/3F and Camrelizumab 200mg IV every 2 weeks
Stereotactic body radiotherapy plus CamrelizumabCamrelizumabStereotactic body radiotherapy 27Gy/3F and Camrelizumab 200mg IV every 2 weeks
Camrelizumab aloneCamrelizumabCamrelizumab 200mg IV every 2 weeks
Primary Outcome Measures
NameTimeMethod
Best overall response (BOR)Time Frame: 96 weeks

As determined by the investigator using RECIST 1.1 criteria between patients receiving Camrelizumab and stereotactic body radiotherapy and those receiving Camrelizumab alone. BOR rate is defined as the number of patients randomized to a given arm with a best overall response of complete response (CR) or partial response (PR) of non-irradiated lesions divided by the total number of patients randomized to the given arm. In order to ascertain this endpoint, efforts will be made so that patients will be followed for 96 weeks or until progression of disease (and treatment cessation), whichever comes first. At each time-point, subjects should have CT/MR of neck, chest, abdomen, and pelvis with contrast.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (3)

Chongqing University Cancer Hospital

🇨🇳

Chongqing, Chongqing, China

Chongqing University Three Gorges Hospital

🇨🇳

Wanzhou, Chongqing, China

The Affiliated Hospital of Southwest Medical University

🇨🇳

Luzhou, Sichuan, China

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