A Clinical Study of a Preoperative Translational Therapy for Unresectable Gallbladder Cancer

Unresectable Gallbladder Cancer Clinical Trial

Official title:

A Single-arm, Multicenter, Phase II Clinical Study of the Efficacy and Safety of Carrilizumab Combinated With Gemcitabine and Oxaliplatin (GEMOX) as a Preoperative Translational Therapy for Unresectable Gallbladder Cancer

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05919095
• Other study ID #: SYSKY-2022-516-02
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: June 30, 2023
• Est. completion date: June 30, 2026

Study information

• Verified date: June 2023
• Source: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
• Contact: Rui Zhang, PhD
• Phone: 020-34078840
• Email: zhangr95[@]mail.sysu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is an open-label,multicenter ,non-randomized,single arm exploratory study. The objective of this study is to evaluate the efficacy and safety of PD-1 antibody plus GEMOX as preoperative translational therapy for unresectable gallbladder cancer.

Description:

The aim of this study was to evaluate the efficacy and safety of carrilizumab in combination with gemcitabine and oxaliplatin (GEMOX) as a preoperative conversion therapy for unresectable gallbladder cancer. Patients with unresectable gallbladder cancer were enrolled to receive gemcitabine 1000 mg/m2 D1, D8 + oxaliplatin 100 mg/m2, D1 + carrilizumab 200 mg, D1, in 21-day cycles for 6-8 cycles, with changes in serum tumor parameters assessed at each course and abdominal CTA performed every two courses.The above treatment was terminated if the CT evaluation revealed disease progression, and the investigator could adjust the treatment regimen according to the guideline. The primary outcome measure of this study is the tumor radical resection rate; secondary outcome measure are objective response rate, disease control rate, progression-free survival, and overall survival. The safety indicators are the incidence and severity of adverse events (AE) and serious adverse events (SAE) according to NCI-CTCAEv5.0 criteria. Thirty-seven cases are expected to be enrolled in this study.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 37
• Est. completion date: June 30, 2026
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. The patient must sign an informed consent form;

2. Age 18-75 years old, both male and female;

3. ECOG performance status score (PS score) 0 or 1 point;

4. Child-Pugh score A period;

5. Patients with advanced or recurrent metastatic gallbladder cancer who are not suitable for radical surgery (R0), or non-radical surgery (R1), or palliative surgery, as confirmed by pathological histology or cytology.

6. Have not received any systemic treatment within 6 months;

7. The functional indicators of important 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) = 2 times the upper limit of normal, and T3 and T4 are in the normal range; (3)Bilirubin = 1.5 times the upper limit of normal; ALT and AST = 3 times the upper limit of normal; (4)Serum creatinine = 1.5 times the upper limit of normal, and creatinine clearance = 60ml/min (calculated by Cockcroft-Gault formula);

8. The subject has at least 1 measurable lesion (according to RECIST1.1);

9. For women who are not breastfeeding or pregnant, use contraception during treatment or 12 months after the end of treatment.

Exclusion Criteria:

1. Past or simultaneous suffering from other malignant tumors, except for fully treated non-melanoma skin cancer, cervical carcinoma in situ, and thyroid papillary carcinoma;

2. Have used gemcitabine-based chemotherapy or have used PD-1 monoclonal antibody or PD-L1 monoclonal antibody treatment within 6 months;

3. Severe cardiopulmonary and renal dysfunction;

4. Hypertension that is difficult to control with drugs (systolic blood pressure (BP) =140 mmHg and/or diastolic blood pressure =90mmHg) (based on the average of =3 BP readings obtained by =2 measurements);

5. Abnormal coagulation function (PT>14s), have bleeding tendency or are receiving thrombolysis or anticoagulation therapy;

6. After antiviral treatment, HBV DNA>2000 copies/ml, HCV RNA>1000;

7. A history of esophageal and gastric varices, significant clinically significant bleeding symptoms or a clear tendency to appear within 3 months before enrollment;

8. Active infections requiring systemic treatment; patients with active tuberculosis infection within 1 year before enrollment; a history of active tuberculosis infection more than 1 year before enrollment, and no formal anti-tuberculosis treatment or tuberculosis Still in the active period;

9. Human immunodeficiency virus (HIV, HIV1/2 antibody) positive;

10. A history of psychotropic drug abuse, alcohol or drug abuse;

11. Known to have a history of severe allergies to any monoclonal antibodies, platinum drugs, or gemcitabine;

12. Other factors judged by the investigator may affect the safety of the subjects or the compliance of the trial. Such as serious diseases (including mental illness) that require combined treatment, serious laboratory abnormalities, or other family or social factors.

Related Conditions & MeSH terms

• Gallbladder Neoplasms
• Unresectable Gallbladder Cancer

Intervention

Drug:
• Carrilizumab plus GEMOX
PD-1 antibody,200mg,D1,intravenous infusion, the administration time is 60 (+15) minutes. GEMOX chemotherapy : gemcitabine 1000mg/m2,D1,D8;oxaliplatin 100mg/m2,D1intravenous infusion.Three weeks is a course of treatment.

Locations

Country	Name	City	State
China	Sun Yat-sen Memorial Hospital, Sun Yat-sen University	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Country where clinical trial is conducted

China, 

References & Publications (10)

Baiu I, Visser B. Gallbladder Cancer. JAMA. 2018 Sep 25;320(12):1294. doi: 10.1001/jama.2018.11815. No abstract available. — View Citation

Chaudhari VA, Ostwal V, Patkar S, Sahu A, Toshniwal A, Ramaswamy A, Shetty NS, Shrikhande SV, Goel M. Outcome of neoadjuvant chemotherapy in "locally advanced/borderline resectable" gallbladder cancer: the need to define indications. HPB (Oxford). 2018 Sep;20(9):841-847. doi: 10.1016/j.hpb.2018.03.008. Epub 2018 Apr 26. — View Citation

Chen X, Wu X, Wu H, Gu Y, Shao Y, Shao Q, Zhu F, Li X, Qian X, Hu J, Zhao F, Mao W, Sun J, Wang J, Han G, Li C, Xia Y, Seesaha PK, Zhu D, Li H, Zhang J, Wang G, Wang X, Li X, Shu Y. Camrelizumab plus gemcitabine and oxaliplatin (GEMOX) in patients with advanced biliary tract cancer: a single-arm, open-label, phase II trial. J Immunother Cancer. 2020 Nov;8(2):e001240. doi: 10.1136/jitc-2020-001240. — View Citation

Creasy JM, Goldman DA, Dudeja V, Lowery MA, Cercek A, Balachandran VP, Allen PJ, DeMatteo RP, Kingham TP, D'Angelica MI, Jarnagin WR. Systemic Chemotherapy Combined with Resection for Locally Advanced Gallbladder Carcinoma: Surgical and Survival Outcomes. J Am Coll Surg. 2017 May;224(5):906-916. doi: 10.1016/j.jamcollsurg.2016.12.058. Epub 2017 Feb 13. — View Citation

Kato A, Shimizu H, Ohtsuka M, Yoshitomi H, Furukawa K, Takayashiki T, Nakadai E, Kishimoto T, Nakatani Y, Yoshidome H, Miyazaki M. Downsizing Chemotherapy for Initially Unresectable Locally Advanced Biliary Tract Cancer Patients Treated with Gemcitabine Plus Cisplatin Combination Therapy Followed by Radical Surgery. Ann Surg Oncol. 2015 Dec;22 Suppl 3:S1093-9. doi: 10.1245/s10434-015-4768-9. Epub 2015 Aug 4. — View Citation

Lamarca A, Palmer DH, Wasan HS, Ross PJ, Ma YT, Arora A, Falk S, Gillmore R, Wadsley J, Patel K, Anthoney A, Maraveyas A, Iveson T, Waters JS, Hobbs C, Barber S, Ryder WD, Ramage J, Davies LM, Bridgewater JA, Valle JW; Advanced Biliary Cancer Working Group. Second-line FOLFOX chemotherapy versus active symptom control for advanced biliary tract cancer (ABC-06): a phase 3, open-label, randomised, controlled trial. Lancet Oncol. 2021 May;22(5):690-701. doi: 10.1016/S1470-2045(21)00027-9. Epub 2021 Mar 30. — View Citation

Liu QQ, Lin HM, Han HW, Yang CN, Liu C, Zhang R. Complete Response to Combined Chemotherapy and Anti-PD-1 Therapy for Recurrent Gallbladder Carcinosarcoma: A Case Report and Literature Review. Front Oncol. 2022 Mar 14;12:803454. doi: 10.3389/fonc.2022.803454. eCollection 2022. — View Citation

Morizane C, Okusaka T, Mizusawa J, Katayama H, Ueno M, Ikeda M, Ozaka M, Okano N, Sugimori K, Fukutomi A, Hara H, Mizuno N, Yanagimoto H, Wada K, Tobimatsu K, Yane K, Nakamori S, Yamaguchi H, Asagi A, Yukisawa S, Kojima Y, Kawabe K, Kawamoto Y, Sugimoto R, Iwai T, Nakamura K, Miyakawa H, Yamashita T, Hosokawa A, Ioka T, Kato N, Shioji K, Shimizu K, Nakagohri T, Kamata K, Ishii H, Furuse J; members of the Hepatobiliary and Pancreatic Oncology Group of the Japan Clinical Oncology Group (JCOG-HBPOG). Combination gemcitabine plus S-1 versus gemcitabine plus cisplatin for advanced/recurrent biliary tract cancer: the FUGA-BT (JCOG1113) randomized phase III clinical trial. Ann Oncol. 2019 Dec 1;30(12):1950-1958. doi: 10.1093/annonc/mdz402. — View Citation

Song X, Hu Y, Li Y, Shao R, Liu F, Liu Y. Overview of current targeted therapy in gallbladder cancer. Signal Transduct Target Ther. 2020 Oct 7;5(1):230. doi: 10.1038/s41392-020-00324-2. — View Citation

Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, Madhusudan S, Iveson T, Hughes S, Pereira SP, Roughton M, Bridgewater J; ABC-02 Trial Investigators. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010 Apr 8;362(14):1273-81. doi: 10.1056/NEJMoa0908721. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Radical resection rate	The proportion of patients whose tumors converted to a surgically resectable state and achieved radical resection within 8 courses of medication in all patients enrolled.	6 months
Secondary	Objective response rate (ORR)	Complete response (CR) and partial response (PR), at 6 months by RECIST v.1.1	6 months
Secondary	Disease control rate(DCR)	Complete response (CR) ,partial response (PR) and stable disease, SD, at 6 months by RECIST v.1.1	6 months
Secondary	Progression-free survival (PFS)	The time from first drug administration to the first documented disease progression according to RECIST version 1.1 or to death from any cause, whichever occurred first.	6 months
Secondary	Overall survival(OS)	The time from first drug administration to death from any cause.	6 months
Secondary	The incidence of treatment-related adverse event	Percentage of participants who experienced treatment-related adverse event	6 months