Brief Title
Apatinib Plus Camrelizumab in Patients With Previously Treated Advanced Biliary Tract Cancer
Official Title
Apatinib Plus Camrelizumab in Patients With Previously Treated Advanced Biliary Tract Cancer (ACABC): A Prospective Clinical Study
Brief Summary
The investigators design a prospective clinical study to explore the efficacy and safety of
apatinib plus camrelizumab in pretreated patients with advanced biliary tract malignant
tumors and to analyze potential biomarkers of therapeutic response.
Detailed Description
This was a non-randomized, single institutional, open-label, prospective trial designed to
evaluate the efficacy and safety of apatinib in combination with camrelizumab for patients
with biliary tract malignant tumors.
It is estimated that 20 patients who met the study criteria will be enrolled in PUMCH and
treated with aptinib and camrelizumab. The investigators will follow up and collect subjects'
data each month to evaluate the efficacy and safety of treatment, including treatment related
adverse events, overall survival and time to progression and objective response. Multi-omics
data analysis will be used to find potential biomarkers of treatment response.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Progression-free Survival (PFS)
Secondary Outcome
Overall Survival (OS)
Condition
Biliary Tract Cancer
Intervention
Apatinib plus Camrelizumab
Study Arms / Comparison Groups
Apatinib plus Camrelizumab
Description: Apatinib is a multi-target TKI, which selectively inhibits VEGFR-2. Camrelizumabb is a anti-human PD-1 monoclonal antibody.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
22
Start Date
December 1, 2018
Completion Date
January 1, 2021
Primary Completion Date
December 1, 2020
Eligibility Criteria
Inclusion Criteria:
1. Patients must have histologically or cytologically confirmed cholangiocarcinoma
including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma and
gallbladder cancer. Patients with ampullary carcinoma are not eligible.
2. Patients must have failed or are intolerant to one line of systemic chemotherapy
treatment.
3. Patients who received adjuvant chemotherapy and had evidence of disease recurrence
within 6 months of completion of the adjuvant treatment are also eligible. If the
patient received adjuvant treatment and had disease recurrence after 6 months,
patients will only be eligible after failing or having intolerance to one line of
systemic chemotherapy used to treat the disease recurrence.
4. Age ≥ 18 years.
5. Eastern Cooperative Oncology Group (ECOG) Performance Status Assessment of 0-2.
6. Life expectancy of at least 12 weeks (3 months).
7. Subjects must be able to understand and be willing to sign the written informed
consent form. A signed informed consent form must be appropriately obtained prior to
the conduct of any trial-specific procedure. Subjects must be willing and able to
comply with scheduled visits, treatment schedule, laboratory testing, and other study
requirements.
8. All acute toxic effects of any prior treatment have resolved to NCI-CTCAE v4.0 Grade 1
or less at the time of signing the Informed Consent Form (ICF) except for alopecia.
9. For patients with advanced biliary tract cancer, liver function status Child-Pugh
Class A or B (score<=7).
10. Adequate bone marrow, liver and liver function as assessed by the following laboratory
requirements: Total bilirubin ≤ 1.5 x the upper limits of normal (ULN), except for
subjects with Gilbert Syndrome who can have bilirubin <3. Alanine aminotransferase
(ALT) and aspartate amino-transferase (AST) ≤ 2.5 x ULN (≤ 5 x ULN for subjects with
liver involvement of their cancer or stent placement). Alkaline phosphastase limit ≤
2.5 x ULN (≤ 5 x ULN for subjects with liver involvement of their cancer). Serum
creatinine <2 x ULN. Hematologic parameters as follows: Platelet count ≥ 100,000 /mm3.
Hemoglobin (Hb) ≥ 9 g/Dl. Absolute neutrophil count (ANC) ≥1000/mm. Blood transfusion
to meet the inclusion criteria will be allowed.
11. Women of childbearing potential must have a negative serum or urine pregnancy test
(minimum sensitivity of 25 IU/L or equivalent units of HCG) performed within24 hours
prior to the start of nivolumab Post-menopausal women (defined as no menses for at
least 1 year) and surgically sterilized women are not required to undergo a pregnancy
test.
12. Subjects (men and women) of childbearing potential must agree to use adequate
contraception beginning at the signing of the ICF until at least 3 months after the
last dose of study drug. The definition of adequate contraception will be based on the
judgment of the principal investigator or a designated associate.
13. Patients with history of hepatitis B and hepatitis C will be eligible but patients
with hepatitis B must be started on antiviral therapy prior to beginning study therapy
14. Availability of archival tumor tissue for biomarkers analysis (FFPE block or cell
block will be required). Specimen from primary site will be allowed. Patients must
have at least 10 slides available. Repeat biopsy to obtain sufficient tissue for 10
slides is allowed.
Exclusion Criteria
1. Subjects with active CNS metastases are excluded. If CNS metastases are treated and
subjects are at neurologic baseline for at least 2 weeks prior to enrollment, they
will be eligible but will need a Brain MRI prior to enrollment. Subjects must be off
corticosteroids or on a stable or decreasing dose of ≤ 10 mg daily prednisone (or
equivalent).
2. Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo,
type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only
requiring hormone replacement, or conditions not expected to recur in the absence of
an external trigger are permitted to enroll
3. Subjects with a condition requiring systemic treatment with either corticosteroids
(>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14
days of enrollment. Inhaled or topical steroids, and adrenal replacement steroid doses
> 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune
disease.
4. Previous or concurrent cancer within 3 years prior to treatment start EXCEPT for
curatively treated cervical cancer in situ, non-melanoma skin cancer, superficial
bladder tumors [Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor invades
lamina propria)].
5. Known history of human immunodeficiency virus (HIV) infection or acquired
immunodeficiency syndrome (AIDS).
6. Child Pugh C disease
7. History of severe hypersensitivity reactions to other monoclonal antibodies
8. History of allergy or intolerance to study drug components or
Polysorbate-80-containing infusions
9. Substance abuse, medical, psychological or social conditions that may interfere with
the patient's participation in the study or evaluation of the study results.
10. History or concurrent condition of interstitial lung disease of any grade or severely
impaired pulmonary function.
11. Unresolved toxicity higher than CTCAE grade 1 attributed to any prior
therapy/procedure excluding alopecia.
12. Pregnant or breast-feeding patients. Women of childbearing potential must have a
negative serum or urine pregnancy test (minimum sensitivity of 25 IU/L or equivalent
units of HCG) performed within 24 hours prior to the start of nivolumab and a negative
result must be documented before start of treatment.
13. Any illness or medical conditions that are unstable or could jeopardize the safety of
the patient and his/her compliance in the study.
14. Anticancer chemotherapy during the study or within 4 weeks of study enrollment.
Subjects must have recovered from the toxic effects of the previous anti-cancer
chemotherapy (with the exception of alopecia). Anti-cancer therapy is defined as any
agent or combination of agents with clinically proven anti-tumor activity administered
by any route with the purpose of affecting the malignancy, either directly or
indirectly, including palliative and therapeutic endpoints.
15. Hormonal therapy during the study or within 2 weeks of first study enrollment.
16. Investigational drug therapy outside of this trial during or within 4 weeks of first
study treatment.
17. Notably, patients with severe esophageal varices or presented with positive fecal
occult blood were also excluded.
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Hai-Tao Zhao, M.D., ,
Location Countries
China
Location Countries
China
Administrative Informations
NCT ID
NCT04642664
Organization ID
JS-2160
Responsible Party
Sponsor
Study Sponsor
Peking Union Medical College Hospital
Study Sponsor
Hai-Tao Zhao, M.D., Principal Investigator, Peking Union Medical College Hospital
Verification Date
November 2020