An Open-label, Phase I/II Study of PLENA Regimen in Patients With Unresectable Pancreatic Cancer or BTC

A Phase I/II, Open-label, One-arm, Single-center Study to Evaluate the Safety and Efficacy of the PLENA Regimen in Subjects With Unresectable Pancreatic Cancer or Biliary Tract Cancer

Immunotherapy of cancer based on PD-1/PD-L1 blockade has prompted a revolution in cancer clinical management, albeit as yet immunotherapy-based treatment approaches in pancreatic cancer and biliary tract cancer (BTC) remain to have proven value, highlights the urgency for designing novel therapeutic strategies to combat these deadly diseases. The immunomodulatory effect of lenvatinib (Lenvatinib is an oral multi-kinase inhibitor) on tumor microenvironments may contribute to antitumor activity of immune checkpoint blockade. This one-arm, phase I/II study is designed to assess the safety and efficacy of the combined regimen of Durvalumab (anti-PD-L1 antibody), Lenvatinib and Paclitaxel albumin (nab-paclitaxel).

Study Overview

• Status: Recruiting
• Conditions: Pancreatic Cancer; Biliary Tract Cancer
• Intervention / Treatment: Drug: Durvalumab; Drug: Lenvatinib; Drug: Nab paclitaxel

• Study Type: Interventional
• Enrollment (Anticipated): 65
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Weidong Han; Phone Number: +861066937463; Email: hanwdrsw@sina.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100083
      • Recruiting
      • Biotherapeutic Department of Chinese PLA General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1.Subjects must have histologically proven unresectable pancreatic cancer or biliary tract cancer 2.18 to 75 years old. 3.Life expectancy of at least 6 months. 4.Eastern Cooperative Oncology Group performance status 0-2. 5.Subjects must have at least one measurable lesion ≥ 1 cm as defined by response criteria.

6.Subjects with Anti-PD-1/L1 antibody treatment history are eligible which must be disease progression.

7.Adequate organ function. 8.Participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study drug.

Exclusion Criteria:

1. Subjects with any autoimmune disease or history of syndrome that requires corticosteroids or immunosuppressive medications.
2. Serious uncontrolled medical disorders or active infections, pulmonary infection especially.
3. Prior organ allograft.
4. Women who are pregnant or breastfeeding.
5. Women with a positive pregnancy test on enrollment or prior to investigational product administration.
6. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PLENA regimen; Subject received PLENA regimen every 3 weeks until achieving a second assessable complete response or up to a maximum of 8 cycles. Treatment continued until progressive disease or intolerable toxicity, or withdrawal of consent.	Drug: Durvalumab; Administered intravenously, 1000 mg on day 1 in a 3-week cycle; Drug: Lenvatinib; Administered orally, 8mg/d once daily in a 3-week cycle; Drug: Nab paclitaxel; Administered intravenously, 180-220 mg/m2 on day1 in a 3-week cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects with treatment-related adverse events (AEs)	Incidence, nature, and severity of adverse events graded according to the NCI CTCAE v5.0. AEs were considered to be treatment-related if they had started or worsened within the interval from first study drug administration until the follow-up visit.	6 months
Object response rate (ORR)	ORR is defined as the proportion of subjects who achieved a partial response (PR) or complete response (CR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease control rate (DCR)	DCR is defined as the proportion of subjects who achieved a stable disease (SD), partial response (PR) or complete response (CR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.	12 months
Progression-free survival (PFS)	PFS time was measured from study entry to the first documentation of disease progression or death. Disease progression was determined per the RECIST V1.1.	12 months
Overall survival (OS)	OS time was measured from the study entry to the date of death.	24 months
Number of participants with laboratory test abnormalities	The laboratory tests of serum cytokines and chemokines will be performed on day 1 of each cycle, and the abnormality will be determined by the investigator.	12 months

Collaborators and Investigators

• Sponsor: Chinese PLA General Hospital
• Investigators: Principal Investigator: Weidong Han, Dr, Chinese PLA General Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): April 12, 2022
• Primary Completion (Anticipated): April 30, 2023
• Study Completion (Anticipated): April 30, 2024

Study Registration Dates

• First Submitted: April 7, 2022
• First Submitted That Met QC Criteria: April 7, 2022
• First Posted (Actual): April 14, 2022

Study Record Updates

• Last Update Posted (Actual): April 14, 2022
• Last Update Submitted That Met QC Criteria: April 7, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: nab-paclitaxel; lenvatinib; unresectable; anti-PD-L1 antibody
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Biliary Tract Diseases; Pancreatic Diseases; Pancreatic Neoplasms; Biliary Tract Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Protein Kinase Inhibitors; Paclitaxel; Durvalumab; Lenvatinib
• Other Study ID Numbers: CHN-PLAGH-BT-070

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