Sintilimab in Cancer of Unknown Primary

  • STATUS
    Recruiting
  • days left to enroll
    90
  • participants needed
    45
  • sponsor
    M.D. Anderson Cancer Center
Updated on 4 October 2022

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.

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.

Details
Condition Neoplasms, Unknown Primary
Treatment Sintilimab
Clinical Study IdentifierNCT05024968
SponsorM.D. Anderson Cancer Center
Last Modified on4 October 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

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
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)/(72serum creatinine(mg/dL))
Male: CrCl=((140-age)weight(kg)1.00)/(72serum creatinine(mg/dL)) 8. 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. 9. Is expected to survive 12 weeks. 10. 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). 11. 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

Exclusion Criteria

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
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. 30. Is pregnant or breastfeeding. 31. 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
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