Sintilimab and Nimotuzumab Combined With Chemotherapy for the Treatment of R/M HNSCC. (Carpp-1)

A Multicenter, Single-arm Study of Sintilimab and Nimotuzumab Combined With Chemotherapy for the Treatment of Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma

This clinical study is designed as a prospective, open-label, single arm, multicenter study to evaluate the clinical efficacy and safety of Sintilimab and Nimotuzumab in combination with chemotherapy in patients with newly diagnosed recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). The main endpoint is progression free survival (PFS); the secondary endpoint are objective response rate (ORR), disease control rate (DCR), overall survival (OS) and safety.

Study Overview

• Status: Not yet recruiting
• Conditions: Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Nimotuzumab; Drug: Sintilimab; Drug: Chemotherapy drug

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Juying Zhou; Phone Number: 13962142066; Email: ci49802974@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Voluntary and sign a consent form;
2. Age 18-75 years old, gender unlimited;
3. Histology or imaging diagnosed as R/M HNSCC, patients haven't received any anti-tumor treatment for R/M HNSCC; Including oral cavity cancer, oropharyngeal cancer, hypopharyngeal cancer, laryngeal cancer, nasopharyngeal cancer, paranasal sinus and nasal cavity cancer, etc.;
4. PD-L1 immunohistochemistry and EGFR immunohistochemistry should be performed on tumor tissue samples;
5. according to the efficacy evaluation criteria for solid tumors (RECIST version 1.1), at least one measurable lesion;
6. Not received any previous systemic antitumor therapy for R/M HNSCC. Subjects who had previously received adjuvant/neoadjuvant chemotherapy, or had received radical chemoradiotherapy for advanced disease, were allowed to be enrolled in this study if the interval between disease progression or recurrence and the end of the last treatment (including chemotherapy /EGFR monoclonal antibody /EGFR-TKI/ antiangiogenic agents) was beyond 6 months. Radiotherapy for individual recurrent and/or metastatic lesions cannot be ruled out.
7. ECOG PS 0-2
8. Expected survival time ≥ 3 months;
9. Enough organ function, the participants need to satisfy the following laboratory indicators: 1) nearly 14 days without the use of granulocyte colony stimulating factor, absolute neutrophil count ≥ 1.5 × 109/L; 2) Platelets ≥100×109/L in the case of no blood transfusion in the last 14 days; 3) Hemoglobin ≥9g/dL (90g/L) or≥5.6 mmol/L in the absence of blood transfusion or erythropoietin treatment within the last 14 days; 4) total bilirubin ≤1.5×upper limit of normal (ULN); 5) Aspartate aminotransferase (AST) /alanine aminotransferase (ALT) ≤2.5×ULN, or AST/ALT≤5×ULN in subjects with liver metastasis; 6) Serum creatinine ≤1.5×ULN and creatinine clearance (calculated by Cockcroft-Gault formula) ≥60 mL /min; 7) Good coagulant function; 8) Thyroid function is normal; 9) Myocardial enzyme spectrum is normal;
10. For females of reproductive age, a pregnancy test with negative results should be performed within 3 days prior to receiving the first dosing (cycle 1 day 1);
11. To avoid pregnancy, an effective contraception should used for female patients.

Exclusion Criteria:

1. squamous cell carcinoma of skin;
2. Patients with uncured malignancies other than R/M HNSCC diagnosed within 5 years prior to initial administration;
3. Participating in other clinical studies, or receiving other investigational drugs or using investigational devices within 4 weeks prior to first dosing;
4. Have received any other anti-tumor treatment for R/M HNSCC, including PD-1 inhibitor, PD-L1 inhibitor, CD137 inhibitor, EGFR monoclonal antibody, EGFR-TKI, anti-angiogenic drugs, etc.;
5. Major surgery or chemotherapy was performed within 4 weeks prior to enrollment;
6. Have received immunomodulatory drugs (including thymosin, interferon, interleukin);
7. Active autoimmune disease with systemic therapy (such as glucocorticoids or immunosuppressants) within 2 years prior to initial administration. Alternative therapy (e.g. thyroxine, insulin, etc.) is not considered systemic therapy.
8. Have received systemic glucocorticoid therapy within 7 days prior to enrollment; Note: Physiological dose of glucocorticoids (≤10 mg/ day of prednisone or equivalent drugs) is allowed.
9. Allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation;
10. Allergic to the study drugs;
11. Have not fully recovered from toxicity and/or complications caused by any intervention prior to enrollment;
12. History of human immunodeficiency virus (HIV) infection;
13. Untreated active hepatitis B; Note: Hepatitis B patients who meet the following criteria can also be enrolled: 1) HBV DNA<1000 copies /ml (200 IU/ml) prior to enrollment; 2) anti-HBcAg(+), HBsAg (-), anti-HBsAg (-), and HBV DNA(-), prophylactic anti-HBV therapy is not required, but virus reactivation needs to be closely monitored;
14. Active HCV infection;
15. Live vaccine was given within 30 days;
16. Pregnant or lactating women;
17. Any serious or uncontrollable systemic disease;
18. Other reasons that are not suitable to participate in this study according to the researcher's judgment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: single arm	Drug: Nimotuzumab; Nimotuzumab, 400mg, intravenously every 3 weeks, for at least 18 weeks; Drug: Sintilimab; Sintilimab, 200mg, intravenously every 3 weeks, for at least 18 weeks; Drug: Chemotherapy drug; Chemotherapy drugs were selected by the investigator, every 3 weeks, for 18 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression Free Survival	Up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	objective response rate	Up to 12 months
DCR	disease control rate	Up to 12 months
OS	overall survival	Up to 12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarker	To evaluate the relationship between tumor biomarkers (including but not limited to EGFR or PD-L1 expression, TILs, TMB, HPV status, P16 expression, etc.) and prognosis.	Up to 12 months

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Soochow University
• Collaborators: Biotech Pharmaceutical Co., Ltd.; Cinda Biopharmaceutical (Suzhou) Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2021
• Primary Completion (Anticipated): November 30, 2021
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: May 6, 2021
• First Submitted That Met QC Criteria: May 6, 2021
• First Posted (Actual): May 12, 2021

Study Record Updates

• Last Update Posted (Actual): May 12, 2021
• Last Update Submitted That Met QC Criteria: May 6, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Neoplasms, Squamous Cell; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Antineoplastic Agents; Antineoplastic Agents, Immunological; Nimotuzumab
• Other Study ID Numbers: BPL-IST-H&N-20210318

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No