Safety and Efficacy Study of mFOLFOX6 + Panitumumab Combination Therapy and 5-FU/LV + Panitumumab Combination Therapy in Participants With Chemotherapy-naïve Unresectable Advanced Recurrent Colorectal Carcinoma
SAPPHIRE
A Phase 2 Randomized Study Comparing the Efficacy and Safety of mFOLFOX6+Panitumumab Combination Therapy and 5-FU/LV+Panitumumab Combination Therapy in the Patients With Chemotherapy-Naive Unresectable Advanced Recurrent Colorectal Carcinoma of KRAS Wild-Type After 6 Cycles of Combination Therapy With mFOLFOX6+Panitumumab
4 other identifiers
interventional
164
1 country
49
Brief Summary
The purpose of this study is to exploratorily examine efficacy and safety in the participants with chemotherapy-naïve unresectable, advanced/recurrent colorectal carcinoma of Kirsten rat sarcoma-2 virus (KRAS) wild-type who have been treated with 6 cycles (2 weeks/cycle) of first-line mFOLFOX6 + panitumumab combination therapy and then assigned to two groups i.e., a group receiving 5-FU/LV + panitumumab combination therapy and a group receiving mFOLFOX6 + panitumumab combination therapy.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Oct 2014
Typical duration for phase_2
49 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 30, 2014
CompletedStudy Start
First participant enrolled
October 16, 2014
CompletedFirst Posted
Study publicly available on registry
January 14, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 31, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
August 31, 2017
CompletedResults Posted
Study results publicly available
March 1, 2019
CompletedSeptember 10, 2019
August 1, 2019
2.5 years
September 30, 2014
March 27, 2018
August 28, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression-Free Survival Rate (PFS Rate) at 9 Months After Randomization
PFS rate was defined as the gross percentage of participants who survived with no evidence of progression from the day of randomization (Day 0) until 9 months after Day 0. The presence/absence of progressive disease (PD) was determined based on imaging, consideration of clinical PD, or survival research results. PD based on response evaluation criteria in solid tumors (RECIST) is at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Up to 9 months after randomization
Secondary Outcomes (8)
Progression-Free Survival (PFS)
Up to approximately 31 months
Overall Survival (OS)
Up to approximately 31 months
Response Rate (RR)
Up to approximately 31 months
Time to Treatment Failure (TTF)
Up to approximately 31 months
Percentage of Participants With Adverse Events
Up to 28 days after discontinuation of study drug or start of subsequent therapy (data cut off: 31 August 2017; Overall study completion date)
- +3 more secondary outcomes
Study Arms (2)
Group A
ACTIVE COMPARATORPanitumumab (Pmab) 6 mg/kg, intravenous drip infusion (DIV), at Day 1, oxaliplatin (OXA) 85 mg/m\^2, DIV, at Day 1, levofolinate (l LV) 200 mg/m\^2, DIV, at Day 1, fluorouracil (5-FU) 400 mg/m\^2, intravenous (IV) at Day 1, 5-FU 2400 mg/m\^2, continuous intravenous infusion (CIV), at Day 2 once every two weeks from cycle 1 through cycle 6 as protocol treatment 1 followed by Pmab 6 mg/kg, DIV, at Day 1, OXA 85 mg/m\^2, DIV, at Day 1, l LV 200 mg/m\^2, DIV, at Day 1, 5-FU 400 mg/m\^2, IV, at Day 1, 5-FU 2400 mg/m\^2, CIV, at Day 2 once every two weeks from cycle 7 until progressive disease or intolerance.
Group B
EXPERIMENTALPmab 6 mg/kg, DIV, at Day 1, OXA 85 mg/m\^2, DIV, at Day 1, l LV 200 mg/m\^2, DIV, at Day 1, 5-FU 400 mg/m\^2, IV, at Day 1, 5-FU 2400 mg/m\^2, CIV, at Day 2 once every two weeks from cycle 1 through cycle 6 as protocol treatment 1 followed by Pmab 6 mg/kg, DIV, at Day 1, l LV 200 mg/m\^2, DIV, at Day 1, 5-FU 400 mg/m\^2, IV, at Day 1, 5-FU 2400 mg/m\^2, CIV, at Day 2 once every two weeks from cycle 7 until progressive disease or intolerance.
Interventions
oxaliplatin (OXA), levofolinate calcium (l-LV), panitumumab: intra-venous infusion 5-FU: bolus and continuous intra-venous infusion
Eligibility Criteria
You may qualify if:
- Participants with unresectable adenocarcinoma originating in the large intestine (excluding carcinoma of the appendix and anal canal cancer)
- Participants with measurable lesion(s) according to the RECIST ver. 1.1
- Participants who have not received chemotherapy for colorectal cancer. Participants who experience relapse more than 6 months after the final dose of perioperative adjuvant chemotherapy with fluoropyrimidine agents may be enrolled.
- Aged ≥ 20 years at the time of enrollment
- Participants classified as KRAS wild-type. However, the criteria will be changed to all patients who are verified to be of KRAS and NRAS wild-type when the KRAS and NRAS tests come to be covered by National Health Insurance, and the tests become feasible at medical institutions.
- Participants who satisfy the following criteria for the major organ function in tests performed within 14 days prior to enrollment
- Neutrophil count ≥ 1.5 × 10\^3/μL
- White blood cell count ≥ 3.0 × 10\^3/μL
- Platelet count ≥ 10.0 × 10\^4/μL
- Hemoglobin ≥ 9.0 g/dL
- Total bilirubin ≤ 2.0 mg/dL
- AST ≤ 100 U/L (≤ 200 U/L if liver metastases are present)
- ALT ≤ 100 U/L (≤ 200 U/L if liver metastases are present)
- Serum creatinine ≤ 1.5 mg/dL
- Participants who are assessed at Eastern Cooperative Oncology Group (ECOG) performance status (P.S.) of 0 or 1
- +5 more criteria
You may not qualify if:
- Radiotherapy received for a measurable lesion
- Radiotherapy received within 28 days (4 weeks) prior to enrollment for a lesion other than measurable lesions. However, treatment to relieve pain associated with metastatic bone tumors was allowed.
- Known brain metastasis or strongly suspected of brain metastasis
- Synchronous cancers or metachronous cancers with a disease-free period of ≤ 5 years (excluding colorectal cancer) excluding mucosal cancers cured or be possibly cured by regional resection (esophageal, stomach, and cervical cancer, non-melanoma skin cancer, bladder cancer, etc.).
- Body cavity fluid that requires treatment (pleural effusion, ascites, pericardial effusion, etc.)
- Participants who do not want to use contraception to prevent pregnancy, and women who are pregnant or breast-feeding, or test positive for pregnancy
- Active hemorrhage requiring blood transfusion
- Disease requiring systemic steroids for treatment (excluding topical steroids)
- Intestinal resection and colostomy within 2 weeks prior to enrollment
- History or obvious and extensive CT findings of interstitial pulmonary disease (interstitial pneumonia, pulmonary fibrosis, etc.)
- Serious drug hypersensitivity
- Local or systemic active infection requiring treatment, or fever indicating infection
- Intestinal paralysis, gastrointestinal obstruction, or uncontrollable diarrhea (incapacitating symptoms despite adequate treatment)
- Active hepatitis B and/or active hepatitis C
- Known human immunodeficiency virus infection
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Takedalead
Study Sites (49)
Unknown Facility
Nagakute, Aichi-ken, Japan
Unknown Facility
Nagoya, Aichi-ken, Japan
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Okazaki, Aichi-ken, Japan
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Toyoaki, Aichi-ken, Japan
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Yachiyo, Chiba, Japan
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Kitakyushu, Fukuoka, Japan
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Tagawa, Fukuoka, Japan
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Aizu-Wakamatsu, Fukushima, Japan
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Kakamigahara, Gifu, Japan
Unknown Facility
Tajimi, Gifu, Japan
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Hakodate, Hokkaido, Japan
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Kushiro, Hokkaido, Japan
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Amagasaki, Hyōgo, Japan
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Kakogawa, Hyōgo, Japan
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Kobe, Hyōgo, Japan
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Nishinomiya, Hyōgo, Japan
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Kahoku, Ishikawa-ken, Japan
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Kanazawa, Ishikawa-ken, Japan
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Morioka, Iwate, Japan
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Kida-gun, Kagawa-ken, Japan
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Marugame, Kagawa-ken, Japan
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Takamatsu, Kagawa-ken, Japan
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Kawasaki, Kanagawa, Japan
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Yokohama, Kanagawa, Japan
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Nangoku, Kochi, Japan
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Sendai, Miyagi, Japan
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Matsumoto, Nagano, Japan
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Suwa, Nagano, Japan
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Sasebo, Nagasaki, Japan
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Higashiosaka, Osaka, Japan
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Hirakata, Osaka, Japan
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Izumi, Osaka, Japan
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Izumisano, Osaka, Japan
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Sakai, Osaka, Japan
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Tondabayashi, Osaka, Japan
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Hidaka, Saitama, Japan
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Izumo, Shimane, Japan
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Fujioka, Shizuoka, Japan
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Shimonoseki, Yamaguchi, Japan
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Akita, Japan
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Fukui, Japan
Unknown Facility
Fukuoka, Japan
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Gifu, Japan
Unknown Facility
Hiroshima, Japan
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Kyoto, Japan
Unknown Facility
Nagasaki, Japan
Unknown Facility
Okinawa, Japan
Unknown Facility
Osaka, Japan
Unknown Facility
Saga, Japan
Related Publications (2)
Munemoto Y, Nakamura M, Takahashi M, Kotaka M, Kuroda H, Kato T, Minagawa N, Noura S, Fukunaga M, Kuramochi H, Touyama T, Takahashi T, Miwa K, Satake H, Kurosawa S, Miura T, Mishima H, Sakamoto J, Oba K, Nagata N. SAPPHIRE: a randomised phase II study of planned discontinuation or continuous treatment of oxaliplatin after six cycles of modified FOLFOX6 plus panitumumab in patients with colorectal cancer. Eur J Cancer. 2019 Sep;119:158-167. doi: 10.1016/j.ejca.2019.07.006. Epub 2019 Aug 21.
PMID: 31445198BACKGROUNDNagata N, Mishima H, Kurosawa S, Oba K, Sakamoto J. 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. Clin Colorectal Cancer. 2017 Jun;16(2):154-157.e1. doi: 10.1016/j.clcc.2017.02.001. Epub 2017 Mar 1.
PMID: 28284575DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Director
- Organization
- Takeda
Study Officials
- STUDY DIRECTOR
Study Director
Takeda
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 30, 2014
First Posted
January 14, 2015
Study Start
October 16, 2014
Primary Completion
March 31, 2017
Study Completion
August 31, 2017
Last Updated
September 10, 2019
Results First Posted
March 1, 2019
Record last verified: 2019-08
Data Sharing
- IPD Sharing
- Will share
Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.