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

A Multicenter Phase 4 Geriatric Assessment Directed Trial to Evaluate Gemcitabine +/- Nab-paclitaxel in Elderly Pancreatic Cancer Patients

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).

Study Overview

• Status: Completed
• Conditions: Adenocarcinoma Pancreas
• Intervention / Treatment: Drug: Gemcitabine; Other: Best Supportive Care; Drug: Nab-paclitaxel

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).

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • Mannheim, Germany, 68167
    • Universitätsklinikum Mannheim II. Medizinische Klinik

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 70 years and older (OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: GO-GO arm; Nab-paclitaxel 125 mg/m^2 i.v. over 30 minutes followed by gemcitabine infusion 1000 mg/m^2 on days D1, D8, D15 of a 28-day cycle.	Drug: Gemcitabine; Drug: Nab-paclitaxel; Other Names: Abraxane®
ACTIVE_COMPARATOR: SLOW-GO arm; Gemcitabine 1000 mg/m^2 i.v. on days D1, D8, D15 of a 28-day cycle.	Drug: Gemcitabine
ACTIVE_COMPARATOR: FRAIL arm; Best supportive care as determined by the investigator.	Other: Best Supportive Care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Barthel's ADL [Barthel's scale in activities of daily living]	Loss of five points or less in the Activity of Daily Living (Barthel's ADL; assessed during 2nd CGA) after first cycle of chemotherapy (or after 4 weeks in BSC group) compared to the initial ADL for each treatment groups.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CGA [Comprehensive Geriatric Assessment]	Scores before and after 1st treatment cycle (CGA1+2 further CGA scores 3+4 - if available) or after 28 days of BSC	4 weeks
ECOG [Eastern Cooperative Oncology Group]	Scores before and after 1st treatment cycle (CGA1+2 further CGA scores 3+4 - if available) or after 28 days of BSC	4 weeks
ADL (Barthel) [Activities of Daily Living]	Scores before and after 1st treatment cycle (CGA1+2 further CGA scores 3+4 - if available) or after 28 days of BSC	4 weeks
IADL (Lawton/Browdy) [Instrumental Activities of Daily Living]	Scores before and after 1st treatment cycle (CGA1+2 further CGA scores 3+4 - if available) or after 28 days of BSC	4 weeks
G8-Questionnaire	Scores before and after 1st treatment cycle (CGA1+2 further CGA scores 3+4 - if available) or after 28 days of BSC	4 weeks
CR [Complete Response]		12 months
PR [Partial Response]		12 months
DCR [Disease Control Rate]		12 months
ORR [Objective Response Rate]		12 months
AEs/SAEs [Adverse Events/Serious Adverse Events]		12 months
PFS [Progression Free Survival]		12 months
OS [Overall Survival]		12 months
Percentage of patients receiving at least one chemotherapy in each treatment group		12 months
Percentage of patients escalating treatment		12 months
Duration of treatment		12 months
Cumulative dose		12 months
QoL [Quality of Life]	time to QoL deterioration [loss of 10 points or more in QLQ-C30]	12 months
Discrepancy between CGA strata estimation by the investigator and true CGA assessment		12 months

Collaborators and Investigators

• Sponsor: AIO-Studien-gGmbH
• Investigators: Principal Investigator: Matthias Ebert, Prof., Universitätsklinikum II. Medizinische Klinik

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 1, 2016
• Primary Completion (ACTUAL): February 1, 2020
• Study Completion (ACTUAL): February 1, 2021

Study Registration Dates

• First Submitted: June 7, 2016
• First Submitted That Met QC Criteria: June 23, 2016
• First Posted (ESTIMATE): June 24, 2016

Study Record Updates

• Last Update Posted (ACTUAL): August 10, 2021
• Last Update Submitted That Met QC Criteria: August 3, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Gemcitabine; Paclitaxel
• Other Study ID Numbers: AIO-GER-0115

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO