Sintilimab in Cancer of Unknown Primary

A Phase 2 Clinical Trial Evaluating the Efficacy and Safety of Sintilimab for Advanced Rare Cancers (SiARa Cancer Study) - Cancer of Unknown Primary (SiARa-CUP)

NCT05024968•M.D. Anderson Cancer Center

View on ClinicalTrials.gov

Summary

This is a Phase 2 clinical trial evaluating the efficacy and safety of sintilimab in subjects with CUP. Up to 45 subjects with CUP will be enrolled. Subjects will be treated with sintilimab at 200 mg via intravenous (IV) administration on Cycle 1 Day 1. The treatment will repeat every 3 weeks until progressive disease (PD), intolerable toxicity, initiation of new anti-tumor therapy, withdrawal of consent, lost to follow-up, death, completion of therapy, or any other investigator-determined reasons for treatment discontinuation (whichever occurs first). Treatment will continue for a maximum period of 24 months (starting from the first dose). During the trial, tumor imaging evaluation will be initially performed once every 9 weeks (± 7 days) and will be based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. After the completion or discontinuation of the study treatment, safety follow-up and survival follow-up will be performed. Considering the rareness of the disease, the patient accrual rate is expected to be approximately 2 patients per month. The total study duration is expected to be between 24-27 months with 6-month follow up.

Detailed Description

Primary Objectives: * To evaluate the safety and efficacy of sintilimab in subjects with CUP Secondary Objectives: * To evaluate the overall objective response rate (ORR) (investigator assessed), disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), overall survival (OS) and Quality of Life (QOL) on sintilimab in subjects with CUP Exploratory Objectives: * To evaluate the correlation between biomarkers in tumor tissue and efficacy, including but not restricted to PD-L1 expression level, transcriptome sequencing, single-cell sequencing, and multicolor immunohistochemistry (IHC) analyses; * To evaluate the correlation between biomarkers in peripheral blood and drug efficacy, including but not restricted to soluble PD-L1, circulating tumor DNA (ctDNA), and cytokine analyses.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•1. Has histopathologically confirmed unresectable, locally advanced, recurrent or metastatic CUP. Patients must have undergone standard work-up to attempt to identify the primary tumor prior to enrollment.
•2. Is refractory or intolerant to at least one line of systemic chemotherapy. Patient ineligible for cytotoxic chemotherapy due to contraindications will be eligible.
•3. Has an ECOG PS of 0 - 2.
•4. Must be unsuitable for definitive treatment, such as definitive chemoradiotherapy and/or surgery. For subjects who have received (neo)adjuvant or definitive chemotherapy/chemoradiotherapy, time from the completion of last treatment to disease recurrence must be \> 3 months.
•5. Is able to provide archival or fresh tissues for correlative analysis with obtainable results.
•6. Has at least one measurable lesion as per RECIST v1.1.
•7. Has adequate organ and bone marrow functions, as defined below:
•* Complete blood count: absolute neutrophil count (ANC) ≥ 1.0 × 109/L, platelet (PLT) count ≥ 75 × 109/L, hemoglobin (HGB) ≥ 9.0 g/dL. Note: Subjects cannot receive blood transfusion, erythropoietin (EPO), or Granulocyte-colony stimulating factor (GSF) within 7 days prior to the blood collection.
•* Hepatic function: total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN in subjects without hepatic metastasis; TBIL ≤ 1.5 × ULN, ALT and AST ≤ 5 × ULN in subjects with hepatic metastasis.
•Exception: Patients with known Gilbert disease: serum bilirubin level ≤ 3 × ULN.
+7 more criteria

Exclusion Criteria

•1. Has received treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug that specifically targets T-cell co-stimulation or immune checkpoint pathways.
•2. Is enrolled in another interventional clinical study. Current enrollment in an observational study (non-interventional) or in the follow-up phase of an interventional study is allowed.
•3. Has received palliative therapy for a local lesion within 2 weeks prior to the first dose.
•4. Has received systemic treatment with Chinese traditional medicines with anti-cancer indications or immunomodulators (including thymosins, interferons, and interleukins) within 2 weeks prior to the first dose of study treatment.
•5. Has received systemic immunosuppressants within 2 weeks. Allowed are local use of glucocorticoids administered by nasal, inhaled, or other routes, and systemic glucocorticoids at physiological doses (no more than 10 mg/day of prednisone or equivalents), or glucocorticoids to prevent allergies to contrast media.
•6. Has received a live attenuated vaccine within 4 weeks prior to the first dose of study treatment or is scheduled to receive live attenuated vaccine during the study period.
•Note: Seasonal inactivated influenza virus vaccines within 4 weeks prior to the first dose of study treatment are permitted, but attenuated influenza vaccines are not.
•7. Has undergone major surgery (craniotomy, thoracotomy, or laparotomy) within 4 weeks prior to the first dose of study treatment or is scheduled to receive major surgery during the course of the trial.
•8. Has any toxicity (excluding alopecia, events that are not clinically significant, or asymptomatic laboratory abnormalities) due to prior anti-tumor therapy that has not yet resolved to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 grade 0 or 1 prior to the first dose of study treatment.
•9. Has known symptomatic central nervous system (CNS) metastasis or carcinomatous meningitis. Subjects with brain metastases who have received prior treatment can be enrolled if the disease is stable (no imaging evidence of PD for at least 4 weeks prior to the first dose of study treatment), there is no evidence of new brain metastases or progression of the existing metastatic lesion(s) upon repeated imaging, and corticosteroids have not been required for at least 14 days prior to the first dose of study treatment. Patients with carcinomatous meningitis are ineligible, regardless of whether the disease is clinically stable or not.
+26 more criteria

Locations (1)

M D Anderson Cancer Center

Houston, Texas, United States

Key Dates

Start Date

August 26, 2021

Primary Completion Date

April 3, 2025

Completion Date

April 3, 2025

Last Updated

February 25, 2026

Enrollment

ACTUAL participants

Conditions

Cancer of Unknown Primary Site

Interventions

Sintilimab

DRUG

A Phase II Randomized Study Comparing the Efficacy and Safety of Targeted Therapy or Cancer Immunotherapy Versus Platinum-Based Chemotherapy in Patients With Cancer of Unknown Primary Site

NCT03498521

Cancer of Unknown Primary Site

View study

UNKNOWNPHASE2

Nivolumab/Ipilimumab in Second Line CUP-syndrome

NCT04131621

Cancer of Unknown Primary Site

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: February 25, 2026Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

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