Timing of Start of systemIc Treatment for Asymptomatic Metastasized Pancreatic Cancer (TIMEPAN)

May 18, 2021 updated by: J.W. Wilmink, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

TIming of Start of systemIc Treatment for Asymptomatic MEtastasized PANcreatic Cancer (TIMEPAN): a Randomized Controlled Multicenter Trial

Since patients with metastatic pancreatic cancer have a limited life expectancy, it is important to determine the timing of when to start chemotherapy in order to optimize the benefits of chemotherapy relative to the side effects. Therefore, two treatment strategies can be considered: chemotherapy started immediately at diagnosis, or delayed until disease-related symptoms occur.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

184

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Netherlands
    • Noord-Holland
      • Amsterdam, Noord-Holland, Netherlands, 1105AZ

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  • Signed, written Institutional Review Board/Ethics Committee-approved Informed Consent Form (ICF).
  • Patients with histologically/cytological confirmed diagnosis of metastatic pancreatic ductal adenocarcinoma.
  • Measurable disease on computed tomography (CT) scan per RECIST version 1.1 criteria.
  • Eastern Cooperative Oncology Group Performance Status of 0-1
  • Life expectancy ≥ 3 months.
  • Age ≥ 18 years.
  • A negative urine or serum pregnancy test within 7 days before Day 1 (first dose of study medication) if female subject is of childbearing potential.

  • Screening clinical laboratory values as follows:

    1. Absolute neutrophil count > 1.5 x 109 /L
    2. Total bilirubin ≤ 1.5 times upper limit of normal (ULN).
    3. Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 times ULN, (if liver metastases are present, then ≤ 5 times ULN is allowed).
    4. Serum creatinine < 1.5 x ULN or creatinine clearance >50 mL/min/1.73 m2
    5. Prothrombin time/international normalized ratio within normal limits (± 15%) or within therapeutic range if subject takes warfarin. Partial thromboplastin time (PTT) within normal limits (± 15%).
    6. Platelet count > 100,000 x 109 /L

  • No symptoms related to advanced disease, specified as:

    1. no pain requiring regular narcotic analgesics;
    2. no weight loss over 5 kg (unless related to surgery or other illness);
    3. no persistent nausea requiring medication;
    4. no obstructive bowel symptoms;
    5. no persistent fever related to metastatic cancer;
    6. no other symptom which in the opinion of the clinician was due to progressive metastatic cancer.
  • No prior chemotherapy for metastatic disease (patients might have received adjuvant treatment more than 6 months before the development of metastatic disease, or neoadjuvant treatment before surgery for resectable disease)

Exclusion Criteria:

  • Known central nervous system involvement or brain metastases.
  • New York Heart Association Class III or IV cardiac disease or myocardial infarction within the past 12 months
  • Any other disease, active, uncontrolled bacterial, viral or fungal infection requiring systemic therapy, metabolic dysfunction, physical examination finding or clinical laboratory finding that leads to reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, that may affect the interpretation of the results, or that may render the subject at high risk for treatment complications.
  • Inability to comply with study and follow-up procedures as judged by the Investigator.
  • Women currently pregnant or breastfeeding.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: Immediate treatment
The treatment schedule will be direct (start within 3 weeks of bate of diagnosis) FOLFIRINOX or nab paclitaxel in combination with gemcitabine per investigator's choice. Dosage and frequency of administration will be according to local protocol.
Drug: Folfirinox
In both arms the intervention will be FOLRINIOX or nab paclitaxel in combination with gemcitabine per investigator's choice
ACTIVE_COMPARATOR: Delayed treatment

The treatment schedule will be delayed treatment (based on symptoms) with FOLFIRINOX or nab paclitaxel in combination with gemcitabine per investigator's choice. Dosage and frequency of administration will be according to local protocol.

Chemotherapy will start as soon as one of the following criteria is met:

  • Decline in performance status to ECOG < 1 or Karnofsky < 80%
  • Weight loss more than 5% of the total body weight from the time of study entry
  • Persistent nausea requiring medication
  • Pain requiring regular narcotic analgesics
  • Development of clinically significant third-space fluid collections
  • Liver function deterioration in the presence of progressive liver metastases
Drug: Folfirinox
In both arms the intervention will be FOLRINIOX or nab paclitaxel in combination with gemcitabine per investigator's choice

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Quality adjusted overall survival
Time Frame: From date of randomization until the date of death, assessed up to 12 months
Measured in "utility-per-month", using the survival in months and the monthly reported quality of life by the EQ-5D-5L questionaire.
From date of randomization until the date of death, assessed up to 12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to disease progression
Time Frame: 12 months
Restricted mean progression free survival (RM-PFS): are under the Kaplan-Meier PFS curve between randomization and follow-up of the study (estimated 12 months)
12 months
Quality adjusted progression free survival (PFS)
Time Frame: From date of randomization until the date of death, assessed up to 12 months
From date of randomization until the date of death, assessed up to 12 months
Duration of time without symptoms of disease progression or toxicities (TWiST)
Time Frame: From date of randomization until the date of death, assessed up to 12 months
From date of randomization until the date of death, assessed up to 12 months
Overall survival
Time Frame: From date of randomization until the date of death, assessed up to 12 months
(In months)
From date of randomization until the date of death, assessed up to 12 months
Number of patients with adverse events
Time Frame: From date of randomization until the date of death, assessed up to 12 months
According to NCI CTC version 5.0
From date of randomization until the date of death, assessed up to 12 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Level of CA 19.9
Time Frame: From date of randomization until the date of death, assessed up to 12 months
Exploratory endpoint
From date of randomization until the date of death, assessed up to 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

April 22, 2021

Primary Completion (ANTICIPATED)

April 22, 2024

Study Completion (ANTICIPATED)

April 22, 2024

Study Registration Dates

First Submitted

May 7, 2021

First Submitted That Met QC Criteria

May 18, 2021

First Posted (ACTUAL)

May 24, 2021

Study Record Updates

Last Update Posted (ACTUAL)

May 24, 2021

Last Update Submitted That Met QC Criteria

May 18, 2021

Last Verified

May 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NL722253.018.19

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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