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

NCT05136768 | Unknown Phase 2

• 1 other identifier: NCC3100
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Head and Neck Squamous Cell Carcinoma; Metastases; Immunotherapy; Stereotactic Body Radiotherapy

Outcome Measures

Primary Outcomes (1)

• Progression-free survival time (PFS)

  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 Outcomes (8)

• Overall survival time (OS)

  Up to 2 years

• Objective response rate (ORR)

  Up to 1 years

• Disease control rate (DCR)

  Up to 1 years

• Duration of disease response (DOR)

  Up to 2 years

• Time to progression of initial lesions (TPIL)

  Up to 2 years

Study Arms (1)

Single arm

EXPERIMENTAL

Sintilimab combined with platinum-based chemotherapy and SBRT

Drug: Sintilimab; Radiation: SBRT; Drug: Platinum based chemotherapy

Interventions

Sintilimab DRUG

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

Also known as: Tyvyt®

Single arm

SBRT RADIATION

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.

Also known as: SABR

Single arm

Platinum based chemotherapy DRUG

Platinum based single or doublet chemotherapy, one cycle every 3 weeks (Q3W), 4-6 cycles.

Also known as: chemotherapy

Single arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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;

Sponsors & Collaborators

• Jun-Lin Yi, MD: lead

Study Sites (1)

Cancer hospital, Chinese Academy of Medical Sciences

Beijing, 100021, China

Location

Related Publications (3)

• Bahig H, Aubin F, Stagg J, Gologan O, Ballivy O, Bissada E, Nguyen-Tan FP, Soulieres D, Guertin L, Filion E, Christopoulos A, Lambert L, Tehfe M, Ayad T, Charpentier D, Jamal R, Wong P. Phase I/II trial of Durvalumab plus Tremelimumab and stereotactic body radiotherapy for metastatic head and neck carcinoma. BMC Cancer. 2019 Jan 14;19(1):68. doi: 10.1186/s12885-019-5266-4.

  PMID: 30642290 BACKGROUND

• Burtness B, Harrington KJ, Greil R, Soulieres D, Tahara M, de Castro G Jr, Psyrri A, Baste N, Neupane P, Bratland A, Fuereder T, Hughes BGM, Mesia R, Ngamphaiboon N, Rordorf T, Wan Ishak WZ, Hong RL, Gonzalez Mendoza R, Roy A, Zhang Y, Gumuscu B, Cheng JD, Jin F, Rischin D; KEYNOTE-048 Investigators. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Lancet. 2019 Nov 23;394(10212):1915-1928. doi: 10.1016/S0140-6736(19)32591-7. Epub 2019 Nov 1.

  PMID: 31679945 BACKGROUND

• McBride S, Sherman E, Tsai CJ, Baxi S, Aghalar J, Eng J, Zhi WI, McFarland D, Michel LS, Young R, Lefkowitz R, Spielsinger D, Zhang Z, Flynn J, Dunn L, Ho A, Riaz N, Pfister D, Lee N. Randomized Phase II Trial of Nivolumab With Stereotactic Body Radiotherapy Versus Nivolumab Alone in Metastatic Head and Neck Squamous Cell Carcinoma. J Clin Oncol. 2021 Jan 1;39(1):30-37. doi: 10.1200/JCO.20.00290. Epub 2020 Aug 21.

  PMID: 32822275 BACKGROUND

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Neoplasm Metastasis

Interventions

sintilimab; Platinum Compounds; Drug Therapy

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Inorganic Chemicals; Therapeutics

Study Officials

• Junlin Yi, MD

  Cancer Institute and Hospital, Chinese Academy of Medical Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Junlin Yi, MD

CONTACT

86-10-87788792; yijunlin1969@163.com

Jingbo Wang, MD

CONTACT

86-10-87788995; wangjingbo303@yahoo.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: UNKNOWN
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Vice director of Dept. Radiotherapy

Model Details: Prospective, single center, single arm, phase II clinical study

Study Record Dates

• First Submitted: November 16, 2021
• First Posted: November 29, 2021
• Study Start: December 1, 2021
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2024
• Last Updated: November 29, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)