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

NCT02106884 | Completed Phase 2 Results

• 3 other identifiers: s561222013-004101-75AX-CL-PANC-PI-003568
• Study Type: interventional
• Target: 146
• Locations: 1 country
• Sites: 18

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.

Conditions

Pancreatic Cancer

Keywords

Pancreatic cancer; Locally advanced; Metastatic

Outcome Measures

Primary Outcomes (2)

• 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.

  From date of randomisation to 3, 6 and 12 months respectively

• 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.

  From date of randomisation to end of follow up (max 3 years after database lock when applicable).

Secondary Outcomes (6)

• Overall Response

  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).

• Duration of Response (in Responders)

  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).

• Disease Control

  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).

• Progression Free Survival

  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).

• Overall Survival

  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).

Study Arms (2)

Arm A

EXPERIMENTAL

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

Drug: Nab-paclitaxel; Drug: Gemcitabine

Arm B

ACTIVE COMPARATOR

Gemcitabine - IV - 1000 mg/m2 - 3xq4wks

Drug: Gemcitabine

Interventions

Nab-paclitaxel DRUG

Also known as: Abraxane, EU/1/07/428/001, L01CD01

Arm A

Gemcitabine DRUG

Also known as: Gemzar

Arm A; Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven: lead
• Celgene Corporation: collaborator

Study Sites (18)

OLV Ziekenhuis Aalst

Aalst, 9300, Belgium

Location

AZ Klina

Brasschaat, 2930, Belgium

Location

AZ St Lucas

Bruges, 8310, Belgium

Location

ULB Hôpital Erasme

Brussels, 1070, Belgium

Location

Cliniques Universitaires St Luc

Brussels, 1200, Belgium

Location

CHU de Charleroi

Charleroi, 6110, Belgium

Location

UZ Antwerpen

Edegem, 2650, Belgium

Location

AZ Maria Middelares

Ghent, 9000, Belgium

Location

UZ Gent

Ghent, 9000, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

Heilig Hartziekenhuis Lier

Lier, 2500, Belgium

Location

CHC St Joseph

Liège, 4000, Belgium

Location

CHR Citadelle

Liège, 4000, Belgium

Location

CHU Sart-Tilman

Liège, 4000, Belgium

Location

AZ Sint Maarten

Mechelen, 2800, Belgium

Location

Clinique St Elisabeth

Namur, 5000, Belgium

Location

AZ Delta

Roeselare, Belgium

Location

AZ Turnhout

Turnhout, 2300, Belgium

Location

Related Links

• The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology.
• 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.
• Time until definitive quality of life score deterioration as a means of longitudinal analysis for treatment trials in patients with metastatic pancreatic adenocarcinoma.
• Pancreatic cancer: optimizing treatment options, new, and emerging targeted therapies.
• Quality, interpretation and presentation of European Organisation for Research and Treatment of Cancer quality of life questionnaire core 30 data in randomised controlled trials
• FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer
• nab-Paclitaxel plus gemcitabine for metastatic pancreatic cancer: long-term survival from a phase III trial.
• 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.
• 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.
• Quality of life data as prognostic indicators of survival in cancer patients: an overview of the literature from 1982 to 2008.
• 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.
• Baseline quality of life as a prognostic indicator of survival: a meta-analysis of individual patient data from EORTC clinical trials.
• A global analysis of multitrial data investigating quality of life and symptoms as prognostic factors for survival in different tumor sites.
• Pancreatic adenocarcinoma.
• Metastatic Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline
• Metastatic Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline Summary.Metastatic Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline Summary.
• Gemcitabine plus nab-paclitaxel is an active regimen in patients with advanced pancreatic cancer: a phase I/II trial.
• Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine.
• Metastatic Pancreatic Cancer: ASCO Clinical Practice Guideline Update.
• Joint modeling of longitudinal health-related quality of life data and survival
• Longitudinal quality of life data: a comparison of continuous and ordinal approaches
• The role of the FOLFIRINOX regimen for advanced pancreatic cancer

MeSH Terms

Conditions

Pancreatic Neoplasms; Neoplasm Metastasis

Interventions

130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel; Gemcitabine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Limitations and Caveats

Quality of life endpoints are sensitive to confounding factors such as age, intercurrent disease, time from last completed questionnaire to the last follow-up or death. Tumour response and AE relationship to treatment were locally adressed.

Results Point of Contact

• Title: Prof. Dr. Eric Van Cutsem
• Organization: UZ Leuven

eric.vancutsem@uzleuven.be

0032 16 344418

Study Officials

• Eric Van Cutsem, MD

  UZ Leuven

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 21, 2014
• First Posted: April 8, 2014
• Study Start: April 1, 2014
• Primary Completion: April 29, 2019
• Study Completion: April 29, 2019
• Last Updated: November 6, 2019
• Results First Posted: October 24, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

BE (18)