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

Primary Purpose

Metastatic Pancreas Cancer

Status
Recruiting
Phase
Phase 3
Locations
Netherlands
Study Type
Interventional
Intervention
Folfirinox
Sponsored by
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Pancreas Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Academic Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Immediate treatment

Delayed treatment

Arm Description

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.

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

Outcomes

Primary Outcome Measures

Quality adjusted overall survival
Measured in "utility-per-month", using the survival in months and the monthly reported quality of life by the EQ-5D-5L questionaire.

Secondary Outcome Measures

Time to disease progression
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)
Quality adjusted progression free survival (PFS)
Duration of time without symptoms of disease progression or toxicities (TWiST)
Overall survival
(In months)
Number of patients with adverse events
According to NCI CTC version 5.0

Full Information

First Posted
May 7, 2021
Last Updated
May 18, 2021
Sponsor
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
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1. Study Identification

Unique Protocol Identification Number
NCT04897854
Brief Title
Timing of Start of systemIc Treatment for Asymptomatic Metastasized Pancreatic Cancer
Acronym
TIMEPAN
Official Title
TIming of Start of systemIc Treatment for Asymptomatic MEtastasized PANcreatic Cancer (TIMEPAN): a Randomized Controlled Multicenter Trial
Study Type
Interventional

2. Study Status

Record Verification Date
May 2021
Overall Recruitment Status
Recruiting
Study Start Date
April 22, 2021 (Actual)
Primary Completion Date
April 22, 2024 (Anticipated)
Study Completion Date
April 22, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Pancreas Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
184 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Immediate treatment
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Delayed treatment
Arm Type
Active Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Folfirinox
Intervention Description
In both arms the intervention will be FOLRINIOX or nab paclitaxel in combination with gemcitabine per investigator's choice
Primary Outcome Measure Information:
Title
Quality adjusted overall survival
Description
Measured in "utility-per-month", using the survival in months and the monthly reported quality of life by the EQ-5D-5L questionaire.
Time Frame
From date of randomization until the date of death, assessed up to 12 months
Secondary Outcome Measure Information:
Title
Time to disease progression
Description
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)
Time Frame
12 months
Title
Quality adjusted progression free survival (PFS)
Time Frame
From date of randomization until the date of death, assessed up to 12 months
Title
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
Title
Overall survival
Description
(In months)
Time Frame
From date of randomization until the date of death, assessed up to 12 months
Title
Number of patients with adverse events
Description
According to NCI CTC version 5.0
Time Frame
From date of randomization until the date of death, assessed up to 12 months
Other Pre-specified Outcome Measures:
Title
Level of CA 19.9
Description
Exploratory endpoint
Time Frame
From date of randomization until the date of death, assessed up to 12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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: Absolute neutrophil count > 1.5 x 109 /L Total bilirubin ≤ 1.5 times upper limit of normal (ULN). Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 times ULN, (if liver metastases are present, then ≤ 5 times ULN is allowed). Serum creatinine < 1.5 x ULN or creatinine clearance >50 mL/min/1.73 m2 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%). Platelet count > 100,000 x 109 /L No symptoms related to advanced disease, specified as: no pain requiring regular narcotic analgesics; no weight loss over 5 kg (unless related to surgery or other illness); no persistent nausea requiring medication; no obstructive bowel symptoms; no persistent fever related to metastatic cancer; 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
J.W. Wilmink, Dr.
Phone
+31 20 5628065
Email
j.w.wilmink@amsterdamumc.nl
First Name & Middle Initial & Last Name or Official Title & Degree
S. Augustinus
Email
s.augustinus@amsterdamumc.nl
Facility Information:
Facility Name
Academic Medical Center
City
Amsterdam
State/Province
Noord-Holland
ZIP/Postal Code
1105AZ
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
J.W. Wilmink, Dr.
Phone
+31 20 5628065
Email
j.w.wilmink@amsterdamumc.nl

12. IPD Sharing Statement

Plan to Share IPD
No

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Timing of Start of systemIc Treatment for Asymptomatic Metastasized Pancreatic Cancer

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