Sintilimab Combined With Chemotherapy and SBRT in Limited Metastatic Head and Neck Squamous Cell Carcinoma (LM-HNSCC) (LM-HNSCC)

November 16, 2021 updated by: Jun-Lin Yi, MD

Phase II Clinical Study of Sintilimab Combined With Platinum-based Chemotherapy and SBRT in the First-line Treatment of Limited Metastatic Head and Neck Squamous Cell Carcinoma

To evaluate the safety and efficacy of combination of Sintilimab and SBRT on the basis of platinum-containing chemotherapy as the first-line treatment of limited metastatic head and neck squamous cell carcinoma (LM-HNSCC).

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

For patients with LM-HNSCC, the conventional first-line treatment is EXTREME regimen dominated systemic therapy. In the recent era, immunotherapy has emerged to be the paramount issue for cancer treatment. A series of high-quality clinical studies demonstrated that immunotherapy (such as PD1 inhibitor) with or without chemotherapy (depending on CPS status) offered significant survival benefits to patients with recurrent or metastatic (R/M) HNSCC and the toxicities were well tolerated, whereas the PFS was still dismal. SBRT is associated with initiating release of tumor antigens, promoting DC activation, activating APCs, priming CD8+ CTLs, leading to the potential of abscopal effect. Therefore, we hypothesized that adding SBRT to Sintilimab (a PD1 inhibitor) and platinum-containing chemotherapy as the first-line treatment may improve the PFS for limited metastatic head and neck squamous cell carcinoma (LM-HNSCC).

Study Type

Interventional

Enrollment (Anticipated)

50

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
      • Beijing, China, 100021
        • Cancer hospital, Chinese Academy of Medical Sciences

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Sign written informed consent before implementing any trial-related procedures;
  • Male or female, age ≥18 years old;
  • Histologically confirmed head and neck squamous cell carcinoma, which was diagnosed as initial stage IVC/M1(synchronous metastatic disease) according to the 8th edition of UICC/AJCC or previously treated head and neck tumor with newly occurred metachronous metastatic disease ;
  • Pathological diagnosis of metastasis is not mandatory, but the clinical diagnosis needs to receive consent of MDT;
  • The number of metastases is 1-10;
  • PD-L1 expression is positive, CPS≥1;
  • According to the evaluation criteria for the efficacy of solid tumors (RECIST version 1.1), at least one metastatic lesion is radiologically measurable;
  • Newly-diagnosed HNSCC who has not received any treatment previously or HNSCC who has been diagnosed metastases for the first time after treatment;
  • For patients who have received platinum-containing chemotherapy in the past, the interval between the new metastasis and the end of the last chemotherapy administration is at least 6 months;
  • After a comprehensive radiological examination, at least one extracranial metastatic lesion with a maximum diameter of ≤ 5cm (which can be treated with SBRT);
  • ECOG score 0-1 points;
  • Sufficient organ function, subjects need to meet the following laboratory indicators: In the past 14 days without using granulocyte colony stimulating factor, the absolute value of neutrophils (ANC) ≥ 1.5x109/L. In the case of no blood transfusion in the past 14 days, platelets ≥100×109/L. In the past 14 days without blood transfusion or using erythropoietin, hemoglobin>9g/dL；Total bilirubin≤1.5×upper limit of normal (ULN); or total bilirubin>ULN but direct bilirubin≤ULN；Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are within ≤2.5×ULN;Serum creatinine ≤1.5×ULN and creatinine clearance rate (calculated by Cockcroft-Gault formula) ≥60 ml/min; Good coagulation function, defined as International Normalized Ratio (INR) or Prothrombin Time (PT) ≤ 1.5 times ULN;Normal thyroid function is defined as thyroid stimulating hormone (TSH) within the normal range. If the baseline TSH is outside the normal range, subjects whose total T3 (or FT3) and FT4 are within the normal range can also be included in the group;The myocardial enzyme spectrum is within the normal range (if the investigator comprehensively judges that the simple laboratory abnormality is not of clinical significance, it is also allowed to be included);
  • Expected survival> 1 year;
  • At least one lesion is RECIST 1.1 assessable lesion;
  • No previous PD1 or PD-L1 inhibitor treatment history;
  • Without comorbidities that needs treatment of immunodepressant;
  • Male subjects and women of childbearing age must have contraception within 24 weeks from the start of the study to the last time of using the drug.

Exclusion Criteria:

  • The primary site is squamous cell carcinoma of the nasopharynx or skin cancer.
  • The number of metastases>10;
  • Patients who have been diagnosed with other malignant tumors within 5 years before the first administration and have not been cured (excluding radically cured skin basal cell carcinoma, skin squamous epithelial carcinoma, and/or radically resected carcinoma in situ);
  • Currently participating in interventional clinical research treatment, or received other research drugs or used research devices within 4 weeks before the first administration;
  • Have received the following therapies in the past: anti-PD-1, anti-PD-L1 or anti-PD-L2 drugs or for another stimulating or synergistic inhibition of T cell receptors (for example, CTLA-4, OX-40, CD137) drug;
  • Received systemic treatment with anti-tumor indications Chinese patent medicines or immunomodulatory drugs (including thymosin, interferon, interleukin, except for local use to control pleural fluid) within 2 weeks before the first administration;
  • An active autoimmune disease that requires systemic treatment (such as the use of disease-relieving drugs, glucocorticoids, or immunosuppressive agents) occurred within 2 years before the first administration. Alternative therapies (such as thyroxine, insulin, or physiological glucocorticoids for adrenal or pituitary insufficiency, etc.) are not considered systemic treatments;
  • Administration of systemic steroid (not include nasal spray, inhalation or other local approach) within 7 days before the first administration of Sintilimab or any other ways of immunosuppression;
  • Receiving Xenografts or allogeneic hematopoietic stem cell transplantation in the past;
  • Allergic to component of research drugs or adjacent;
  • HIV infection;
  • Untreated active hepatitis B (HBsAg positive and HBV-DNA copy number larger than upper limit of threshold);
  • Untreated active hepatitis C (HCV antibody positive and HCV-RNA larger than upper limit of threshold);
  • Inoculation with live vaccine within 30 days before the first administration of Sintilimab;
  • Women patients in the pregnancy or lactation period;
  • With severe or uncontrollable comorbidity.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Single arm
Sintilimab combined with platinum-based chemotherapy and SBRT
Drug: Sintilimab
Sintilimab: 200mg, administered by intravenous infusion on the first day of each cycle, one cycle every 3 weeks (Q3W), with the maximum cycle of 17. Suspension of Sintilimab administration: patients's request, disease progression, researcher-evaluated SAE
Other Names:
  • Tyvyt®
Radiation: SBRT

At least one metastatic lesion is suitable for SBRT. If applicable, all metastatic lesions were allowed to be irradiated.

Recommended dose: BED ≥ 80Gy. Dose fractionation is determined as per physician's discretion, generally depending on the location of irradiated lesion and the distance to surrounding OARs.

Timing of SBRT: After completing at least 2 platinum-containing chemotherapy plus sintilimab treatments, SBRT can be started after assessing that there is no AE ≥ G2.

Other Names:
  • SABR
Drug: Platinum based chemotherapy
Platinum based single or doublet chemotherapy, one cycle every 3 weeks (Q3W), 4-6 cycles.
Other Names:
  • chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival time (PFS)
Time Frame: Up to 2 years
PFS is defined as the duration from the starting date of per-protocol treatment to first progression of disease, death or closure of study.
Up to 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival time (OS)
Time Frame: Up to 2 years
OS was calculated from the starting date of per-protocol treatment to death from any cause.
Up to 2 years
Objective response rate (ORR)
Time Frame: Up to 1 years
CR + PR rate according to the RECIST version 1.1 guidelines.
Up to 1 years
Disease control rate (DCR)
Time Frame: Up to 1 years
CR + PR + SD rate according to the RECIST version 1.1 guidelines.
Up to 1 years
Duration of disease response (DOR)
Time Frame: Up to 2 years
The time from the date of first identification of response (CR or PR) to progression/death (P/D).
Up to 2 years
Time to progression of initial lesions (TPIL)
Time Frame: Up to 2 years
The time from the first date of per-protocol treatment to progression of baseline lesions or death.
Up to 2 years
Time to progression of new lesions (TPNL)
Time Frame: Up to 2 years
The time from the first date of per-protocol treatment to the appearance of new lesion of tumor or death.
Up to 2 years
Time to progression of non-irradiated lesions (TPNRL)
Time Frame: Up to 2 years
Duration from the first date of per-protocol treatment to the specific progression of non-irradiated lesion or death.
Up to 2 years
Adverse events
Time Frame: Up to 2 years
Adverse event assessment according to NCI CTCAE 5.0, including AE, TEAE, SAE and irAE.
Up to 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Jun-Lin Yi, MD

Investigators

  • Principal Investigator: Junlin Yi, MD, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

December 1, 2021

Primary Completion (Anticipated)

December 1, 2023

Study Completion (Anticipated)

December 1, 2024

Study Registration Dates

First Submitted

November 16, 2021

First Submitted That Met QC Criteria

November 16, 2021

First Posted (Actual)

November 29, 2021

Study Record Updates

Last Update Posted (Actual)

November 29, 2021

Last Update Submitted That Met QC Criteria

November 16, 2021

Last Verified

November 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCC3100

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Head and Neck Squamous Cell Carcinoma

Clinical Trials on Sintilimab

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Nigeria

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe