Study of Sirolimus in Patients With Advanced Pancreatic Cancer

NCT03662412 | Unknown Phase 1 DMC

• 1 other identifier: SAHZU-2018-064
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

Pancreatic cancer is a highly malignant tumor of the digestive system.In China, the annual mortality/morbidity of pancreatic cancer is as high as 0.88:1, and the morbidity and mortality are still on the rise. The 5-year survival rate of pancreatic cancer patients in the United States is only 8%, among which more than 50% of patients have distant metastasis at the time of diagnosis, and the 5-year survival rate of advanced patients with distant metastasis is as low as 3%, with extremely poor prognosis. Currently there is no standard treatment for the first - and second-line treatment resistant and postoperative recurrent patients to further prolong their survival. mammilian target of rapamycin (mTOR) is a very important serine/threonine protein kinase involved in the regulation of energy metabolism, cell growth, angiogenesis and other cellular biological processes.Rapamycin (sirolimus) is a selective inhibitor of mTOR kinase, which can inhibit the activation and proliferation of T lymphocytes to inhibit the immune response.Currently, mTOR inhibitors are also widely used in tumor treatment. Several studies have been performed to evaluate the efficacy of sirolimus in some solid tumors, and encouraging results are obtained. However, the existing studies on mTOR inhibitors and pancreatic cancer treatment are mostly phase I trials, with little evaluation of the efficacy. Therefore, the phase II clinical trial of rapamycin in the treatment of pancreatic cancer is very necessary. In preclinical studies, investigators found that rapamycin can effectively inhibit the angiogenesis of liver Cancer led by tumor-associated macrophages (TAM), thereby inhibiting the progression of liver Cancer.In vitro experiments on pancreatic cancer showed that rapamycin can directly inhibit the proliferation of pancreatic cancer cells.After the treatment with rapamycin in the homologous xenograft tumor model of mice, it was found that the tumor growth of mice was significantly inhibited. Further analysis suggested that rapamycin not only directly inhibits tumor proliferation, but also reverses the immune suppressive microenvironment of pancreatic cancer and promotes the T-cell-mediated anti-tumor immune response.Preclinical findings suggest that rapamycin may benefit survival in pancreatic cancer patients, which makes us very interested in the efficacy of rapamycin in patients with advanced pancreatic cancer.Therefore, investigators designed this trial to evaluate the clinical efficacy of rapamycin in patients with second-line resistance and recurrence who lacked a standard treatment regimen.

Conditions

Pancreatic Cancer

Outcome Measures

Primary Outcomes (1)

• overall survival

  The duration of time from patients begin with sirolimus treatment to the time of death or the end of the study.

  Up to approximately 24 months

Secondary Outcomes (1)

• Response rate

  Assessment performed at 6 months after the first treatment

Other Outcomes (2)

• Change of carbohydrate Antigen-199 (CA-199) level

  Up to 24 months, from 1 day before the first time treatment until date of first documented progression or date of death from any cause

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  Up to approximately 24 months

Study Arms (1)

Sirolimus treatment

EXPERIMENTAL

Oral solution of sirolimus, 2mg, once a day. The trial will be terminated when a serious adverse reaction occurred, or the tumor progressed rapidly twice in a row, or when the patient did not want to continue.

Drug: Sirolimus

Interventions

Sirolimus DRUG

Oral solution of sirolimus, 2mg, once a day.

Also known as: Rapamycin

Sirolimus treatment

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• patients who have failed second-line chemotherapy: patients who had previously received treatment with gemcitabine-based chemotherapy failed, and received fluorouracil based chemotherapy (such as FOLFIRINOX) and had received or not received radiotherapy and failed treatment.
• the Eastern Cooperative Oncology Group (ECOG) score is 0-1.
• subject's informed consent, understanding and willing to cooperate with the test program and sign relevant documents.

You may not qualify if:

• patients with other malignant tumors or pancreatic cancer have unclear clinical diagnosis, or there are some retroperitoneal lesions with other unclear properties.
• complicated with uncontrollable central nervous system metastases or neoplastic meningitis.
• complicated with serious and uncontrollable internal diseases such as severe diabetes, severe hypertension, serious infection, congestive heart failure, ventricular fibrillation, coronary heart disease with obvious symptoms or myocardial infarction in the past 6 months.
• patients with significant renal dysfunction (serum creatinine beyond the normal range).
• patients with significant abnormal liver function ( serum bilirubin \> 1.5 times or aspartate transaminase (AST)/aspartate transaminase (ALT) \> 2.5 times of the normal upper limit, \> 5 times of the normal upper limit if there is liver metastasis).
• patients with significantly abnormal white blood cell count (WBC) (neutrophils \< 1500 / mu or platelet \< 100 \* 10 \^ 3 L/mu L or hemoglobin \< 90 g/L).
• anesthesia, radiotherapy or systemic chemotherapy were performed within the past 2 weeks.
• drug maintenance: immunosuppressive drugs, and treatment dose of vitamin K antagonist.
• HIV patients.
• others: allergic history of similar drugs, pregnancy or lactation.

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead

Study Sites (1)

The second affiliated hospital of Zhejiang University

Hangzhou, Zhejiang, 310009, China

RECRUITING

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Tingbo Liang, MD Ph.D

  second affiliated hospital, Zhejiang University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Qi Zhang, MD

CONTACT

13819137113; zhangqi86@gmail.com

Yiwen Chen, MD

CONTACT

15088682641; cherry0705@126.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 20, 2018
• First Posted: September 7, 2018
• Study Start: June 1, 2018
• Primary Completion: June 30, 2023
• Study Completion: June 30, 2023
• Last Updated: September 7, 2018

Record last verified: 2018-09

Locations

CN (1)