A Randomized Phase II Study of Gemcitabine and Nab-Paclitaxel Compared with 5-Fluorouracil, Leucovorin, and Liposomal Irinotecan in Older Patients with Treatment Naïve Metastatic Pancreatic Cancer (GIANT)

By Efrat Dotan, MD

@efratdotan

Caring for older adults with cancer carries significant challenges and requires attention to multiple domains that affect older patients as they embark on anti-cancer therapy. This is further heightened by the significant underrepresentation of older adults in clinical trials.^{1, 2} Oncologists are frequently faced with these challenges when caring for older adults with metastatic pancreatic cancer, where age-related concerns compound those related to this aggressive cancer. The GIANT study (EA2186) aims to define an appropriate treatment approach for vulnerable older adults with newly diagnosed metastatic pancreatic cancer.³

GIANT is an elderly-specific clinical trial that will randomize 184 vulnerable older adults into one of two dose-attenuated treatment arms: Arm A, gemcitabine and nab-paclitaxel every two weeks; Arm B, 5-fluorouracil, leucovorin, and liposomal irinotecan (Onyvide^®) every two weeks. The primary objective of this phase 2 trial is overall survival with secondary efficacy endpoints of progressive-free survival and objective tumor response.

As this study focuses on the care of older patients, one main objective is to understand the toxicities experienced by this patient population during the treatment and evaluate any correlation between geriatric abnormalities, treatment-related toxicities, and outcomes. Therefore, the study utilizes geriatric assessments for thorough evaluation of our patient population. The study is enrolling patients over the age of 70 who are found to be vulnerable based on a short screening geriatric assessment. The assessment rates functional status, co-morbidities burden, and cognition using simple and quick assessment tools. Patients with mild to moderate abnormalities in any of these domains are considered vulnerable and eligible for the study. In addition, patients over the age of 80 are eligible for this trial if no severe geriatric abnormalities are identified in their screening assessment.

To further understand factors affecting treatment tolerance and outcomes, each enrolled patient completes a full baseline geriatric assessment evaluating additional domains, such as nutrition, psychosocial status, falls, and quality of life. With this comprehensive evaluation, we will understand the patient’s overall health and inform our analyses at the completion of the trial. Furthermore, throughout the trial, a short version of this assessment, focused on functional status and quality of life, is conducted at every disease evaluation, with the goal of understanding the effects of ongoing therapy on these factors. Researchers are also evaluating toxicities that are of interest for older patients (i.e., falls, ER visits, deterioration of performance status, etc.) and studying novel correlatives such as biomarkers of aging in the blood (IL6 and CRP) and the effect of sarcopenia on imaging and on outcomes.

To assist sites in mastering the use of the geriatric assessment, a manual was developed with step-by-step guidance for delivering and scoring each of these assessment tools. View the manual on the member section of the ECOG-ACRIN website (login required).

The ongoing GIANT trial (EA2186) is the first elderly-specific randomized clinical trial to focus on vulnerable older adults with treatment-naïve metastatic pancreatic cancer who are not candidates for standard therapy. In addition to providing much-needed guidance for the care of this vulnerable population, this trial will also lead the way in the conduct of elderly-specific clinical trials regardless of cancer type. For example, future studies may incorporate comprehensive geriatric assessments and thorough evaluations of outcomes like those developed for this trial. These features carry great significance for the older patient population. 

Learn more about the GIANT trial at ecog-acrin.org.

Dr. Dotan (Fox Chase Cancer Center) is the study chair for the GIANT trial (EA2186) and chair of the Geriatric Oncology Working Group, part of the ECOG-ACRIN Health Equity Committee.

The study co-chairs for this trial are Leon Lenchik, MD (Atrium Health Wake Forest Baptist), Robert D. Boutin, MD (Stanford Cancer Institute), and Xin Yao, MD (Consultant).

^{1Sedrak MS, et al. Older adult participation in cancer clinical trials: A systematic review of barriers and interventions. CA Cancer J Clin 2021; 71(1): p. 78-92.}

^{2White MN, et al. Advanced pancreatic cancer clinical trials: The continued underrepresentation of older patients. J Geriatr Oncol 2019; 10(4): p. 540-546.}

^{3 Dotan E, et al. The GIANT trial (ECOG-ACRIN EA2186) methods paper: A randomized phase II study of gemcitabine and nab-paclitaxel compared with 5-fluorouracil, leucovorin, and liposomal irinotecan in older patients with treatment-naive metastatic pancreatic cancer - defining a new treatment option for older vulnerable patients. J Geriatr Oncol 2023; 14(3): p. 101474.}