Trial Outcomes & Findings for 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 (NCT NCT02337946)

Last Updated: 2019-09-10

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

164 participants

Primary outcome timeframe

Up to 9 months after randomization

Results posted on

2019-09-10

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	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.	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.	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.
Protocol Treatment 1 Period STARTED	164	0	0
Protocol Treatment 1 Period COMPLETED	114	0	0
Protocol Treatment 1 Period NOT COMPLETED	50	0	0
In-between Period STARTED	114	0	0
In-between Period COMPLETED	113	0	0
In-between Period NOT COMPLETED	1	0	0
Protocol Treatment 2 Period STARTED	0	56	57
Protocol Treatment 2 Period Safety Population	0	56	54
Protocol Treatment 2 Period COMPLETED	0	5	7
Protocol Treatment 2 Period NOT COMPLETED	0	51	50

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.	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.
Protocol Treatment 1 Period Adverse Event	7	0	0
Protocol Treatment 1 Period Major Protocol Deviation	1	0	0
Protocol Treatment 1 Period Voluntary Withdrawal	6	0	0
Protocol Treatment 1 Period Lack of Efficacy	15	0	0
Protocol Treatment 1 Period Death During Protocol Treatment	3	0	0
Protocol Treatment 1 Period Surgery Aimed at Curative Resection	9	0	0
Protocol Treatment 1 Period Did not Meet Entrance Criteria	1	0	0
Protocol Treatment 1 Period Reason not specified	8	0	0
In-between Period Without Informed Consent	1	0	0
Protocol Treatment 2 Period Adverse Event	0	9	9
Protocol Treatment 2 Period Voluntary Withdrawal	0	3	1
Protocol Treatment 2 Period Lack of Efficacy	0	29	29
Protocol Treatment 2 Period Death During Protocol Treatment	0	1	0
Protocol Treatment 2 Period Surgery Aimed at Curative Resection	0	5	7
Protocol Treatment 2 Period Reason not specified	0	4	4

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Entire Study Population n=164 Participants 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.
Age, Continuous	66.6 years STANDARD_DEVIATION 10.3 • n=164 Participants
Sex: Female, Male Female	55 Participants n=164 Participants
Sex: Female, Male Male	109 Participants n=164 Participants
Region of Enrollment Japan	164 participants n=164 Participants
Histological Type of Adenocarcinoma Well differentiated adenocarcinoma	47 Participants n=164 Participants
Histological Type of Adenocarcinoma Moderately differentiated adenocarcinoma	91 Participants n=164 Participants
Histological Type of Adenocarcinoma Poorly differentiated adenocarcinoma	15 Participants n=164 Participants
Histological Type of Adenocarcinoma Mucinous adenocarcinoma	3 Participants n=164 Participants
Histological Type of Adenocarcinoma Other	8 Participants n=164 Participants
Information on Primary Lesion: Single, Multiple or Unknown Single	120 Participants n=164 Participants
Information on Primary Lesion: Single, Multiple or Unknown Multiple	4 Participants n=164 Participants
Information on Primary Lesion: Single, Multiple or Unknown Unknown	40 Participants n=164 Participants
Information on Primary Lesion: Primary Lesion Site Cecum	8 Participants n=124 Participants • Primary tumor location data was collected/analyzed for 124 participants with multiple choices allowed, and total 134 data was available.
Information on Primary Lesion: Primary Lesion Site Ascending colon	15 Participants n=124 Participants • Primary tumor location data was collected/analyzed for 124 participants with multiple choices allowed, and total 134 data was available.
Information on Primary Lesion: Primary Lesion Site Transverse colon	10 Participants n=124 Participants • Primary tumor location data was collected/analyzed for 124 participants with multiple choices allowed, and total 134 data was available.
Information on Primary Lesion: Primary Lesion Site Descending colon	4 Participants n=124 Participants • Primary tumor location data was collected/analyzed for 124 participants with multiple choices allowed, and total 134 data was available.
Information on Primary Lesion: Primary Lesion Site Sigmoid colon	43 Participants n=124 Participants • Primary tumor location data was collected/analyzed for 124 participants with multiple choices allowed, and total 134 data was available.
Information on Primary Lesion: Primary Lesion Site Rectosigmoid	12 Participants n=124 Participants • Primary tumor location data was collected/analyzed for 124 participants with multiple choices allowed, and total 134 data was available.
Information on Primary Lesion: Primary Lesion Site Rectum	42 Participants n=124 Participants • Primary tumor location data was collected/analyzed for 124 participants with multiple choices allowed, and total 134 data was available.
History of Surgery Had No History of Surgery	51 Participants n=164 Participants
History of Surgery Had History of Surgery	113 Participants n=164 Participants
History of Radiotherapy Had No History of Radiotherapy	163 Participants n=164 Participants
History of Radiotherapy Had History of Radiotherapy	1 Participants n=164 Participants
History of Preoperative and/or Postoperative Adjuvant (Adj) Chemotherapy (CT) Had No History of Pre/Postoperative Adj CT	151 Participants n=164 Participants
History of Preoperative and/or Postoperative Adjuvant (Adj) Chemotherapy (CT) Had History of Pre/Postoperative Adj CT	13 Participants n=164 Participants
Number of Metastatic Organs at Enrollment 0	3 Participants n=164 Participants
Number of Metastatic Organs at Enrollment 1	72 Participants n=164 Participants
Number of Metastatic Organs at Enrollment ≥2	89 Participants n=164 Participants
Type of Metastatic Organs at Enrollment Liver	119 Participants n=164 Participants
Type of Metastatic Organs at Enrollment Lung	57 Participants n=164 Participants
Type of Metastatic Organs at Enrollment Peritoneum	28 Participants n=164 Participants
Type of Metastatic Organs at Enrollment Lymph node	60 Participants n=164 Participants
Type of Metastatic Organs at Enrollment Bone	9 Participants n=164 Participants
Type of Metastatic Organs at Enrollment Adrenal gland	2 Participants n=164 Participants
Type of Metastatic Organs at Enrollment Other	13 Participants n=164 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) [Cycle 1] 0	122 Participants n=164 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) [Cycle 1] 1	42 Participants n=164 Participants
Neuroblastoma Rat Sarcoma (NRAS) + Kirsten Rat Sarcoma (KRAS) Testing Mutant-type	10 Participants n=164 Participants
Neuroblastoma Rat Sarcoma (NRAS) + Kirsten Rat Sarcoma (KRAS) Testing Wild Type (WT)	152 Participants n=164 Participants
Neuroblastoma Rat Sarcoma (NRAS) + Kirsten Rat Sarcoma (KRAS) Testing Unknown	2 Participants n=164 Participants
Worst Grade of Laboratory Tests/Clinical Findings During Protocol Treatment 1 None	103 Participants n=164 Participants
Worst Grade of Laboratory Tests/Clinical Findings During Protocol Treatment 1 Grade 2	21 Participants n=164 Participants
Worst Grade of Laboratory Tests/Clinical Findings During Protocol Treatment 1 Grade ≥3	40 Participants n=164 Participants
Worst Grade of Peripheral Neuropathy During Protocol Treatment 1 None	100 Participants n=164 Participants
Worst Grade of Peripheral Neuropathy During Protocol Treatment 1 Grade 1	51 Participants n=164 Participants
Worst Grade of Peripheral Neuropathy During Protocol Treatment 1 Grade 2	12 Participants n=164 Participants
Worst Grade of Peripheral Neuropathy During Protocol Treatment 1 Grade ≥3	1 Participants n=164 Participants
Number of Participants without Curative Resection During Protocol Treatment 1	164 Participants n=164 Participants
Treatment Status for Protocol Treatment 1: Reduced or Not Reduced Reduced	59 Participants n=164 Participants
Treatment Status for Protocol Treatment 1: Reduced or Not Reduced Not Reduced	105 Participants n=164 Participants
Treatment Status for Protocol Treatment 1: Postponed or Not Postponed Postponed	121 Participants n=164 Participants
Treatment Status for Protocol Treatment 1: Postponed or Not Postponed Not Postponed	43 Participants n=164 Participants

PRIMARY outcome

Timeframe: Up to 9 months after randomization

Population: Full Analysis Set (FAS) was defined as all randomized participants.

Outcome measures

Outcome measures
Measure	Group A n=56 Participants 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 n=57 Participants 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.
Progression-Free Survival Rate (PFS Rate) at 9 Months After Randomization	46.4 percentage of participants Interval 38.1 to 54.9	47.4 percentage of participants Interval 39.1 to 55.8

SECONDARY outcome

Timeframe: Up to approximately 31 months

Population: FAS was defined as all randomized participants.

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.

Outcome measures

Outcome measures
Measure	Group A n=56 Participants 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 n=57 Participants 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.
Progression-Free Survival (PFS)	9.1 months Interval 8.6 to 11.1	9.3 months Interval 6.0 to 13.0

SECONDARY outcome

Timeframe: Up to approximately 31 months

Population: FAS was defined as all randomized participants.

OS was defined as the time from the day of randomization (Day 0) until death by all causes.

Outcome measures

Outcome measures
Measure	Group A n=56 Participants 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 n=57 Participants 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.
Overall Survival (OS)	NA months Median and upper and lower limits of overall survival is not estimable at final analysis due to low number of participants with events.	NA months Median and upper and lower limits of overall survival is not estimable at final analysis due to low number of participants with events.

SECONDARY outcome

Timeframe: Up to approximately 31 months

Population: FAS was defined as all randomized participants.

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).

Outcome measures

Outcome measures
Measure	Group A n=56 Participants 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 n=57 Participants 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.
Response Rate (RR)	80.4 percentage of participants Interval 68.0 to 88.8	87.7 percentage of participants Interval 76.4 to 94.2

SECONDARY outcome

Timeframe: Up to approximately 31 months

Population: FAS was defined as all randomized participants.

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.

Outcome measures

Outcome measures
Measure	Group A n=56 Participants 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 n=57 Participants 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.
Time to Treatment Failure (TTF)	8.1 months Interval 5.9 to 9.5	6.1 months Interval 4.5 to 9.3

SECONDARY outcome

Timeframe: Up to 28 days after discontinuation of study drug or start of subsequent therapy (data cut off: 31 August 2017; Overall study completion date)

Population: 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.

Outcome measures

Outcome measures
Measure	Group A n=56 Participants 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 n=54 Participants 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.
Percentage of Participants With Adverse Events	100 percentage of participants	100 percentage of participants

SECONDARY outcome

Timeframe: Up to 28 days after discontinuation of study drug or start of subsequent therapy (data cut off: 31 August 2017; Overall study completion date)

Population: Safety population was defined as all participants who received at least one dose of protocol treatment after randomization.

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.

Outcome measures

Outcome measures
Measure	Group A n=56 Participants 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 n=54 Participants 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.
Percentage of Participants With Adverse Events by Severity Graded Using the Common Terminology Criteria for Adverse Events (CTCAE) Grade Grade 1	0 percentage of participants	0 percentage of participants
Percentage of Participants With Adverse Events by Severity Graded Using the Common Terminology Criteria for Adverse Events (CTCAE) Grade Grade 2	19.6 percentage of participants	27.8 percentage of participants
Percentage of Participants With Adverse Events by Severity Graded Using the Common Terminology Criteria for Adverse Events (CTCAE) Grade Grade 3, 4 and 5	80.4 percentage of participants	72.2 percentage of participants

SECONDARY outcome

Timeframe: Up to 28 days after discontinuation of study drug or start of subsequent therapy (data cut off: 31 August 2017; Overall study completion date)

Population: Safety population was defined as all participants who received at least one dose of protocol treatment after randomization.

Peripheral neuropathy was defined as events classified with a preferred term (PT) of "peripheral neuropathy" according to Standardized MedDRA Queries.

Outcome measures

Outcome measures
Measure	Group A n=56 Participants 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 n=54 Participants 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.
Percentage of Participants With Grade 2 or Higher Peripheral Neuropathy	30.4 percentage of participants Interval 19.8 to 43.4	3.7 percentage of participants Interval 0.3 to 13.3

SECONDARY outcome

Timeframe: Up to 28 days after discontinuation of study drug or start of subsequent therapy (data cut off: 31 August 2017; Overall study completion date)

Population: Safety population was defined as all participants who received at least one dose of protocol treatment after randomization.

Skin toxicity was defined as events classified with an system organ class of "Skin and subcutaneous tissue disorders" or a preferred term of "paronychia".

Outcome measures

Outcome measures
Measure	Group A n=56 Participants 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 n=54 Participants 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.
Percentage of Participants With Grade 3 or Higher Skin Toxicity Skin and subcutaneous tissue disorders	17.9 percentage of participants	18.5 percentage of participants
Percentage of Participants With Grade 3 or Higher Skin Toxicity Paronychia	7.1 percentage of participants	9.3 percentage of participants

Adverse Events

Group A

Serious events: 20 serious events

Other events: 47 other events

Deaths: 2 deaths

Group B

Serious events: 18 serious events

Other events: 45 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER