Two-cohort Study of Toripalimab(PD1)+Lenvatnib, or Gemox+Lenvatinib in Advanced Intrahepatic Cholangiocarcinoma

Cholangiocarcinoma, Intrahepatic Clinical Trial

Official title:

A Randomized, Open, Two-cohort Phase 2 Study of Toripalimab(PD1) Combined With Lenvatnib, or Gemox Chemotherapy Combined With Lenvatinib as First-line Therapy in Patients With Advanced or Unresectable Intrahepatic Cholangiocarcinoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04361331
• Other study ID #: zs-ICC-2020
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: March 6, 2020
• Est. completion date: December 6, 2021

Study information

• Verified date: July 2021
• Source: Shanghai Zhongshan Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

We aim to explore the effects and safety of the two cohorts of toripalimab combined with lenvatinib or gemox combined with lenvatinib as first-line therapy in advanced or unresectable intrahepatic cholangiocarcinoma

Description:

For advanced intrahepatic cholangiocarcinoma (ICC) that cannot be surgically removed or accompanied by metastasis, the NCCN guidelines (NCCN guidelines hepatobiliary cancer, 2019) recommend that the current treatment options are limited, mainly recommending gemcitabine combined with platinum-based antitumor drugs (cisplatin, oxaliplatin, etc.) chemotherapy as first-line treatment. Adding targeted drugs can enhance the anti-tumor effect. For those with microsatellite instability, it is recommended to add anti-PD1(programmed cell death protein 1) antibody. Gemox chemotherapy (oxaliplatin + gemcitabine) has been used in the treatment of advanced intrahepatic cholangiocarcinoma, but the efficacy is still not satisfactory. Lenvatinib is a small-molecule multi-kinase inhibitor that is currently approved for first-line treatment of advanced hepatocellular carcinoma. In recent years, the anti-PD1 antibody has shown efficacy in the treatment of primary liver cancer. Lenvatinib combined with anti-PD1 antibody or chemotherapy may have a better effect than single use for advanced ICC. At present, lenvatinib combined with anti-PD1 antibody or lenvatinib combined with Gemox in the first-line treatment of advanced ICC has not been reported.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 60
• Est. completion date: December 6, 2021
• Est. primary completion date: September 6, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• 1. The patient must be required to sign an informed consent; 2. Age 18-75 years old, male or female; 3. ECOG performance status score (PS score) 0 or 1 point; 4. Child-Pugh score A; 5. Intrahepatic cholangiocarcinoma confirmed by histopathology; agree to provide previously stored tumor tissue samples or fresh biopsy tumor lesions;

6. Unresectable ICC patients or postoperative ICC recurrence and metastasis, without systematic treatment within 6 months; 7. The functional indicators of vital organs meet the following requirements

1. Neutrophils =1.5 * 109 / L; platelets =100 * 109 / L; hemoglobin =9g / dl; serum albumin =3g/dl;

2. Thyroid stimulating hormone (TSH) = 1 times the upper limit of normal value(ULN), T3 and T4 are in the normal range;

3. Bilirubin = 1.5 times ULN; ALT and AST = 3 times ULN;

4. Serum creatinine = 1.5 times ULN, creatinine clearance rate = 60ml/min (calculated using Cockcroft-Gault formula); 8. Subject has at least 1 measurable lesion (according to RECIST1.1); 9. Non-lactating or pregnant women, contraception during or 3 months after treatment.

Exclusion Criteria:

• 1. Pathological diagnosis of hepatocellular carcinoma, mixed hepatocellular carcinoma and other non-cholangiocarcinoma malignancies; 2. Existing or concurrently suffering from other malignant tumors, except for fully treated non-melanoma skin cancer, cervical carcinoma in situ, and papillary thyroid cancer; 3. Have used lenvatinib or gemcitabine-based chemotherapy within 6 months or have used PD1 monoclonal antibody and PD-L1 monoclonal antibody treatment; 4. Severe cardiopulmonary and renal dysfunction; 5. Hypertension that is difficult to control by the drug (systolic blood pressure (BP) =140 mmHg and / or diastolic blood pressure =90 mmHg) (based on the average of =3 BP readings obtained from =2 measurements); 6. Abnormal blood coagulation function (PT> 14s), have bleeding tendency or are receiving thrombolysis or anticoagulation treatment; 7. HBV DNA> 2000 copies/ml and HCV RNA>1000 after antiviral treatment; 8. Have a history of esophagogastric varices, with significant clinically significant bleeding symptoms or a clear tendency to appear within 3 months before enrollment; 9. Active infection requiring systemic treatment and treatment; patients with active tuberculosis infection within 1 year before enrollment; a history of active tuberculosis infection more than 1 year before enrollment, have not received regular anti-TB treatment or tuberculosis Still in the active period; 10. Human immunodeficiency virus (HIV, HIV1/2 antibody) positive; 11. Have a history of psychotropic substance abuse, alcohol or drug abuse; 12. Known to have a history of severe allergies to any monoclonal antibodies, anti-angiogenic targeted drugs, and platinum or gemcitabine; 13. Other factors that may affect the safety of subjects or test compliance as judged by the investigator. Such as serious illness (including mental illness) requiring combined treatment, severe laboratory abnormalities, or other family or social factors.

Related Conditions & MeSH terms

• Cholangiocarcinoma
• Cholangiocarcinoma, Intrahepatic

Intervention

Drug:
• Lenvatinib combined with gemox
Arm2: Lenvatinib + gemox
• Toripalimab combined with lenvatinib
Toripalimab combined with lenvatinib

Locations

Country	Name	City	State
China	Huang xiaoyong	Shanghai
China	Zhongshan hospital	Shanghai	??

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Zhongshan Hospital

Country where clinical trial is conducted

China, 

References & Publications (4)

André T, Tournigand C, Rosmorduc O, Provent S, Maindrault-Goebel F, Avenin D, Selle F, Paye F, Hannoun L, Houry S, Gayet B, Lotz JP, de Gramont A, Louvet C; GERCOR Group. Gemcitabine combined with oxaliplatin (GEMOX) in advanced biliary tract adenocarcino — View Citation

El-Khoueiry AB, Sangro B, Yau T, Crocenzi TS, Kudo M, Hsu C, Kim TY, Choo SP, Trojan J, Welling TH Rd, Meyer T, Kang YK, Yeo W, Chopra A, Anderson J, Dela Cruz C, Lang L, Neely J, Tang H, Dastani HB, Melero I. Nivolumab in patients with advanced hepatocel — View Citation

Kudo M, Finn RS, Qin S, Han KH, Ikeda K, Piscaglia F, Baron A, Park JW, Han G, Jassem J, Blanc JF, Vogel A, Komov D, Evans TRJ, Lopez C, Dutcus C, Guo M, Saito K, Kraljevic S, Tamai T, Ren M, Cheng AL. Lenvatinib versus sorafenib in first-line treatment o — View Citation

Zhu AX, Finn RS, Edeline J, Cattan S, Ogasawara S, Palmer D, Verslype C, Zagonel V, Fartoux L, Vogel A, Sarker D, Verset G, Chan SL, Knox J, Daniele B, Webber AL, Ebbinghaus SW, Ma J, Siegel AB, Cheng AL, Kudo M; KEYNOTE-224 investigators. Pembrolizumab i — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective response rate	Objective response rate of advanced and unresectable intrahepatic cholangiocarcinoma	12 months
Secondary	Safety: the potential side effects	The potential side effects	12 months
Secondary	Overall survival	From the beginning date of combined therapy to the date of death	12 months
Secondary	Progression free survival	From the beginning date of combined therapy to disease progression or death, whichever occurs first.	12 months