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

JRCT ID: jRCTs031190009

Registered date:15/04/2019

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: metastatic or recurrent pancreatic cancer
• Date of first enrollment: 08/05/2019
• Target sample size: 732
• Study type: Interventional

Intervention(s)

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

Outcome(s)

Primary Outcome

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

Secondary Outcome

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

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: <= 75age old
• Gender: Both

Include criteria

(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.

Exclude criteria

(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.

Related Information

• Primary Sponsor: UENO Makoto
• Source(s) of Monetary Support: National Cancer Center Japan,Japan Agency for Medical Research and Development