Clinical trial NCT02812992: Geriatric Assessment Directed Trial to Evaluate Gemcitabine +/- Nab-paclitaxel in Elderly Pancreatic Cancer Patients
Official title: A Multicenter Phase 4 Geriatric Assessment Directed Trial to Evaluate Gemcitabine +/- Nab-paclitaxel in Elderly Pancreatic Cancer Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Adenocarcinoma Pancreas
Lead sponsor: AIO-Studien-gGmbH
Sponsor class: OTHER
First posted: 2016-06-24
Enrollment: 32
Sex: ALL
Minimum age (years): 70
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The GrantPax study is a multicenter phase 4 geriatric assessment directed trial to evaluate gemcitabine +/- nab-paclitaxel in elderly pancreatic cancer patients. 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).

Detailed description: 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).

Eligibility criteria: Inclusion Criteria 1 - Chemotherapy arms (Go-Go, Slow-Go):

1. Patients ≥ 70 years of age.
2. Histologically or cytologically confirmed metastatic adenocarcinoma of the pancreas.
3. At least one measurable lesion of disease according to RECIST 1.1 criteria.
4. No prior chemotherapy (except fluoruracil or gemcitabine in an adjuvant setting at least \> 6 months prior enrollment).
5. 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
6. Cooperation and willingness to complete all aspects of the study
7. Written informed consent to participate in the study

Inclusion criteria 2 - FRAIL arm:

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

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

1. Patients \<70 years of age.
2. Papillary cancer, cholangiocellular carcinoma, neuro-endocrine tumors.
3. Patient has a severe and/or uncontrolled medical disease (i.e. uncontrolled active infection, uncontrolled hypertension/ diabetes or cardiac disease).
4. Patient has received any other investigational product within 28 days prior study entry.
5. Patient is \< 5 years free of another primary malignancy (except: not currently clinically significant nor requiring active intervention)
6. Hypersensitivity against gemcitabine or nab-paclitaxel.
7. Major surgery ≤ 28 days prior to study entry.
8. Patient has a known diagnosis of human immunodeficiency virus (HIV) infection.
9. Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.
10. Any other chemotherapy at start.
11. Any psychiatric illness that would affect the patient's ability to understand the demands of the clinical trial.
12. 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.
13. Patient has already been recruited in this trial.
14. Patients who do not understand the nature, the scope and the consequences of the clinical trial.
15. Patient who might be dependent on the sponsor, the study site or the investigator.
16. 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:

1. Patients \<70 years of age.
2. Papillary cancer, cholangiocellular carcinoma, neuro-endocrine tumors.
3. Patient has received any other investigational product within 28 days prior study entry.
4. Patient is \< 5 years free of another primary malignancy (except: not currently clinically significant nor requiring active intervention)
5. Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.
6. Any chemotherapy at study start.
7. Any psychiatric illness that would affect the patient's ability to understand the demands of the clinical trial.
8. 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.
9. Patient has already been recruited in this trial.
10. Patients who do not understand the nature, the scope and the consequences of the clinical trial.
11. Patient who might be dependent on the sponsor, the study site or the investigator.
12. Patient who has been incarcerated or involuntarily institutionalized by court order or by the authorities § 40 Abs. 1 Nr. 4 AMG.

Primary outcomes:
measure: Barthel's ADL [Barthel's scale in activities of daily living]
timeFrame: 4 weeks
Secondary outcomes:
measure: CGA [Comprehensive Geriatric Assessment]
timeFrame: 4 weeks
measure: ECOG [Eastern Cooperative Oncology Group]
timeFrame: 4 weeks
measure: ADL (Barthel) [Activities of Daily Living]
timeFrame: 4 weeks
measure: IADL (Lawton/Browdy) [Instrumental Activities of Daily Living]
timeFrame: 4 weeks
measure: G8-Questionnaire
timeFrame: 4 weeks
measure: CR [Complete Response]
timeFrame: 12 months
measure: PR [Partial Response]
timeFrame: 12 months
measure: DCR [Disease Control Rate]
timeFrame: 12 months
measure: ORR [Objective Response Rate]
timeFrame: 12 months
measure: AEs/SAEs [Adverse Events/Serious Adverse Events]
timeFrame: 12 months
measure: PFS [Progression Free Survival]
timeFrame: 12 months
measure: OS [Overall Survival]
timeFrame: 12 months
measure: Percentage of patients receiving at least one chemotherapy in each treatment group
timeFrame: 12 months
measure: Percentage of patients escalating treatment
timeFrame: 12 months
measure: Duration of treatment
timeFrame: 12 months
measure: Cumulative dose
timeFrame: 12 months
measure: QoL [Quality of Life]
timeFrame: 12 months
measure: Discrepancy between CGA strata estimation by the investigator and true CGA assessment
timeFrame: 12 months
Other outcomes:
Locations:
city: Mannheim
country: Germany
facility: Universitätsklinikum Mannheim II. Medizinische Klinik
Study officials:
affiliation: Universitätsklinikum II. Medizinische Klinik
name: Matthias Ebert, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Betge J, Chi-Kern J, Schulte N, Belle S, Gutting T, Burgermeister E, Jesenofsky R, Maenz M, Wedding U, Ebert MP, Haertel N. A multicenter phase 4 geriatric assessment directed trial to evaluate gemcitabine +/- nab-paclitaxel in elderly pancreatic cancer patients (GrantPax). BMC Cancer. 2018 Jul 18;18(1):747. doi: 10.1186/s12885-018-4665-2.