Cancer of Unknown Primary SitePhase 2NCT05024968
Sintilimab in Cancer of Unknown Primary
A Phase 2 study testing Sintilimab in people with Cancer of Unknown Primary Site, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer of Unknown Primary Site
- What is being tested?
- Sintilimab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Aug 2021to 3 Apr 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- Is refractory or intolerant to at least one line of systemic chemotherapy. Patient ineligible for cytotoxic chemotherapy due to contraindications will be eligible.
- Has an ECOG PS of 0 - 2.
- 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.
- Is able to provide archival or fresh tissues for correlative analysis with obtainable results.
- Has at least one measurable lesion as per RECIST v1.1.
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- 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.
- Renal function: urine protein < 2+ from random sample or < 1 g from 24-hour urine collection, and creatinine clearance rate (CrCl) ≥ 30 mL/min by Cockcroft-Gault formula:
- Female: CrCl=((140-age)×weight(kg)×0.85)/(72×serum creatinine(mg/dL))
- Male: CrCl=((140-age)×weight(kg)×1.00)/(72×serum creatinine(mg/dL))
- Adequate coagulation function, defined as international normalized ratio (INR) ≤ 1.5 or prothrombin time (PT) ≤ 1.5 × ULN; if the subject is receiving anticoagulant therapy, the results of coagulation tests need to be within the acceptable range for anticoagulants.
- Is expected to survive ≥ 12 weeks.
- Subject (female subjects of childbearing age or male subjects whose partners are of childbearing age) must take effective contraceptive measures during the entire course of the trial and until 180 days after the last dose (see Section 4.3).
- Is able to sign the informed consent form (ICF) and is able to comply with the scheduled follow-up visits and related procedures required in the protocol.
Who cannot join
- 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.
- 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.
- Has received palliative therapy for a local lesion within 2 weeks prior to the first dose.
- 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.
- 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.
- 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.
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- 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.
- 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.
- 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.
- 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.
- Has bone metastases and is at risk for paraplegia.
- Has known active autoimmune disease requiring treatment or a previous autoimmune disease history within 2 years (subjects with vitiligo, psoriasis, alopecia, or Graves' disease not requiring systemic treatment, hypothyroidism only requiring thyroid replacement, or type I diabetes only requiring insulin can be enrolled).
- Has a known history of primary immunodeficiency diseases.
- Has a known active pulmonary tuberculosis.
- Has a known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
- Is human immunodeficiency virus (HIV)-infected (has positive anti-HIV antibody).
- Has an active or poorly controlled serious infections.
- Has symptomatic congestive heart failure (NYHA Class II-IV) or symptomatic or poorly controlled arrhythmia.
- Has uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg) despite standard treatment.
- Had any arterial thromboembolic event within 6 months prior to enrollment, including myocardial infarction, unstable angina, cerebrovascular accident, or transient cerebral ischemic attack.
- Has significant malnutrition, such as those requiring continuous parenteral nutrition ≥7 days. Allowed are those who received intravenous treatment for malnutrition that ended more than 4 weeks before the first dose of study treatment.
- Has a history of clinically significant deep venous thrombosis, pulmonary embolism, or other serious thromboembolic events within 3 months prior to enrollment (having an implantable port or catheter-related thrombosis or incidental pulmonary embolism detected on scan without symptoms or superficial venous thrombosis is not considered to be a "serious" thromboembolisms).
- Has uncontrolled metabolic disorders, non-malignant organ or systemic diseases, or cancer-related secondary diseases that may lead to higher medical risks and/or survival evaluation uncertainties.
- Has severe pulmonary dysfunction.
- Has hepatic encephalopathy, hepatorenal syndrome, or cirrhosis with Child-Pugh Class B or C.
- Has bowel obstruction or history of any of the following diseases: inflammatory bowel disease, extensive bowel resection (partial colectomy or extensive small intestine resection accompanied with chronic diarrhea), Crohn's disease, or ulcerative colitis.
- Has known acute or chronic active hepatitis B (positive HBsAg and hepatitis B (HBV) DNA viral load ≥ 103 copies/mL or > 200 IU/mL), or acute or chronic active hepatitis C (positive hepatitis C [HCV] antibody and detectable HCV RNA).
- Has history of gastrointestinal (GI) perforation and/or fistula within 6 months prior to study enrollment (having a gastrostomy or enterostomy is allowed).
- Has interstitial lung disease requiring corticosteroids.
- Has history of other primary malignant tumors, excluding:
- Malignant tumors that achieved a complete response (CR) at least 2 years prior to enrollment and expected to require no treatment during the trial.
- Adequately treated nonmelanoma skin cancer or lentigo maligna with no sign of disease recurrence.
- Adequately treated carcinoma in situ with no sign of disease recurrence.
- Prostate cancer, CLL or other cancers where the indolent nature of tumor allows for and patient is under active surveillance.
- Is pregnant or breastfeeding.
- Has an acute or chronic diseases, psychiatric disorders, or laboratory abnormality that may lead to the following consequences: increased investigational drug-related risks, or interference with interpretation of trial results, or is otherwise considered ineligible for participating in the trial by the investigators.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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)
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).
Read more
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.
Read the 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.
- Conditions
- Cancer of Unknown Primary Site
- Being tested
- Sintilimab
- Medical subject headings
- Neoplasms, Unknown Primary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SintilimabDrug
Given by IV
| Study group | Role | What they receive |
|---|---|---|
| Treatment (sintilimab) | Experimental | The study drug is sintilimab. The first dose of study treatment should start on Day 1 of Cycle 1. For the rest of the treatment cycles, the study treatment can be administered 3 day before or 3 days after the scheduled day of administration. Treatment can be delayed for up to 1 week if the administration day is on a holiday or if the subject is otherwise unavailable. Receives: Drug: Sintilimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Confirmed Objective Response Rate (cORR) by RECISTv1.1
Measured: 1 year
Secondary outcomes (2)
Progression-free Survival (PFS)
Measured: 1 year
Overall Survival (OS)
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Aug 2021
- Study start26 Aug 2021
- Primary completion3 Apr 2025
- Study completion3 Apr 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Cancer of Unknown Primary SiteStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Innovent Biologics (Suzhou) Co. Ltd.
- Responsible party
- Sponsor
- Investigators
- Kanwal Raghav, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05024968
- Sponsor's protocol ID
- 2020-0902
- Other IDs
- NCI-2021-08870
- Status last verified
- Feb 2026
- First submitted
- 19 Aug 2021
- Last updated
- 25 Feb 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT05024968
- Acronym / sponsor ID
- 2020-0902
- Conditions
- Cancer of Unknown Primary Site
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Innovent Biologics (Suzhou) Co. Ltd.
- Study start
- 26 Aug 2021 (actual)
- Primary completion
- 3 Apr 2025 (actual)
- Study completion
- 3 Apr 2025 (actual)
- First posted
- 27 Aug 2021 (actual)
- Results
- Posted 25 Feb 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (sintilimab) | Experimental | Drug: SintilimabThe study drug is sintilimab. The first dose of study treatment should start on Day 1 of Cycle 1. For the rest of the treatment cycles, the study treatment can be administered 3 day before or 3 days after the scheduled day of administration. Treatment can be delayed for up to 1 week if the administration day is on a holiday or if the subject is otherwise unavailable. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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.
- Is refractory or intolerant to at least one line of systemic chemotherapy. Patient ineligible for cytotoxic chemotherapy due to contraindications will be eligible.
- Has an ECOG PS of 0 - 2.
- 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.
- Is able to provide archival or fresh tissues for correlative analysis with obtainable results.
Key exclusion criteria (36 listed)
- 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.
- 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.
- Has received palliative therapy for a local lesion within 2 weeks prior to the first dose.
- 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.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SintilimabGiven by IV | Drug | Treatment (sintilimab) |
Primary outcome
Confirmed Objective Response Rate (cORR) by RECISTv1.1
Time frame: 1 year
2 secondary outcomes
Progression-free Survival (PFS)
Time frame: 1 year
Overall Survival (OS)
Time frame: 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Feb 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- M D Anderson Cancer CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kanwal Raghav principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sintilimab in people with Cancer of Unknown Primary Site, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 36 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Feb 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Confirmed Objective Response Rate (cORR) by RECISTv1.1 (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Feb 2026; AzTrials last refreshed its copy on 26 Oct 2026.