Combining Camrelizumab with Stereotactic Body Radiotherapy for Nasopharyngeal Carcinoma

A Phase II Randomized Trial of Camrelizumab With Stereotactic Body Radiotherapy Versus Camrelizumab Alone in Patients With Recurrent or Metastatic Nasopharyngeal Carcinoma

This study is testing if combining a new immune therapy called camrelizumab with targeted radiation can help people with recurrent or metastatic nasopharyngeal cancer feel better and fight their disease more effectively.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 39 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Chongqing University Cancer Hospital (other)
• Drugs / interventions: Camrelizumab, chemotherapy, immunotherapy, radiation, prednisone
• Locations: 3 sites (Chongqing, Chongqing Municipality and 2 other locations)
• Trial ID: NCT04830267 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness of camrelizumab, an immune checkpoint inhibitor, in combination with stereotactic body radiotherapy for patients with recurrent or metastatic nasopharyngeal carcinoma. Eligible participants will be randomly assigned to receive either standard treatment with camrelizumab alone or the experimental combination of camrelizumab and stereotactic body radiotherapy. The goal is to enhance the immune response against cancer cells while utilizing targeted radiation therapy. The study will take place across three hospitals in Chongqing and Sichuan, China.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with histologically confirmed metastatic or recurrent nasopharyngeal carcinoma and specific measurable lesions.

Not a fit: Patients with non-recurrent nasopharyngeal carcinoma or those who do not meet the eligibility criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve treatment outcomes for patients with recurrent or metastatic nasopharyngeal carcinoma.

How similar studies have performed: Other studies have shown promising results with similar combinations of immunotherapy and radiotherapy, suggesting potential for success in this approach.

Eligibility criteria

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.

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.

Where this trial is running

Chongqing, Chongqing Municipality and 2 other locations

• Chongqing University Cancer Hospital — Chongqing, Chongqing Municipality, China (RECRUITING)
• Chongqing University Three Gorges Hospital — Wanzhou, Chongqing Municipality, China (RECRUITING)
• The Affiliated Hospital of Southwest Medical University — Luzhou, Sichuan, China (RECRUITING)

Study contacts

• Principal investigator: Ying Wang, Ph.D, M.D. — Chongqing University Cancer Hospital
• Study coordinator: Jiangdong Sui, Ph.D, M.D.

Conditions: Nasopharyngeal Carcinoma, Camrelizumab, Stereotactic body radiotherapy, R/M NPC, Best overall response