Trial Title:
Study to Evaluate the Efficacy and Safety of Immunotherapy With Axitinib in Advanced Collecting Duct Carcinoma
NCT ID:
NCT06211114
Condition:
Collecting Duct Carcinoma
Conditions: Official terms:
Carcinoma
Carcinoma, Ductal
Carcinoma, Renal Cell
Axitinib
Conditions: Keywords:
Immune Checkpoint Inhibitors
Axitinib
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
PD-(L)1 inhibitor
Description:
Toripalimab 240mg or Tirelizumab 200mg or pembrolizumab 200mg intravenously every 3 weeks
Arm group label:
PD-(L)1 inhibitor + Axitinib
Intervention type:
Drug
Intervention name:
Axitinib
Description:
axitinib 5mg orally twice daily
Arm group label:
PD-(L)1 inhibitor + Axitinib
Summary:
This is a phase II trial to evaluate the efficacy and safety of immune checkpoint
inhibitors in combination with axitinib for previously treated advanced collecting duct
carcinoma.
Detailed description:
Patients meeting specific inclusion and exclusion criteria will be enrolled in two
stages, 8 patients in stage 1 and 22 patients in stage 2. Stage 2 will enroll if 1 or
more patients exhibit a response at week 9 or later in stage 1 in the study. All enrolled
patients will be treated with immune checkpoint inhibitors in combination with axitinib
until disease progression. Efficacy will be assessed by tumor measurements using CT and
MRI (when indicated) scans and physical exam at baseline, and scans and physical exam of
all disease-involved areas every 9 weeks until progression. Safety will be assessed by
periodic physical exams, clinical laboratory studies, and adverse events. All patients
will have a follow-up visit 90 days following last study drug treatment.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Fully understand and be willing to provide written informed consent.
2. Male or female with age ≥ 18 years and <80 years.
3. Have received prior systemic therapy after previous metastasis for collecting duct
carcinoma, histologically confirmed diagnosis of unresectable, recurrent or
metastatic collecting duct carcinoma.
4. Having at least one measurable disease per RECIST 1.1. Lesions situated in a
previously irradiated area are considered measurable if re-progression has been
demonstrated.
5. ECOG PS 0 or 1.
6. Adequate function of vital organs:
6.1 Bone marrow function (without blood or blood products transfusion, without
hematopoietic stimulating factor or other medication to improve blood cell count
within 2 days prior to first dose of study drug): Absolute neutrophil count (ANC) ≥
1.5×109/L. Platelets ≥ 100×109/L. Hemoglobin ≥ 9.0g/dL or ≥ 5.6mmol/L. 6.2 Renal
function: Serum creatinine ≤ 1.5×ULN 6.3 Hepatic function:Serum total bilirubin
≤1.5×ULN or total bilirubin levels >1.5×ULN with direct bilirubin ≤ ULN. AST and ALT
≤2.5 × ULN, ≤5×ULN in those with hepatic metastasis.
6.4 Endocrine function: Normal thyroid stimulating hormone, or abnormal TSH whilst
normal FT3 and FT4.
6.5 Coagulation function: International normalized ratio (INR) or prothrombin time
(PT) ≤1.5×ULN, and activated partial thromboplastin time (aPTT) ≤1.5×ULN, Subjects
receiving anticoagulant therapy (e.g., heparin or warfarin) may participate in the
study with PT or APTT levels within the scope of the proposed therapy and monitored
during study treatment.
6.6 Left ventricular ejection fraction (LVEF) ≥ 50%.
7. Being willing and able to comply with scheduled visits, treatment plan, laboratory
tests and other study procedures.
8. Female subjects of childbearing potential must have a negative serum pregnancy test
within 7 days prior to the first treatment dose. Female subjects of childbearing
potential and male subjects whose partners are of childbearing potential must agree
to use a highly effective methods of contraceptive throughout the study and for 180
days after the last dose of study therapy.
Exclusion Criteria: Exclusion criteria: Patients with any of the following conditions
will not be included in the study:
1. Prior Anti-PD-1, PD-L1 or axitinib.
2. Has participated or is currently participating in a trial of investigational agent
within 4 weeks prior to the first dose of study treatment, unless observational
(non-interventional) clinical study or follow-up period of interventional study.
3. Had major surgery (judged by investigators) within 4 weeks prior to the first dose
of study treatment or has not recovered from prior surgery.
4. Has traditional Chinese medicine or Chinese patent medicine preparation with
anti-cancer indication within 2 weeks prior to the first dose of study treatment.
5. Requiring corticosteroids (Prednisone >10 mg/day or equivalent analogue) or other
immunosuppressive agents within 2 weeks prior to the first dose of study treatment.
6. Patients without active autoimmune disease using inhaled prednisone >10 mg/day
will not be excluded from the study.
7. Has a history of organ transplantation or required long-term treatment with
corticosteroids.
8. Hypothyroidism, hypoadrenalism or hypopituitarism that can be controlled only with
hormone replacement therapy, type I diabetes, psoriasis or leucoderma not requiring
systematic treatment.
9. Not recovered from the toxicity of prior anti-cancer therapy, i.e., not recovered to
baseline, Grade 0-1 (NCI-CTCAE 5.0, except alopecia) or per inclusion/exclusion
criteria in protocol. Under rational expectation, irreversible toxicities (e.g.,
hearing loss) which will not be worsened by study treatments may be enrolled in the
study.
10. Has an additional malignancy that has progressed or required treatment within 5
years prior to randomization (basal cell carcinoma of the skin, squamous cell
carcinoma of the skin, superficial bladder cancer, or carcinoma in situ such as
breast cancer, prostate cancer are acceptable if they have undergone potentially
curative therapy；Remarks: Localized low-risk prostate cancer [ patietns with stage ≤
T2a, Gleason score ≤ 6 and PSA < 10ng/mL at the time of diagnosis (as measured) can
be included in this study if the subject has received radical therapy and has no
evidence for biochemical recurrence(PROSTATE specific antigen,PSA)].
11. Has a history of active central nervous system (CNS) metastasis or CNS metastasis
had been confirmed by radiological examination (MRI or CT) at baseline within 30
days prior to the first dose of study drug. Subjects may participate who had been
stable at least for 3 months after prior surgery or RT for brain or meningeal
metastasis and discontinued systemic treatment with corticosteroids (Prednisone >10
mg/day or equivalent analogue) for at least 4weeks. Subjects may participate in the
study if their CNS metastases are adequately treated to meet the requirements
specified in the inclusion criteria, and their neurological symptoms recover to
grade 0-1 (CTCAE 5.0) for at least 2 weeks prior to inclusion (except for residual
signs or symptoms associated with CNS treatment).
12. Poorly controlled hypertension (systolic blood pressure ≥ 150mmHg and/or diastolic
blood pressure ≥ 90mmHg).
13. Presence of the following cardiovascular events within 6 months prior to
randomization: Myocardial infarction Unstable angina pectoris Cardiac angioplasty or
stent Coronary/peripheral artery bypass graft Grade III or IV congestive heart
failure per New York Heart Association Cerebrovascular accident or transient
ischemic attack QT interval (QTc) ≥ 480 msec corrected with heart rate (Bazett's
formula); 14. Has active hemorrhage or history of other significant hemorrhage
episodes within 30 days prior to randomization.
15. Has deep vein thrombosis or pulmonary embolism within 6 months prior to
randomization.
16. Has arterial thrombosis within 12 months prior to randomization. 17. Has clinically
significant gastrointestinal (GI) abnormalities including: Malabsorption, total
gastrectomy or any other condition that might affect the absorption of orally taken
medication.
Active ulcer under treatment in the past 6 months; Active GI bleeding (e.g., hematemesis,
hematochezia or melena) in the past 3 months, and without evidence of resolution
documented by endoscopy or colonoscopy.
Intraluminal metastatic lesion with suspected hemorrhage, inflammatory bowel disease,
ulcerative colitis, GI perforation, or other GI conditions associated with increased risk
of perforation.
18. Has a history of or current (non-infective) pneumonia/ interstitial lung disease
that required steroids.
19. Has an active infection requiring systemic therapy. Has a known history of Human
Immunodeficiency Virus (HIV) infection (HIV antibody positive), HBV or HCV infection
(Patients with positive HBsAg or negative HBsAg, but positive HBcAb will be enrolled
in the study when HBV DNA was tested in central laboratory and lower than ULN.
Patients with a history of HCV infection may participate in the study if the result
of HCV RNA test was negative during screening period).
20. Has received a live virus vaccine within 30 days prior to randomization, including
(but not limited to) mumps, rubella, measles, varicella/ herpes zoster (chicken
pox), yellow fever, rabies, Bacille Calmette-Guérin (BCG) and typhoid vaccine.
Inactivated virus vaccines are allowed.
21. Has a history of hypersensitivity reaction, including (but not limited to)
antibodies and TKIs.
22. Known history of psychiatric disorders or drug abuse. 23. Has evidence of inadequate
wound healing. 24. Has current use (within 7 days of randomization) or anticipated
need for treatment drugs what are known strong CYP3A4/5 inhibitor and CYP3A4/5
inducer (including, but not limited to, carbamazepine, phenobarbital, phenytoin,
rifabutin, rifampin and St. John's wort) or the drugs that are known with
proarrhythmic potential (including, but not limited to, terfenadine, quinidine,
procainamide, disopyramide, sotalol, probucol and benazapril, etc.).
25. Has a history or current evidence on any condition, therapy or laboratory
abnormality that might confound the results of the study, interfere with subject's
participation for the full duration of the study, or is not in the best interest of
subject to participate, in the opinion of investigators.
Gender:
All
Minimum age:
18 Years
Maximum age:
80 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Beijing Cancer Hospitao
Address:
City:
Beijing
Zip:
100086
Country:
China
Contact:
Last name:
Xinan Sheng, MD.
Phone:
+86-10-88196348
Email:
doctor_sheng@126.com
Investigator:
Last name:
Xieqiao Yan, MD.
Email:
Sub-Investigator
Investigator:
Last name:
Li Zhou, MD.
Email:
Sub-Investigator
Start date:
February 2024
Completion date:
February 2027
Lead sponsor:
Agency:
Peking University Cancer Hospital & Institute
Agency class:
Other
Source:
Peking University Cancer Hospital & Institute
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06211114
