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

NCT ID: NCT05919095

Last Updated: 2023-06-26

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 37 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-06-30
• Study Completion Date: 2026-06-30

Brief 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.

Detailed 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.

Conditions

Unresectable Gallbladder Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Carrilizumab plus GEMOX

Carrilizumab combinated With gemcitabine and oxaliplatin (GEMOX)

Group Type: EXPERIMENTAL

Carrilizumab plus GEMOX

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Rui Zhang, PhD

Role: PRINCIPAL_INVESTIGATOR

Department of Biliary and Pancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University

Locations

Sun Yat-sen Memorial Hospital, Sun Yat-sen University

Guangzhou, Guangdong, China

Countries

China

Central Contacts

Rui Zhang, PhD

Role: CONTACT

zhangr95@mail.sysu.edu.cn

020-34078840

Yanfang Ye

Role: CONTACT

yeyfang@mail.sysu.edu.cn

020-81336505

References

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

Reference Type: BACKGROUND

PMID: 30264121 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 33798493 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 33028805 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 20375404 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 31566666 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 33172881 (View on PubMed)

Creasy JM, Goldman DA, Dudeja V, Lowery MA, Cercek A, Balachandran VP, Allen PJ, DeMatteo RP, Kingham PT, 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.

Reference Type: BACKGROUND

PMID: 28216422 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 29706425 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 26240009 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 35372010 (View on PubMed)

Other Identifiers

SYSKY-2022-516-02

Identifier Type: -

Identifier Source: org_study_id