Geriatric Assessment Directed Trial to Evaluate Gemcitabine +/- Nab-paclitaxel in Elderly Pancreatic Cancer Patients

The hypothesis of the proposed study is that individualized assessment directed treatment algorithms identifies elderly patients, who benefit from combined nab-paclitaxel/gemcitabine therapy. The project uses a CGA, which includes various tests and scoring systems, to stratify patients as "GO-GO", "SLOW-GO" or "FRAIL" patients. Depending on test results patients receive chemotherapy (GO-GO group: nab-paclitaxel/gemcitabine; SLOW-GO group: gemcitabine monotherapy) or best supportive care (FRAIL group). After the first cycle of chemotherapy (4 weeks) a subsequent CGA and a safety assessment will be performed to assign patients to their definite treatment arm. The primary objective is that CGA-stratified patients do not decline in their CGA performance in response to chemotherapy measured as a loss of five points or less in the Barthel's ADL (ADL1 vs. ADL2 during core CGA assessment).

Inclusion criteria

1 - Chemotherapy arms (Go-Go, Slow-Go):

• Patients ≥ 70 years of age.
• Histologically or cytologically confirmed metastatic adenocarcinoma of the pancreas.
• At least one measurable lesion of disease according to RECIST 1.1 criteria.
• No prior chemotherapy (except fluoruracil or gemcitabine in an adjuvant setting at least > 6 months prior enrollment).
• Adequate end organ function:

• renal function: serum creatinine ≤ 1.5 x ULN or GFR ≥ 30mL/min.
• hematopoietic function: white blood cell (WBC) count ≥3000/μL, absolute neutrophil count (ANC) ≥ 1500/μL, platelets ≥10^5/μL, hemoglobin level >9.0 g/dL
• liver function: total bilirubin ≤1.5 x ULN, AST / ALT ≤3.0 x ULN
• Cooperation and willingness to complete all aspects of the study
• Written informed consent to participate in the study

Inclusion criteria

2 - FRAIL arm:

• Patients ≥ 70 years of age.
• Histologically or cytologically confirmed metastatic adenocarcinoma of the pancreas.
• No prior chemotherapy (except fluoruracil or gemcitabine in an adjuvant setting at least > 6 months prior enrollment).
• Cooperation and willingness to complete all aspects of the study
• Written informed consent to participate in the study

Exclusion criteria

1 - Chemotherapy arms (Go-Go, Slow-Go):

• Patients <70 years of age.
• Papillary cancer, cholangiocellular carcinoma, neuro-endocrine tumors.
• Patient has a severe and/or uncontrolled medical disease (i.e. uncontrolled active infection, uncontrolled hypertension/ diabetes or cardiac disease).
• Patient has received any other investigational product within 28 days prior study entry.
• Patient is < 5 years free of another primary malignancy (except: not currently clinically significant nor requiring active intervention)
• Hypersensitivity against gemcitabine or nab-paclitaxel.
• Major surgery ≤ 28 days prior to study entry.
• Patient has a known diagnosis of human immunodeficiency virus (HIV) infection.
• Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.
• Any other chemotherapy at start.
• Any psychiatric illness that would affect the patient's ability to understand the demands of the clinical trial.
• Parallel participation in another clinical trial or participation in another clinical trial within the last 30 days or 7 half-lifes of a study medication, whichever is of longer duration, prior study start.
• Patient has already been recruited in this trial.
• Patients who do not understand the nature, the scope and the consequences of the clinical trial.
• Patient who might be dependent on the sponsor, the study site or the investigator.
• Patient who has been incarcerated or involuntarily institutionalized by court order or by the authorities § 40 Abs. 1 Nr. 4 AMG.

Exclusion criteria

2 - FRAIL arm:

• Patients <70 years of age.
• Papillary cancer, cholangiocellular carcinoma, neuro-endocrine tumors.
• Patient has received any other investigational product within 28 days prior study entry.
• Patient is < 5 years free of another primary malignancy (except: not currently clinically significant nor requiring active intervention)
• Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.
• Any chemotherapy at study start.
• Any psychiatric illness that would affect the patient's ability to understand the demands of the clinical trial.
• Parallel participation in another clinical trial or participation in another clinical trial within the last 30 days or 7 half-lifes of a study medication, whichever is of longer duration, prior study start.
• Patient has already been recruited in this trial.
• Patients who do not understand the nature, the scope and the consequences of the clinical trial.
• Patient who might be dependent on the sponsor, the study site or the investigator.
• Patient who has been incarcerated or involuntarily institutionalized by court order or by the authorities § 40 Abs. 1 Nr. 4 AMG.