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| ID | Type | Description | Link |
|---|---|---|---|
| U1111-1161-8871 | Registry Identifier | UTN (WHO) | |
| 183/NRP-005 | Other Identifier | Secondary Takeda ID | |
| JapicCTI-142668 | Registry Identifier | JapicCTI |
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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.
The drug being tested in this study is called panitumumab. Panitumumab is being tested to treat people who have advanced/recurrent colorectal carcinoma of KRAS wild-type. This study will look at the efficacy and safety of 5-FU/LV + panitumumab(Pmab) combination therapy or mFOLFOX6 + Pmab combination therapy in the participants.
The study will enroll 164 patients. All participants will receive 6 cycles of Protocol Treatment [1]: 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 1 through cycle 6.
Then they will be randomly assigned (by chance, like flipping a coin) to one of the treatment groups.
This multi-center trial will be conducted in Japan. The overall time to participate in this study is approximately 20 months.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group A | Active Comparator | Panitumumab (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 | Experimental | 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 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| oxaliplatin (OXA), levofolinate calcium (l-LV), 5-FU, panitumumab | Drug | oxaliplatin (OXA), levofolinate calcium (l-LV), panitumumab: intra-venous infusion 5-FU: bolus and continuous intra-venous infusion |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Progression-Free Survival (PFS) | The PFS is the period from the date of randomization (Day 0) until the date of judgment of progression from the date of randomization, or until death by all causes, whichever comes first. 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. |
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Inclusion Criteria for enrollment:
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
Participants who are assessed at Eastern Cooperative Oncology Group (ECOG) performance status (P.S.) of 0 or 1
Life expectancy of ≥ 6 months after enrollment
Participants who have given written consent to take part in the study after detailed explanation of the study prior to enrollment
Inclusion criteria for randomization:
Exclusion Criteria for enrollment:
Exclusion criteria for randomization:
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| Name | Affiliation | Role |
|---|---|---|
| Study Director | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Nagakute | Aichi-ken | Japan | ||||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31445198 | Background | 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. | |
| 28284575 |
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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.
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Participants with a diagnosis of colorectal carcinoma were enrolled to receive protocol treatment (1) up to cycle 6 followed by randomization, received 1 out of 2 treatments from protocol treatment (2) group A and group B.
Participants took part in the study at 72 investigative sites in Japan from 16 October 2014 to 31 March 2017 (as Primary Completion Date). After that, overall study completion of this study was occurred on 31 August 2017.
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| ID | Title | Description |
|---|---|---|
| FG000 | Protocol Treatment 1 | Panitumumab (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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Protocol Treatment 1 Period |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| SAP | No | Yes | No | Statistical Analysis Plan | Dec 20, 2017 | Mar 27, 2018 |
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| oxaliplatin (OXA), levofolinate calcium (l-LV), 5-FU, panitumumab | Drug |
|
| Up to approximately 31 months |
| Overall Survival (OS) | OS was defined as the time from the day of randomization (Day 0) until death by all causes. | Up to approximately 31 months |
| Response Rate (RR) | RR was defined as the percentage of participants who had shown complete response (CR) or partial response (PR) as the best overall response in accordance with the RECIST 1.1 criteria after randomization. The best overall response was CR, followed by PR, stable disease (SD), progressive disease (PD), and not evaluable (NE). CR: disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters as the best overall response after randomization., SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD: 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). | Up to approximately 31 months |
| Time to Treatment Failure (TTF) | TTF was defined as the time from the day of randomization (Day 0) until the day of protocol treatment discontinuation determination, the day of PD decision during protocol treatment, or death from any cause, whichever came the earliest. | Up to approximately 31 months |
| Percentage of Participants With Adverse Events | Safety population was defined as all participants who received at least one dose of protocol treatment after randomization. | Up to 28 days after discontinuation of study drug or start of subsequent therapy (data cut off: 31 August 2017; Overall study completion date) |
| Percentage of Participants With Adverse Events by Severity Graded Using the Common Terminology Criteria for Adverse Events (CTCAE) Grade | An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure. Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE. | Up to 28 days after discontinuation of study drug or start of subsequent therapy (data cut off: 31 August 2017; Overall study completion date) |
| Percentage of Participants With Grade 2 or Higher Peripheral Neuropathy | Peripheral neuropathy was defined as events classified with a preferred term (PT) of "peripheral neuropathy" according to Standardized MedDRA Queries. | Up to 28 days after discontinuation of study drug or start of subsequent therapy (data cut off: 31 August 2017; Overall study completion date) |
| Percentage of Participants With Grade 3 or Higher Skin Toxicity | Skin toxicity was defined as events classified with an system organ class of "Skin and subcutaneous tissue disorders" or a preferred term of "paronychia". | Up to 28 days after discontinuation of study drug or start of subsequent therapy (data cut off: 31 August 2017; Overall study completion date) |
| Nagoya |
| Aichi-ken |
| Japan |
| Okazaki | Aichi-ken | Japan |
| Toyoaki | Aichi-ken | Japan |
| Yachiyo | Chiba | Japan |
| Kitakyushu | Fukuoka | Japan |
| Tagawa | Fukuoka | Japan |
| Aizu-Wakamatsu | Fukushima | Japan |
| Kakamigahara | Gifu | Japan |
| Tajimi | Gifu | Japan |
| Hakodate | Hokkaido | Japan |
| Kushiro | Hokkaido | Japan |
| Amagasaki | Hyōgo | Japan |
| Kakogawa | Hyōgo | Japan |
| Kobe | Hyōgo | Japan |
| Nishinomiya | Hyōgo | Japan |
| Kahoku | Ishikawa-ken | Japan |
| Kanazawa | Ishikawa-ken | Japan |
| Morioka | Iwate | Japan |
| Kida-gun | Kagawa-ken | Japan |
| Marugame | Kagawa-ken | Japan |
| Takamatsu | Kagawa-ken | Japan |
| Kawasaki | Kanagawa | Japan |
| Yokohama | Kanagawa | Japan |
| Nangoku | Kochi | Japan |
| Sendai | Miyagi | Japan |
| Matsumoto | Nagano | Japan |
| Suwa | Nagano | Japan |
| Sasebo | Nagasaki | Japan |
| Higashiosaka | Osaka | Japan |
| Hirakata | Osaka | Japan |
| Izumi | Osaka | Japan |
| Izumisano | Osaka | Japan |
| Sakai | Osaka | Japan |
| Tondabayashi | Osaka | Japan |
| Hidaka | Saitama | Japan |
| Izumo | Shimane | Japan |
| Fujioka | Shizuoka | Japan |
| Shimonoseki | Yamaguchi | Japan |
| Akita | Japan |
| Fukui | Japan |
| Fukuoka | Japan |
| Gifu | Japan |
| Hiroshima | Japan |
| Kyoto | Japan |
| Nagasaki | Japan |
| Okinawa | Japan |
| Osaka | Japan |
| Saga | Japan |
| Derived |
| Nagata 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. |
| FG001 | Protocol Treatment Period 2: Group A | Panitumumab (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. |
| FG002 | Protocol Treatment Period 2: Group B | 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 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. |
| COMPLETED |
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| NOT COMPLETED |
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| In-between Period |
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| Protocol Treatment 2 Period |
|
|
Enrolled participants included all participants who were enrolled and received protocol treatment 1.
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| ID | Title | Description |
|---|---|---|
| BG000 | Entire Study Population | Participants who received Panitumumab (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 either 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 or 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
| |||||||||||||||||
| Region of Enrollment | Number | participants |
| ||||||||||||||||||
| Histological Type of Adenocarcinoma | Count of Participants | Participants |
| ||||||||||||||||||
| Information on Primary Lesion: Single, Multiple or Unknown | Count of Participants | Participants |
| ||||||||||||||||||
| Information on Primary Lesion: Primary Lesion Site | Primary tumor location data was collected/analyzed for 124 participants with multiple choices allowed, and total 134 data was available. | Count of Participants | Participants |
| |||||||||||||||||
| History of Surgery | Count of Participants | Participants |
| ||||||||||||||||||
| History of Radiotherapy | Count of Participants | Participants |
| ||||||||||||||||||
| History of Preoperative and/or Postoperative Adjuvant (Adj) Chemotherapy (CT) | Count of Participants | Participants |
| ||||||||||||||||||
| Number of Metastatic Organs at Enrollment | Count of Participants | Participants |
| ||||||||||||||||||
| Type of Metastatic Organs at Enrollment | Count of Participants | Participants |
| ||||||||||||||||||
| Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) [Cycle 1] | ECOG assessed participant's performance status on 5 point scale: 0=Fully active/able to carry on all pre-disease activities without restriction; 1=restricted in physically strenuous activity but ambulatory/able to carry out light or sedentary work; 2=ambulatory (>50 percent of waking hours), capable of all self-care but unable to carry out any work activities; 3=capable of only limited self-care, confined to bed/chair >50 percent of waking hours; 4=completely disabled, cannot carry on any self-care, totally confined to bed/chair. | Count of Participants | Participants |
| |||||||||||||||||
| Neuroblastoma Rat Sarcoma (NRAS) + Kirsten Rat Sarcoma (KRAS) Testing | Count of Participants | Participants |
| ||||||||||||||||||
| Worst Grade of Laboratory Tests/Clinical Findings During Protocol Treatment 1 | Grade of Laboratory Tests/Clinical Findings was evaluated based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03 as follows: Grade 1 (mild); Grade 2 (moderate); Grade 3 (severe or medically significant but not immediately life threatening); Grade 4 (life-threatening consequences); Grade 5 (death related to Adverse Events (AE)). | Count of Participants | Participants |
| |||||||||||||||||
| Worst Grade of Peripheral Neuropathy During Protocol Treatment 1 | Grade of Peripheral Neuropathy was evaluated based on NCI CTCAE version 4.03 as follows: Grade 1 (mild); Grade 2 (moderate); Grade 3 (severe or medically significant but not immediately life threatening); Grade 4 (life-threatening consequences); Grade 5 (death related to AE). | Count of Participants | Participants |
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| Number of Participants without Curative Resection During Protocol Treatment 1 | Count of Participants | Participants |
| ||||||||||||||||||
| Treatment Status for Protocol Treatment 1: Reduced or Not Reduced | Treatment status was defined based on a presence or absence of any dose reduction. | Count of Participants | Participants |
| |||||||||||||||||
| Treatment Status for Protocol Treatment 1: Postponed or Not Postponed | Treatment status was defined based on a presence or absence of any dose delays. | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Full Analysis Set (FAS) was defined as all randomized participants. | Posted | Number | 80% Confidence Interval | percentage of participants | Up to 9 months after randomization |
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| Secondary | Progression-Free Survival (PFS) | The PFS is the period from the date of randomization (Day 0) until the date of judgment of progression from the date of randomization, or until death by all causes, whichever comes first. 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. | FAS was defined as all randomized participants. | Posted | Median | 95% Confidence Interval | months | Up to approximately 31 months |
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| Secondary | Overall Survival (OS) | OS was defined as the time from the day of randomization (Day 0) until death by all causes. | FAS was defined as all randomized participants. | Posted | Median | 95% Confidence Interval | months | Up to approximately 31 months |
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| Secondary | Response Rate (RR) | RR was defined as the percentage of participants who had shown complete response (CR) or partial response (PR) as the best overall response in accordance with the RECIST 1.1 criteria after randomization. The best overall response was CR, followed by PR, stable disease (SD), progressive disease (PD), and not evaluable (NE). CR: disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters as the best overall response after randomization., SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD: 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). | FAS was defined as all randomized participants. | Posted | Number | 95% Confidence Interval | percentage of participants | Up to approximately 31 months |
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| Secondary | Time to Treatment Failure (TTF) | TTF was defined as the time from the day of randomization (Day 0) until the day of protocol treatment discontinuation determination, the day of PD decision during protocol treatment, or death from any cause, whichever came the earliest. | FAS was defined as all randomized participants. | Posted | Median | 95% Confidence Interval | months | Up to approximately 31 months |
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| Secondary | Percentage of Participants With Adverse Events | Safety population was defined as all participants who received at least one dose of protocol treatment after randomization. | Safety population was defined as all participants who received at least one dose of protocol treatment after randomization. | Posted | Number | percentage of participants | Up to 28 days after discontinuation of study drug or start of subsequent therapy (data cut off: 31 August 2017; Overall study completion date) |
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| Secondary | Percentage of Participants With Adverse Events by Severity Graded Using the Common Terminology Criteria for Adverse Events (CTCAE) Grade | An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure. Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE. | Safety population was defined as all participants who received at least one dose of protocol treatment after randomization. | Posted | Number | percentage of participants | Up to 28 days after discontinuation of study drug or start of subsequent therapy (data cut off: 31 August 2017; Overall study completion date) |
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| Secondary | Percentage of Participants With Grade 2 or Higher Peripheral Neuropathy | Peripheral neuropathy was defined as events classified with a preferred term (PT) of "peripheral neuropathy" according to Standardized MedDRA Queries. | Safety population was defined as all participants who received at least one dose of protocol treatment after randomization. | Posted | Number | 95% Confidence Interval | percentage of participants | Up to 28 days after discontinuation of study drug or start of subsequent therapy (data cut off: 31 August 2017; Overall study completion date) |
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| Secondary | Percentage of Participants With Grade 3 or Higher Skin Toxicity | Skin toxicity was defined as events classified with an system organ class of "Skin and subcutaneous tissue disorders" or a preferred term of "paronychia". | Safety population was defined as all participants who received at least one dose of protocol treatment after randomization. | Posted | Number | percentage of participants | Up to 28 days after discontinuation of study drug or start of subsequent therapy (data cut off: 31 August 2017; Overall study completion date) |
|
Up to approximately 34 months
At each visit the investigators had to record any occurrence of adverse events. Adverse events were any unfavorable or unintended sign (including clinically problematic abnormalities of laboratory test data), symptoms, or diseases that developed after the administration of a drug, irrespective of whether there was a causal relationship with the relevant treatment. Safety population included participants who received at least one dose of protocol treatment after randomization.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Group A | Panitumumab (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. | 2 | 56 | 20 | 56 | 47 | 56 |
| EG001 | Group B | 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 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. | 0 | 54 | 18 | 54 | 45 | 54 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Mechanical ileus | Gastrointestinal disorders | MedDRA version 20.0 | Systematic Assessment |
| |
| Duodenal ulcer haemorrhage | Gastrointestinal disorders | MedDRA version 20.0 | Systematic Assessment |
| |
| Enterocolitis haemorrhagic | Gastrointestinal disorders | MedDRA version 20.0 | Systematic Assessment |
| |
| Intestinal obstruction | Gastrointestinal disorders | MedDRA version 20.0 | Systematic Assessment |
| |
| Inguinal hernia | Gastrointestinal disorders | MedDRA version 20.0 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA version 20.0 | Systematic Assessment |
| |
| Device related infection | Infections and infestations | MedDRA version 20.0 | Systematic Assessment |
| |
| Pelvic abscess | Infections and infestations | MedDRA version 20.0 | Systematic Assessment |
| |
| Biliary tract infection | Infections and infestations | MedDRA version 20.0 | Systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA version 20.0 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA version 20.0 | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA version 20.0 | Systematic Assessment |
| |
| Chest discomfort | General disorders | MedDRA version 20.0 | Systematic Assessment |
| |
| Death | General disorders | MedDRA version 20.0 | Systematic Assessment | One treatment emergent death occurred during the treatment and is related to treatment. |
|
| Pyrexia | General disorders | MedDRA version 20.0 | Systematic Assessment |
| |
| Hepatic failure | Hepatobiliary disorders | MedDRA version 20.0 | Systematic Assessment | One treatment emergent death occurred during the treatment and is related to treatment. |
|
| Cholangitis | Hepatobiliary disorders | MedDRA version 20.0 | Systematic Assessment |
| |
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA version 20.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA version 20.0 | Systematic Assessment |
| |
| Epilepsy | Nervous system disorders | MedDRA version 20.0 | Systematic Assessment |
| |
| Loss of consciousness | Nervous system disorders | MedDRA version 20.0 | Systematic Assessment |
| |
| Nutritional condition abnormal | Investigations | MedDRA version 20.0 | Systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA version 20.0 | Systematic Assessment |
| |
| Interstitial lung disease | Respiratory, thoracic and mediastinal disorders | MedDRA version 20.0 | Systematic Assessment |
| |
| Vertigo positional | Ear and labyrinth disorders | MedDRA version 20.0 | Systematic Assessment |
| |
| Femoral neck fracture | Injury, poisoning and procedural complications | MedDRA version 20.0 | Systematic Assessment |
| |
| Hydronephrosis | Renal and urinary disorders | MedDRA version 20.0 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA version 20.0 | Systematic Assessment |
| |
| Cancer pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 20.0 | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA version 20.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA version 20.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA version 20.0 | Systematic Assessment |
| |
| Colitis ischaemic | Gastrointestinal disorders | MedDRA version 20.0 | Systematic Assessment |
| |
| Anal fistula | Gastrointestinal disorders | MedDRA version 20.0 | Systematic Assessment |
| |
| Gastric ulcer haemorrhage | Gastrointestinal disorders | MedDRA version 20.0 | Systematic Assessment |
| |
| Ascites | Gastrointestinal disorders | MedDRA version 20.0 | Systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | MedDRA version 20.0 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA version 20.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA version 20.0 | Systematic Assessment |
| |
| Proctalgia | Gastrointestinal disorders | MedDRA version 20.0 | Systematic Assessment |
| |
| Enteritis infectious | Infections and infestations | MedDRA version 20.0 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA version 20.0 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA version 20.0 | Systematic Assessment |
| |
| Pulmonary tuberculosis | Infections and infestations | MedDRA version 20.0 | Systematic Assessment |
| |
| Transient ischaemic attack | Nervous system disorders | MedDRA version 20.0 | Systematic Assessment |
| |
| Cerebral haemorrhage | Nervous system disorders | MedDRA version 20.0 | Systematic Assessment |
| |
| Amylase increased | Investigations | MedDRA version 20.0 | Systematic Assessment |
| |
| Heat illness | Injury, poisoning and procedural complications | MedDRA version 20.0 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA version 20.0 | Systematic Assessment |
| |
| Cardiac failure congestive | Cardiac disorders | MedDRA version 20.0 | Systematic Assessment |
| |
| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | MedDRA version 20.0 | Systematic Assessment |
| |
| Embolism | Vascular disorders | MedDRA version 20.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Neutrophil count decreased | Investigations | MedDRA version 20.0 | Systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA version 20.0 | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA version 20.0 | Systematic Assessment |
| |
| Neuropathy peripheral | Nervous system disorders | MedDRA version 20.0 | Systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA version 20.0 | Systematic Assessment |
| |
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA version 20.0 | Systematic Assessment |
| |
| Paronychia | Infections and infestations | MedDRA version 20.0 | Systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA version 20.0 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA version 20.0 | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA version 20.0 | Systematic Assessment |
| |
| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | MedDRA version 20.0 | Systematic Assessment |
| |
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA version 20.0 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA version 20.0 | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA version 20.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA version 20.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA version 20.0 | Systematic Assessment |
| |
| Malaise | General disorders | MedDRA version 20.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA version 20.0 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA version 20.0 | Systematic Assessment |
| |
| Hypersensitivity | Immune system disorders | MedDRA version 20.0 | Systematic Assessment |
| |
| Interstitial lung disease | Respiratory, thoracic and mediastinal disorders | MedDRA version 20.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA version 20.0 | Systematic Assessment |
|
The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director | Takeda | +1-877-825-3327 | trialdisclosures@takeda.com |
| SAP_000.pdf |
| Prot | Yes | No | No | Study Protocol | Oct 20, 2016 | Mar 27, 2018 | Prot_001.pdf |
| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| ID | Term |
|---|---|
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D000077150 | Oxaliplatin |
| D005472 | Fluorouracil |
| D000077544 | Panitumumab |
| ID | Term |
|---|---|
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
| D014498 | Uracil |
| D011744 | Pyrimidinones |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
Not provided
Not provided
| Lack of Efficacy |
|
| Death During Protocol Treatment |
|
| Surgery Aimed at Curative Resection |
|
| Reason not specified |
|
|
| Poorly differentiated adenocarcinoma |
|
| Mucinous adenocarcinoma |
|
| Other |
|
|
| Unknown |
|
| Ascending colon |
|
|
| Transverse colon |
|
|
| Descending colon |
|
|
| Sigmoid colon |
|
|
| Rectosigmoid |
|
|
| Rectum |
|
|
|
|
| Had History of Pre/Postoperative Adj CT |
|
|
| ≥2 |
|
|
|
| Peritoneum |
|
|
| Lymph node |
|
|
| Bone |
|
|
| Adrenal gland |
|
|
| Other |
|
|
| 1 |
|
|
| Unknown |
|
| Grade 2 |
|
| Grade ≥3 |
|
| Grade 1 |
|
| Grade 2 |
|
| Grade ≥3 |
|
| Not Reduced |
|
| Not Postponed |
|
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 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. |
|
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
|
| OG001 | Group B | 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 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. |
|
|
|
|
|
|
|
| OG001 | Group B | 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 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. |
|
|
|
|
|
|