SBRT and Anti-programmed Cell Death Protein 1(Anti-PD-1) in Late Stage or Recurrent Pancreatic Cancer Patients (CISPD-2)

Study on the Safety and Therapeutic Effect of Stereotactic Body Radiotherapy and Anti-PD-1 Antibody in Late Stage or Recurrent Pancreatic Cancer Patients Who Failed in Second-line Chemotherapy

When gemcitabine based chemo and fluorouracil based chemo regimes are failed in late-stage or recurrent pancreatic cancer patients, there is no alternative options. Anti-PD-1 antibody has became a promising anti-cancer drug. While it showed limited efficacy in pancreatic cancer. Stereotactic Body Radiotherapy has been a new method to locally treat metastatic cancer. This study is aimed to evaluate the safety and efficacy of the combination of SBRT and anti-PD-1 antibody in late-stage or recurrent pancreatic caner who failed in second-line chemotherapy.

Study Overview

• Status: Recruiting
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Radiation: SBRT; Drug: anti-PD-1 antibody

Detailed Description

Pancreatic cancer is a kind of cancer with poor prognosis. Nowadays, recommended treatment for late-stage or recurrent pancreatic cancer patients are fluorouracil based chemotherapy (such as FOLFIRINOX) and gemcitabine based chemotherapy. When these two chemo regimes are failed, however, there is no alternative options. With the improvement of immune therapy, anti-PD-1 antibody has became a promising anti-cancer drug. While it showed limited efficacy in pancreatic cancer. Stereotactic Body Radiotherapy (SBRT) has been a new method to locally treat metastatic cancer. And previous studies showed that SBRT may enhance the efficacy of immunotherapy. So this study is amed to evaluate the safety and efficacy of the combination of SBRT and anti-PD-1 antibody in late-stage or recurrent pancreatic caner who failed in second-line chemotherapy.

• Study Type: Interventional
• Enrollment (Anticipated): 36
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Yiwen Chen, MD; Phone Number: +8615088682641; Email: cherry0705@zju.edu.cn
• Study Contact Backup: Name: Qi Zhang, MD; Phone Number: +8613858108798; Email: zhangqi86@gmail.com

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Recruiting
      • The Second Affiliated Hospital of Zhejiang University
      • Contact: Yiwen Chen, MD; Phone Number: +8615088682641; Email: cherry0705@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 1.≥18 years.
• 2.Histopathology or cytology confirmed pancreatic cancer.
• 3.Patients failed in second-line chemotherapy: patients have failed in gemcitabine-based chemotherapy and also failed in fluorouracil-based chemotherapy (like FOLFIRINOX), failed in combination of chemotherapy and radiotherapy; patients may have failed in immune therapy (including anti-PD-1 antibody).
• 4. Eastern cooperative oncology group physical fitness score was 0~2.

• 5. The main organs are functional and meet the following criteria (Routine blood tests were in accordance with the following criteria):

  1. White blood cell (WBC) ≥3.5 x 10^6 /L, neutrophil >1.5 x10^9/L,
  2. platelet (PLT) ≥50 x10^9/L,
  3. hemoglobin (HB) ≥80 g/L,
  4. total bilirubin (TB) ≤1.5 x ULN (upper limit of normal value). 5）Alanine transaminase (ALT) and aspartate aminotransferase (AST) ≤ 2 x ULN (upper limit of normal value) (if there is liver metastasis, ≤ 5 x ULN).

  6) Serum creatinine (Scr) ≤ 1.5 x ULN 7) Albumin (ALB) ≥ 3 g/dL.

• 6. Patients will be informed consent, and understand and are willing to cooperate with the trial and sign related documents.

Exclusion Criteria:

• 1. In the first 4 weeks before the start of the study, they took part in other drug clinical trials.
• 2. Before the start of the study, they were diagnosed as immune deficiency diseases or need systemic steroid therapy.
• 3. In the first 4 weeks before the start of the study, they took anti-tumor immune therapy; or didn't recovery from the adverse effects caused by the anti-tumor immune therapy.
• 4. In the first 2 weeks before the start of the study, they took chemotherapy, small molecule targeting therapy, and radiotherapy; or didn't recovery from the adverse effects caused by these therapies.
• 5. Has had active tuberculosis before.
• 6. Has a history of malignant tumor, except for basal and skin squamous cell carcinoma, cervical carcinoma in situ and papillary thyroid carcinoma.
• 7. Has central nervous system metastasis or meningeal metastasis.
• 8. Has 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.
• 9. Has blood precancerous diseases, such as myelodysplastic syndrome.
• 10. Has clinically relevant or preexisting interstitial lung diseases, such as noncommunicable pneumonia or pulmonary fibrosis, or evidence of interstitial lung diseases on baseline chest CT scans or chest x-rays.
• 11. Past or physical examinations have found diseases of the central nervous system, with the exception of those that have been adequately treated (such as primary brain tumors, uncontrolled seizures or strokes with standard medication).
• 12. Has preexisting neuropathy at > level 1 (NCI CTCAE).
• 13. Allotransplantation requires immunosuppression therapy or other major immunosuppression therapy.
• 14. Has a severe open wound, ulcer, or fracture.
• 15. Systemic treatment is required for autoimmune diseases that have been active for the past 2 years.Alternative therapies are not systemic treatments.
• 16. Has a history of non-infectious pneumonia requiring steroid therapy or active pneumonia.Has interstitial lung disease.
• 17. Patients with active infections require systemic treatment.
• 18. Patients with active hepatitis b or c are not included in liver lesions SBRT.
• 19. Has vaccinate within 30 days before treatment.Including intranasal influenza vaccines, except seasonal influenza vaccines
• 20. Others: allergic history of similar drugs, pregnancy or lactation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: SBRT and PD-1; Stereotactic body radiotherapy, radiation dose is 40-50 Gy in total. Intravenous drug of anti-PD-1 antibody, 200mg, once a time, every three weeks.	Radiation: SBRT; SBRT radiation dose is 40-50 Gy in total.; Other Names: Stereotactic Body Radiotherapy; Drug: anti-PD-1 antibody; Intravenous drug of anti-PD-1 antibody, 200mg, once a time, every three weeks.; Other Names: keytruda

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival	The percentage of people still alive for a given period of time after diagnosis	Up to approximately 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease control rate	Percentage of patients whose cancer doesn't progress after treatment	Up to approximately 12 months
Objective response rate	Percentage of patients whose cancer shrinks or disappears after treatment	Up to approximately 12 months
Progression-free survival	The percentage of people does not get worse for a period of time after diagnosis	Up to approximately 12 months
Common Toxicity Criteria for Adverse Effects	According to Common Toxicity Criteria for Adverse Effects version 4	Up to approximately 12 months
EORTC quality of life questionnaire (QLQ)	Assessed by the European Organization for Research and Treatment of Cancer Quality of Life	Up to approximately 12 months
Related tumor markers	Serum level of related tumor markers (like carbohydrate antigen19-9, carcinoembryonic antigen and so on)	Up to approximately 12 months

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 22, 2018
• Primary Completion (ANTICIPATED): October 22, 2021
• Study Completion (ANTICIPATED): October 22, 2023

Study Registration Dates

• First Submitted: October 21, 2018
• First Submitted That Met QC Criteria: October 21, 2018
• First Posted (ACTUAL): October 23, 2018

Study Record Updates

• Last Update Posted (ACTUAL): November 6, 2018
• Last Update Submitted That Met QC Criteria: November 4, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: pancreatic cancer; Stereotactic Body Radiotherapy; immune therapy; Second-line Chemotherapy resistant
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Physiological Effects of Drugs; Immunologic Factors; Antibodies
• Other Study ID Numbers: CISPD-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No