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, Study Chair

@efratdotan

The study co-chairs for this trial are Leon Lenchik, MD (Wake Forest University Health Sciences), Robert Boutin, MD (Stanford Cancer Institute), and Xin Yao, MD (ThedaCare Regional Cancer Center).

With the aging of the population in the US and around world, the number of older adults with cancer seen in clinical practice is expected to grow significantly. It is estimated that 67% of cancer incidence and the majority of cancer-related deaths occur in patients over the age of 65 ¹. Data regarding the management of older adults with cancer is lacking mainly due to the poor accrual of this age group on clinical trials ². This trend is also seen among patients with pancreatic cancer where the median age of diagnosis is 71 and the majority of cases are found in patients over the age of 65 ³.

Data is limited to guide therapy of older patients with metastatic pancreatic cancer (mPCA), with no available prospective studies and only a limited number of retrospective studies evaluating the optimal treatment approach in this patient population. The median age of patients enrolled on phase II and III pancreatic cancer clinical trials over the last two decades has been 62, limiting the applicability of these data for an older, less robust patient—the real-world patient we commonly encounter in daily practice ⁴. While some older adults present with multiple active geriatric syndromes, which preclude them from being candidates for aggressive chemotherapy, many older patients who are fit could derive benefit from combination chemotherapy, and are interested in receiving treatment ^{5 6}.

Given this gap in knowledge, the GIANT study (EA2186) was launched. The objective of this trial is to obtain much-needed data to guide oncologists as to the optimal management of vulnerable older patients over the age of 70 with newly diagnosed mPCA. The study design is novel in the use of a carefully designed screening geriatric assessment tool to identify older adults who are not candidates for standard therapy due to vulnerabilities, yet are candidates for an attenuated chemotherapy treatment. The quick screening assessment will rate functional status, co-morbidities burden, and cognition using simple tools. Patients with mild to moderate abnormalities in any of these assessments will be considered vulnerable and thus eligible for the study. In addition, patients over the age of 80 will be eligible for this trial as long as no severe geriatric abnormalities are identified in their screening assessment. Other eligibility criteria include ECOG performance status 0-2, no prior therapy for mPCA (adjuvant therapy must be completed 6 months before enrollment), adequate organ and marrow function, and evidence of measurable disease on scans.

Eligible patients will be randomized to one of two treatment arms using dose-reduced combination chemotherapy. On Arm A, patients will be treated with gemcitabine and nab-paclitaxel every two weeks. Alternatively, on Arm B, patients will receive dose-reduced 5-fluorouracil, leucovorin, and liposomal irinotecan (Onyvide®) every two weeks. All randomized patients will undergo a full geriatric assessment and quality of life evaluation prior to starting therapy on the study. During the trial, in addition to disease evaluation, we will monitor toxicity with specific attention to toxicities of interest for older adults (i.e., falls, performance status deterioration, admissions, and ER visits), effect of therapy on functional status, and quality of life.

The primary endpoint of the study is overall survival, with secondary endpoints of progressive-free survival, objective tumor response, and the correlation between geriatric factors and outcomes. The study also includes imaging correlatives evaluating the effect of sarcopenia on treatment outcome, as well as laboratory correlatives evaluating the correlation between biomarkers of aging (CRP and IL6) and outcomes. The study is open for enrollment and the goal is to accrue a total of 184 patients (92 patients per treatment arm).

The GIANT trial (EA2186) is the first randomized clinical trial to focus on vulnerable older adults with treatment-naïve metastatic pancreatic cancer who are not candidates for standard therapy. Data from this trial will define the appropriate treatment regimen for this vulnerable patient population and help us better understand the factors that affect care and outcomes in this prevalent group of patients.

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

References:

^{1. Siegel, R.L., et al., Cancer Statistics, 2021. CA Cancer J Clin, 2021. 71(1): p. 7-33.↩}

^{2. Sedrak, M.S., 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.↩}

^{3. SEER Cancer Stat Facts: Pancreatic Cancer. National Cancer Institute. Bethesda, MD,. https://seer.cancer.gov/statfacts/html/pancreas.html.↩}

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

^{5. Vijayvergia, N., et al., Patterns of care and outcomes of older versus younger patients with metastatic pancreatic cancer: A Fox Chase Cancer Center experience. J Geriatr Oncol, 2015. 6(6): p. 454-61.↩}

^{6. Aldoss, I.T., et al., Role of chemotherapy in the very elderly patients with metastatic pancreatic cancer — A Veterans Affairs Cancer Registry analysis. Journal of Geriatric Oncology, 2011. 2(3): p. 209-214.↩}