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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: Nab-paclitaxel
* Drug: Gemcitabine


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>Nab-paclitaxel - IV - 125 mg/m2 - 3xq4wks Gemcitabine - IV - 1000 mg/m2 - 3xq4wks | Drug: Nab-paclitaxel<br> <br> * Other names: Abraxane, EU/1/07/428/001, L01CD01;Drug: Gemcitabine<br> <br> * Other names: Gemzar;|
| Active Comparator: Arm B<br>Gemcitabine - IV - 1000 mg/m2 - 3xq4wks | Drug: Gemcitabine<br> <br> * Other names: Gemzar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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) | 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. | 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 | 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. | 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 | 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). | 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 | Overall survival was considered from start of treatment to death. All patients (ITT) | 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). | 
| Laboratory Safety Assessment | Severe laboratory abnormalities (hematology and biochemistry grade 3 and higher). Worst grade per patient. All patients treated (Safety set). | 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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pancreatic cancer, Locally advanced, Metastatic