title: mFOLFOX6 Plus Panitumumab Versus 5-FU/LV Plus Panitumumab After Six Cycles of Frontline mFOLFOX6 Plus Panitumumab: A Randomized Phase II Study of Patients With Unresectable or Advanced/Recurrent, RAS Wild-type Colorectal Carcinoma (SAPPHIRE)-Study Design and Rationale.
abstract: In Japan, oxaliplatin (OXA)/5-fluorouracil (5-FU)/leucovorin (LV)-the mFOLFOX6 regimen-is the most frequently used first-line chemotherapy backbone for metastatic colorectal cancer. However, peripheral nerve disorders caused by OXA during mFOLFOX6 therapy can decrease patients' quality of life. OXA can be safely discontinued from a FOLFOX regimen after 6 cycles during first-line therapy. Also, for patients who discontinue OXA without having experienced peripheral nerve disorders, reintroducing OXA in the later stages of treatment could remain an option.
  
  
  
  The study is a phase II, multicenter, open-label, parallel-group, randomized, controlled exploratory study comparing the efficacy and safety of mFOLFOX6 plus panitumumab and 5-FU/LV plus panitumumab in patients with chemotherapy-naïve, unresectable, advanced or recurrent colorectal carcinoma of RAS wild-type (SAPPHIRE; ClinicalTrials.gov identifier, NCT02337946). Eligible patients will receive 6 cycles of mFOLFOX6 plus panitumumab combination therapy, followed by 1:1 randomization to either further treatment with mFOLFOX6 plus panitumumab or discontinuation of OXA and treatment with 5-FU/LV plus panitumumab. Up to 100 randomized patients will receive treatment for approximately 12 months or until any of the criteria for treatment discontinuation have been met. The primary endpoint is progression-free survival rate at 9 months after the day of randomization. The secondary endpoints are progression-free survival, overall survival, response rate, and interval to treatment failure. Safety will be evaluated according to the incidence and severity of adverse events, including the incidence of peripheral nerve and skin disorders. Additional endpoints will include maintenance of performance status, continuation of OXA in the mFOLFOX6 plus panitumumab group, and continuation of panitumumab in both groups.
authors.affiliation: Kitakyushu General Hospital, Kitakyushu, Japan. Electronic address: n-nagata@kitakyu-hp.or.jp.
authors.forename: Naoki
authors.initials: N
authors.lastname: Nagata
authors.affiliation: Aichi Medical University, Nagakute, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Mishima
authors.affiliation: Takeda Pharmaceutical Company Limited, Tokyo, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kurosawa
authors.affiliation: The University of Tokyo, Tokyo, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Oba
authors.affiliation: Tokai Central Hospital, Kakamigahara, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Sakamoto
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077544:Panitumumab; D011788:Quality of Life; D012107:Research Design; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D009944:Organoplatinum Compounds; D000077544:Panitumumab; D002955:Leucovorin; D005472:Fluorouracil
keywords: Anti-EGFR; Clinical trial; Maintenance; Non comparative; Oxaliplatin