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Quality of Life in Locally Advanced or Metastatic Pancreatic Cancer Treated With Gemcitabine and Nab-paclitaxel (QOLINPAC)

Primary Purpose

Pancreatic Cancer

Status
Completed
Phase
Phase 2
Locations
Belgium
Study Type
Interventional
Intervention
Nab-paclitaxel
Gemcitabine
Sponsored by
Universitaire Ziekenhuizen KU Leuven
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pancreatic Cancer focused on measuring Pancreatic cancer, Locally advanced, Metastatic

Eligibility Criteria

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

Inclusion Criteria:

  • Written informed consent (+ optional for TR) must be given according to ICH/GCP and national/local regulations.
  • Patient is at least 18 years of age .
  • Unresectable locally advanced or metastatic pancreatic cancer.
  • Histologically or cytologically confirmed adenocarcinoma of the pancreas. Islet cell neoplasms are excluded.
  • Evaluable or measurable disease, not in a previously irradiated area.
  • Life expectancy of at least 12 weeks.
  • WHO ECOG performance status ≤ 2
  • Adequate organ function.
  • Adequate bone marrow, hepatic and renal function. Acceptable coagulation (prothrombin time and partial thromboplastin time within +/- 15% of normal limits).
  • No clinically significant abnormalities in urinalysis.
  • Effective contraception for both male and female patients if applicable. Women of childbearing potential must have negative blood pregnancy test at screening visit.

Exclusion criteria:

  • Prior chemotherapy, radiotherapy, surgery or other investigational therapy for the treatment for metastatic disease. Adjuvant treatment with gemcitabine or 5-FU is allowed provided at least 6 months have elapsed since completion of the last dose.
  • Major surgery within 4 weeks of the start of the study.
  • Irradiation within 3 weeks prior to study entry.
  • Brain metastasis (known or suspected).
  • Serious medical risk factors involving any of the major organ systems, including high cardiovascular risk including coronary stenting or myocardial infarction in the last year and psychiatric disorders.
  • Historical or active infection with HIV, hepatitis B or C.
  • History of connective tissue disorders (eg. lupus, scleroderma, arteritis nodosa, etc).
  • History of interstitial lung disease.
  • History of peripheral artery disease.
  • Previous (within 5 years) or concurrent malignancies at other sites with the exception of surgically cured or adequately treated carcinoma in-situ of the cervix and basal cell carcinoma of the skin.
  • Known allergy or any other adverse reaction to any of the drugs or to any related compound.
  • Use of Coumadin.
  • Organ allografts requiring immunosuppressive therapy.
  • Pregnancy or breast-feeding.
  • Medical, social or psychological condition which, in the opinion of the investigator, would not permit the patient to complete the study or sign meaningful informed consent.

Sites / Locations

  • OLV Ziekenhuis Aalst
  • AZ Klina
  • AZ St Lucas
  • ULB Hôpital Erasme
  • Cliniques Universitaires St Luc
  • CHU de Charleroi
  • UZ Antwerpen
  • AZ Maria Middelares
  • UZ Gent
  • UZ Leuven
  • CHC St Joseph
  • CHR Citadelle
  • CHU Sart-Tilman
  • Heilig Hartziekenhuis Lier
  • AZ Sint Maarten
  • Clinique St Elisabeth
  • AZ Delta
  • AZ Turnhout

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Arm A

Arm B

Arm Description

Nab-paclitaxel - IV - 125 mg/m2 - 3xq4wks Gemcitabine - IV - 1000 mg/m2 - 3xq4wks

Gemcitabine - IV - 1000 mg/m2 - 3xq4wks

Outcomes

Primary Outcome Measures

Deterioration-free Survival Rate of the QOL Global Health Status at 3, 6 and 12 Months (Mos)
The QOL global health status (GHS) is a functional parameter derived from the EORTC QLQ - C30 questionnaire, based on questions 29 "How would you rate your overall health during the past week?" and 30 "How would you rate your overall quality of life during the past week?". Transformed scores range from 0 to 100% with higher scores representing better outcomes. The deterioration free survival rate at 3 mos is defined as the Kaplan-Meier estimate of the probability of being alive and free of deterioration of the QOL score at 3 mos. The definitive deterioration of the QOL score is a decrease of at least 10 points (minimal clinical important difference) as compared to baseline, with no further improvement of more than 10 points as compared to the score qualifying the deterioration or with no data after deterioration. Death was also considered as an event if the patient did not experience deterioration before death. Patients without event were censored at the time of last follow-up.
QOL Global Health Status Deterioration-free Median Survival
The deterioration-free survival is defined as the Kaplan-Meier estimate of median survival time to definitive deterioration of the QOL score or death. See primary outcome 1 for scale description. The definitive deterioration of the QOL score is a decrease of at least 10 points (minimal clinical important difference) as compared to the baseline score, with no further improvement of more than 10 points as compared to the score qualifying the deterioration or with no data after the deterioration was observed. Death was also considered as an event if the patient did not experience deterioration before death. Patients without event were censored at the time of last follow-up.

Secondary Outcome Measures

Overall Response
Tumour response was assessed locally based on radiological assessments (CT/MRI) of target and nontarget lesions and considering the occurrence of new lesions, as per RECIST criteria. Tumour response was defined at each evaluation as complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD). Best response during treatment was selected for each patient. Overall response (OR) is defined as the best tumor response on treatment for each patient. Responders were considered CR + PR. Some patients were not evaluable for response (no scans available). Overall response rates (ORR) were calculated based on the ITT set.
Duration of Response (in Responders)
Duration of response was calculated from the date of first documented response to the date of progression (including SD after PR) or date of start of new treatment in not progressed, when available. In 2 patients with CR, periods of PR are included. For those not documented as progressed before death, an unknown duration was kept and considered missing data.
Disease Control
Tumour response was assessed locally based on radiological assessments (CT/MRI) of target and nontarget lesions and considering the occurrence of new lesions, as per RECIST criteria. Tumour response was defined at each evaluation as complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD). Best response during treatment was selected for each patient. Overall response is defined as the best tumor response on treatment for each patient. Disease control is defined as a best response on treatment of either CR, PR or SD (CR + PR + SD). Some patients were not evaluable for response (no scans available). Overall response rates were calculated based on the ITT set.
Progression Free Survival
Progression free survival time was considered from start of treatment until the first observation of disease progression or death from any cause, whichever occurred first. All patients (ITT).
Overall Survival
Overall survival was considered from start of treatment to death. All patients (ITT)
Laboratory Safety Assessment
Severe laboratory abnormalities (hematology and biochemistry grade 3 and higher). Worst grade per patient. All patients treated (Safety set).

Full Information

First Posted
January 21, 2014
Last Updated
October 24, 2019
Sponsor
Universitaire Ziekenhuizen KU Leuven
Collaborators
Celgene Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT02106884
Brief Title
Quality of Life in Locally Advanced or Metastatic Pancreatic Cancer Treated With Gemcitabine and Nab-paclitaxel
Acronym
QOLINPAC
Official Title
Randomized Crossover Trial to Assess the Effects and Quality of Life in Patients With Locally Advanced or Metastatic Pancreatic Cancer Treated With Gemcitabine in Combination With Nab-paclitaxel: QOLINPAC
Study Type
Interventional

2. Study Status

Record Verification Date
October 2019
Overall Recruitment Status
Completed
Study Start Date
April 2014 (Actual)
Primary Completion Date
April 29, 2019 (Actual)
Study Completion Date
April 29, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Universitaire Ziekenhuizen KU Leuven
Collaborators
Celgene Corporation

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This was a quality of life (QOL) study done in the context of a randomized trial in locally advanced or metastatic pancreatic cancer. Eligible patients were randomized to receive either the combination of nab-paclitaxel/gemcitabine or standard gemcitabine monotherapy. The combination regimen of nab-paclitaxel and gemcitabine showed improved efficacy with acceptable toxicity in this disease setting in first-line and was approved for this indication. The study design allowed patients in standard treatment to receive the combination treatment after first tumour progression. The proposed study explored the impact of treatment on the QOL scores and compared the times to definitive deterioration of the QOL scores using the validated EORTC QLQ-C30 questionnaire. Efficacy and safety were secondary endpoints and were reported descriptively. Molecular studies will be performed on blood and tissue samples as avaialble and will be reported separately.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Cancer
Keywords
Pancreatic cancer, Locally advanced, Metastatic

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
146 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm A
Arm Type
Experimental
Arm Description
Nab-paclitaxel - IV - 125 mg/m2 - 3xq4wks Gemcitabine - IV - 1000 mg/m2 - 3xq4wks
Arm Title
Arm B
Arm Type
Active Comparator
Arm Description
Gemcitabine - IV - 1000 mg/m2 - 3xq4wks
Intervention Type
Drug
Intervention Name(s)
Nab-paclitaxel
Other Intervention Name(s)
Abraxane, EU/1/07/428/001, L01CD01
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Other Intervention Name(s)
Gemzar
Primary Outcome Measure Information:
Title
Deterioration-free Survival Rate of the QOL Global Health Status at 3, 6 and 12 Months (Mos)
Description
The QOL global health status (GHS) is a functional parameter derived from the EORTC QLQ - C30 questionnaire, based on questions 29 "How would you rate your overall health during the past week?" and 30 "How would you rate your overall quality of life during the past week?". Transformed scores range from 0 to 100% with higher scores representing better outcomes. The deterioration free survival rate at 3 mos is defined as the Kaplan-Meier estimate of the probability of being alive and free of deterioration of the QOL score at 3 mos. The definitive deterioration of the QOL score is a decrease of at least 10 points (minimal clinical important difference) as compared to baseline, with no further improvement of more than 10 points as compared to the score qualifying the deterioration or with no data after deterioration. Death was also considered as an event if the patient did not experience deterioration before death. Patients without event were censored at the time of last follow-up.
Time Frame
From date of randomisation to 3, 6 and 12 months respectively
Title
QOL Global Health Status Deterioration-free Median Survival
Description
The deterioration-free survival is defined as the Kaplan-Meier estimate of median survival time to definitive deterioration of the QOL score or death. See primary outcome 1 for scale description. The definitive deterioration of the QOL score is a decrease of at least 10 points (minimal clinical important difference) as compared to the baseline score, with no further improvement of more than 10 points as compared to the score qualifying the deterioration or with no data after the deterioration was observed. Death was also considered as an event if the patient did not experience deterioration before death. Patients without event were censored at the time of last follow-up.
Time Frame
From date of randomisation to end of follow up (max 3 years after database lock when applicable).
Secondary Outcome Measure Information:
Title
Overall Response
Description
Tumour response was assessed locally based on radiological assessments (CT/MRI) of target and nontarget lesions and considering the occurrence of new lesions, as per RECIST criteria. Tumour response was defined at each evaluation as complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD). Best response during treatment was selected for each patient. Overall response (OR) is defined as the best tumor response on treatment for each patient. Responders were considered CR + PR. Some patients were not evaluable for response (no scans available). Overall response rates (ORR) were calculated based on the ITT set.
Time Frame
Measured during treatment and FU, from signature of informed consent to progression (variable for each patient), for a max of 3 years from database lock (when applicable).
Title
Duration of Response (in Responders)
Description
Duration of response was calculated from the date of first documented response to the date of progression (including SD after PR) or date of start of new treatment in not progressed, when available. In 2 patients with CR, periods of PR are included. For those not documented as progressed before death, an unknown duration was kept and considered missing data.
Time Frame
Measured during treatment and FU, from signature of informed consent to progression (variable for each patient), for a max of 3 years from database lock (when applicable).
Title
Disease Control
Description
Tumour response was assessed locally based on radiological assessments (CT/MRI) of target and nontarget lesions and considering the occurrence of new lesions, as per RECIST criteria. Tumour response was defined at each evaluation as complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD). Best response during treatment was selected for each patient. Overall response is defined as the best tumor response on treatment for each patient. Disease control is defined as a best response on treatment of either CR, PR or SD (CR + PR + SD). Some patients were not evaluable for response (no scans available). Overall response rates were calculated based on the ITT set.
Time Frame
Measured during treatment and FU, from signature of informed consent to progression (variable for each patient), for a max of 3 years from database lock (when applicable).
Title
Progression Free Survival
Description
Progression free survival time was considered from start of treatment until the first observation of disease progression or death from any cause, whichever occurred first. All patients (ITT).
Time Frame
Measured during treatment and FU, from signature of informed consent to progression (variable for each patient), for a max of 3 years from database lock (when applicable).
Title
Overall Survival
Description
Overall survival was considered from start of treatment to death. All patients (ITT)
Time Frame
Measured during treatment and FU, from signature of informed consent to progression (variable for each patient), for a max of 3 years from database lock (when applicable).
Title
Laboratory Safety Assessment
Description
Severe laboratory abnormalities (hematology and biochemistry grade 3 and higher). Worst grade per patient. All patients treated (Safety set).
Time Frame
Measured during treatment, from signature of informed consent to end of treatment, plus 30 days mandatory safety follow-up period. Duration of treatment was variable for each patient.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Written informed consent (+ optional for TR) must be given according to ICH/GCP and national/local regulations. Patient is at least 18 years of age . Unresectable locally advanced or metastatic pancreatic cancer. Histologically or cytologically confirmed adenocarcinoma of the pancreas. Islet cell neoplasms are excluded. Evaluable or measurable disease, not in a previously irradiated area. Life expectancy of at least 12 weeks. WHO ECOG performance status ≤ 2 Adequate organ function. Adequate bone marrow, hepatic and renal function. Acceptable coagulation (prothrombin time and partial thromboplastin time within +/- 15% of normal limits). No clinically significant abnormalities in urinalysis. Effective contraception for both male and female patients if applicable. Women of childbearing potential must have negative blood pregnancy test at screening visit. Exclusion criteria: Prior chemotherapy, radiotherapy, surgery or other investigational therapy for the treatment for metastatic disease. Adjuvant treatment with gemcitabine or 5-FU is allowed provided at least 6 months have elapsed since completion of the last dose. Major surgery within 4 weeks of the start of the study. Irradiation within 3 weeks prior to study entry. Brain metastasis (known or suspected). Serious medical risk factors involving any of the major organ systems, including high cardiovascular risk including coronary stenting or myocardial infarction in the last year and psychiatric disorders. Historical or active infection with HIV, hepatitis B or C. History of connective tissue disorders (eg. lupus, scleroderma, arteritis nodosa, etc). History of interstitial lung disease. History of peripheral artery disease. Previous (within 5 years) or concurrent malignancies at other sites with the exception of surgically cured or adequately treated carcinoma in-situ of the cervix and basal cell carcinoma of the skin. Known allergy or any other adverse reaction to any of the drugs or to any related compound. Use of Coumadin. Organ allografts requiring immunosuppressive therapy. Pregnancy or breast-feeding. Medical, social or psychological condition which, in the opinion of the investigator, would not permit the patient to complete the study or sign meaningful informed consent.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eric Van Cutsem, MD
Organizational Affiliation
UZ Leuven
Official's Role
Principal Investigator
Facility Information:
Facility Name
OLV Ziekenhuis Aalst
City
Aalst
ZIP/Postal Code
9300
Country
Belgium
Facility Name
AZ Klina
City
Brasschaat
ZIP/Postal Code
2930
Country
Belgium
Facility Name
AZ St Lucas
City
Brugge
ZIP/Postal Code
8310
Country
Belgium
Facility Name
ULB Hôpital Erasme
City
Brussels
ZIP/Postal Code
1070
Country
Belgium
Facility Name
Cliniques Universitaires St Luc
City
Brussels
ZIP/Postal Code
1200
Country
Belgium
Facility Name
CHU de Charleroi
City
Charleroi
ZIP/Postal Code
6110
Country
Belgium
Facility Name
UZ Antwerpen
City
Edegem
ZIP/Postal Code
2650
Country
Belgium
Facility Name
AZ Maria Middelares
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
UZ Gent
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
UZ Leuven
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
CHC St Joseph
City
Liege
ZIP/Postal Code
4000
Country
Belgium
Facility Name
CHR Citadelle
City
Liege
ZIP/Postal Code
4000
Country
Belgium
Facility Name
CHU Sart-Tilman
City
Liege
ZIP/Postal Code
4000
Country
Belgium
Facility Name
Heilig Hartziekenhuis Lier
City
Lier
ZIP/Postal Code
2500
Country
Belgium
Facility Name
AZ Sint Maarten
City
Mechelen
ZIP/Postal Code
2800
Country
Belgium
Facility Name
Clinique St Elisabeth
City
Namur
ZIP/Postal Code
5000
Country
Belgium
Facility Name
AZ Delta
City
Roeselare
Country
Belgium
Facility Name
AZ Turnhout
City
Turnhout
ZIP/Postal Code
2300
Country
Belgium

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
http://www.ncbi.nlm.nih.gov/pubmed/8433390
Description
The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology.
URL
http://www.ncbi.nlm.nih.gov/pubmed/25436122
Description
Quality-of-life (QoL) as a predictive biomarker in patients with advanced pancreatic cancer (APC) receiving chemotherapy: results from a prospective multicenter phase 2 trial.
URL
http://www.ncbi.nlm.nih.gov/pubmed/20724140
Description
Time until definitive quality of life score deterioration as a means of longitudinal analysis for treatment trials in patients with metastatic pancreatic adenocarcinoma.
URL
http://www.ncbi.nlm.nih.gov/pubmed/26185420
Description
Pancreatic cancer: optimizing treatment options, new, and emerging targeted therapies.
URL
http://www.ncbi.nlm.nih.gov/pubmed/18599286
Description
Quality, interpretation and presentation of European Organisation for Research and Treatment of Cancer quality of life questionnaire core 30 data in randomised controlled trials
URL
http://www.ncbi.nlm.nih.gov/pubmed/21561347
Description
FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer
URL
http://www.ncbi.nlm.nih.gov/pubmed/25638248
Description
nab-Paclitaxel plus gemcitabine for metastatic pancreatic cancer: long-term survival from a phase III trial.
URL
http://www.ncbi.nlm.nih.gov/pubmed/23213101
Description
Impact of FOLFIRINOX compared with gemcitabine on quality of life in patients with metastatic pancreatic cancer: results from the PRODIGE 4/ACCORD 11 randomized trial.
URL
http://www.ncbi.nlm.nih.gov/pubmed/20886240
Description
Minimal important differences for interpreting health-related quality of life scores from the EORTC QLQ-C30 in lung cancer patients participating in randomized controlled trials.
URL
http://www.ncbi.nlm.nih.gov/pubmed/20030832
Description
Quality of life data as prognostic indicators of survival in cancer patients: an overview of the literature from 1982 to 2008.
URL
http://www.ncbi.nlm.nih.gov/pubmed/27914467
Description
Impact of the occurrence of a response shift on the determination of the minimal important difference in a health-related quality of life score over time.
URL
http://www.ncbi.nlm.nih.gov/pubmed/19695956
Description
Baseline quality of life as a prognostic indicator of survival: a meta-analysis of individual patient data from EORTC clinical trials.
URL
http://www.ncbi.nlm.nih.gov/pubmed/24127333
Description
A global analysis of multitrial data investigating quality of life and symptoms as prognostic factors for survival in different tumor sites.
URL
http://www.ncbi.nlm.nih.gov/pubmed/25207767
Description
Pancreatic adenocarcinoma.
URL
http://www.ncbi.nlm.nih.gov/pubmed/27247222
Description
Metastatic Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline
URL
http://www.ncbi.nlm.nih.gov/pubmed/28399388
Description
Metastatic Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline Summary.Metastatic Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline Summary.
URL
http://www.ncbi.nlm.nih.gov/pubmed/21969517
Description
Gemcitabine plus nab-paclitaxel is an active regimen in patients with advanced pancreatic cancer: a phase I/II trial.
URL
http://www.ncbi.nlm.nih.gov/pubmed/24131140
Description
Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine.
URL
http://www.ncbi.nlm.nih.gov/pubmed/29791286
Description
Metastatic Pancreatic Cancer: ASCO Clinical Practice Guideline Update.
URL
http://www.ncbi.nlm.nih.gov/pubmed/25311306
Description
Joint modeling of longitudinal health-related quality of life data and survival
URL
http://www.ncbi.nlm.nih.gov/pubmed/24902940
Description
Longitudinal quality of life data: a comparison of continuous and ordinal approaches
URL
http://www.ncbi.nlm.nih.gov/pubmed/23341367
Description
The role of the FOLFIRINOX regimen for advanced pancreatic cancer

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Quality of Life in Locally Advanced or Metastatic Pancreatic Cancer Treated With Gemcitabine and Nab-paclitaxel

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