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JCOG1611: Randomized phase II/III study of gemcitabine plus nab-paclitaxel combination therapy versus modified FOLFIRINOX versus S-IROX for metastatic or recurrent pancreatic cancer (GENERATE)

JCOG1611: Randomized phase II/III study of gemcitabine plus nab-paclitaxel combination therapy versus modified FOLFIRINOX versus S-IROX for metastatic or recurrent pancreatic cancer (GENERATE)

527

Please find the "JCOG1611 clinical study report" file in the "Attached files: statistical analysis plan" section below. You will also find the "statistical analysis plan" file in the same section.

Please find the "JCOG1611 clinical study report" file in the "Attached files: statistical analysis plan" section below. You will also find the "statistical analysis plan" file in the same section.

Please find the "JCOG1611 clinical study report" file in the "Attached files: statistical analysis plan" section below. You will also find the "statistical analysis plan" file in the same section.

The primary endpoint for the efficacy of this study was overall survival, and one interim analysis was planned during the study period. At the time of the interim analysis, a total of 527 patients were enrolled and 426 patients were included in the interim analysis. The median overall survival was 14.0 months (HR 1.31, 95% CI 0.97-1.77) and 13.6 months (HR 1.35, 95% CI 1.00-1.82) in the mFOLFIRINOX and S-IROX arms, respectively, as compared with 17.1 months in the nab-paclitaxel + gemcitabine arm. The predictive probability of achieving superiority in the final analysis was 0.73% and 0.48% in the mFOLFIRINOX and S-IROX arms, respectively. Thus, this study was terminated owing to its futility. The median OS was 15.3 months in the GnP arm, 12.5 months in the mFOLFIRINOX arm (HR 1.27, 95% CI 1.01-1.61), and 13.2 months in the S-IROX arm (HR 1.23, 95% CI 0.98-1.56).

Compared to mFOLFIRINOX or S-IROX, nab-paclitaxel + gemcitabine is recommended as the first-line treatment for metastatic or recurrent pancreatic cancer.

April. 10, 2025

No

-

https://jrct.mhlw.go.jp/latest-detail/jRCTs031190009

UENO Makoto

Kanagawa Cancer Center

2-3-2, Nakao, Asahi-ku, Yokohama City, Kanagawa

Kantansui-renkei@kcch.jp

KOBAYASHI Satoshi

Kanagawa Cancer Center

2-3-2, Nakao, Asahi-ku, Yokohama City, Kanagawa

+81-45-520-2222

Kantansui-renkei@kcch.jp

Complete

April. 15, 2019

Interventional

randomized controlled trial

open(masking not used)

active control

parallel assignment

treatment purpose

(1) Histologically or cytologically proven pancreatic carcinoma meeting either one of the following conditions in primary tumor or metastatic lesion.
(i) Histologically proven invasive ductal carcinoma; adenocarcinoma (well differentiated type, moderately differentiated type, or poorly differentiated adenocarcinoma) or adenosquamous carcinoma, and it is radiologically diagnosed to be compatible with invasive ductal carcinoma
(ii) Cytologically proven Class IV or Class V and it is radiologically diagnosed to be compatible with invasive ductal carcinoma
(2) The presence of organ metastasis or recurrent pancreatic cancer by chest computed tomography (CT) and enhanced abdominal/pelvic CT or magnetic resonance imaging (MRI).
(3) The absence of massive ascites by enhanced abdominal/pelvic CT or MRI.
(4) No evidence of central nervous system metastases with symptoms. Brain CT and/or MRI before registration is not required.
(5) Age, 20 - 75 years.
(6) ECOG performance status, 0 or 1.
(7) Phase II: A measurable lesion is required by chest and enhanced abdominal/pelvic CT or MRI. Phase III: A measurable lesion is not required.
(8) No previous chemotherapy or radiotherapy for pancreatic cancer. Patients with recurrent cancer 24 or more weeks after receiving postoperative chemotherapy of S-1 or gemcitabine is eligble. Patients with recurrent cancer 24 or more weeks after receiving preoperative chemotherapy of gemcitabine plus S-1 and postoperative chemotherapy of S-1 or gemcitabine is eligble.
(9) No watery stool.
(10) No grade 2 or greater peripheral sensory neuropathy or peripheral motor neuropathy.
(11) Sufficient oral intake
(12) UGT1A1 genotypes that do not include *6/*6, *28/*28, or *6/*28.
(13) Adequate function of major organs.
(14) Written informed consent.

(1) Synchronous or metachronous (within 2 years) malignancies.
(2) Infectious disease requiring systemic treatment (excluding hepatitis viral).
(3) Pyrexia of 38 or higher degrees centigrade.
(4) Female during pregnancy, within 28 days of postparturition, or during lactation and male expecting partner's pregnancy.
(5) Severe psychological disorders.
(6) Receiving continuous systemic corticosteroid or immunosuppressants.
(7) Interstitial pneumonia, pulmonary fibrosis, or severe emphysema on chest CT.
(8) Severe comorbidities (such as heart failure, renal failure, hepatic failure, paresis of intestine, ileus, poorly controlled diabetes, or poorly controlled hypertension).
(9) History of unstable angina pectoris with new onset or exacerbation within recent 3 weeks or myocardial infarction within 6 months before registration.
(10) Requiring continuous administration of either one of flucytosine, phenytoin, or warfarin.
(11) Allergy to iodine or gadolinium.

Both

metastatic or recurrent pancreatic cancer

Arm A: GnP therapy. Repeated every four weeks until meeting stopping criteria. nab-paclitaxel 125 mg/m2 day 1, 8, 15, gemcitabine 1,000 mg/m2 day 1, 8, 15.

Arm B: mFOLFIRINOX therapy. Repeated every two weeks until meeting stopping criteria. oxaliplatin 85 mg/m2 day 1, leucovorin 200 mg/m2 day 1, irinotecan 150 mg/m2 day 1, fluorouracil 2,400 mg/m2 day 1-3 (46 hours)

Arm C: S-IROX therapy. Repeated every two weeks until meeting stopping criteria. oxaliplatin 85 mg/m2 day 1, irinotecan 150 mg/m2 day 1, S-1 80-120 mg/day day 1-7

Phase II part: objective response rate in Arm C
Phase III part: overall survival

Phase II part: adverse events and serious adverse events in Arm C
Phase III part: progression-free survival, objective response rate, adverse events, serious adverse events, dose intensity

+81-3-3542-2511

Feb. 28, 2019

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