An Exploratory Study of Treatment Sensitivity and Prognostic Factors in a Efficacy and Safety Study of mFOLFOX6 + Bevacizumab Versus mFOLFOX6 + Panitumumab Therapy in Patients With Chemotherapy-naïve Unresectable Advanced or Recurrent Colorectal Cancer

Sponsor

Takeda (Industry)

Overall Status

Completed

CT.gov ID

NCT02394834

Collaborator

(none)

757

Enrollment

151

Locations

Arms

79.6

Actual Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to investigate biomarkers which may be predictors of efficacy and safety of treatment with mFOLFOX6 + bevacizumab versus mFOLFOX6 + panitumumab therapy in patients with chemotherapy-naïve unresectable advanced or recurrent colorectal cancer.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer	Drug: oxaliplatin (OXA), levofolinate calcium (l-LV), 5-FU, panitumumab Drug: oxaliplatin (OXA), levofolinate calcium (l-LV), 5-FU, bevacizumab	Phase 3

Detailed Description

The drug being tested in this study is called Panitumumab. This exploratory study will investigate biomarkers which may be predictors of efficacy and safety of treatment with mFOLFOX6 + bevacizumab versus mFOLFOX6 + panitumumab therapy in patients with chemotherapy-naïve unresectable advanced or recurrent colorectal cancer.

Tumor tissue samples obtained from the participants who enrolled in the safety/efficacy study of Panitumumab + mFOLFOX versus bevacizumab + mFOLFOX (PARADIGM Study: NCT02394795) and provided consent for this additional study will be used. Mutations, amplification and rearrangement of predefined tumor-associated genes will be investigated using DNA collected from tumor samples used for assessing RAS mutations and plasma free DNA collected before administration of cycle 1 and at the discontinuation of the protocol treatment in the main study.

Study Design

Study Type:

Interventional

Actual Enrollment :

757 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

An Exploratory Study of Treatment Sensitivity and Prognostic Factors in a Phase III, Randomized, Controlled Study Comparing the Efficacy and Safety of mFOLFOX6 + Bevacizumab Therapy vs. mFOLFOX6 + Panitumumab Therapy in Patients With Chemotherapy-naïve Wild-type RAS(KRAS/NRAS) Unresectable Advanced or Recurrent Colorectal Cancer

Actual Study Start Date :

May 29, 2015

Actual Primary Completion Date :

Jan 14, 2022

Actual Study Completion Date :

Jan 14, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group P; mFOLFOX6 + panitumumab combination therapy OXA: 85 mg/m2/day 1 l-LV: 200 mg/m2/day 1 5-FU iv: 400 mg/m2/day 1 5-FU civ: 2400 mg/m2/day 1-3 panitumumab: 6 mg/kg mFOLFOX6 + panitumumab combination therapy, once every two weeks	Drug: oxaliplatin (OXA), levofolinate calcium (l-LV), 5-FU, panitumumab oxaliplatin (OXA), levofolinate calcium (l-LV), panitumumab: intra-venous infusion 5-FU: bolus and continuous intra-venous infusion
Active Comparator: Group B; mFOLFOX6 + bevacizumab combination therapy OXA: 85 mg/m2/day 1 l-LV: 200 mg/m2/day 1 5-FU iv: 400 mg/m2/day 1 5-FU civ: 2400 mg/m2/day 1-3 bevacizumab: 5 mg/kg/ mFOLFOX6 + bevacizumab combination therapy, once every two weeks	Drug: oxaliplatin (OXA), levofolinate calcium (l-LV), 5-FU, bevacizumab oxaliplatin (OXA), levofolinate calcium (l-LV), bevacizumab: intra-venous infusion 5-FU: bolus and continuous intra-venous infusion

Arm

Intervention/Treatment

Experimental: Group P; mFOLFOX6 + panitumumab combination therapy

OXA: 85 mg/m2/day 1 l-LV: 200 mg/m2/day 1 5-FU iv: 400 mg/m2/day 1 5-FU civ: 2400 mg/m2/day 1-3 panitumumab: 6 mg/kg mFOLFOX6 + panitumumab combination therapy, once every two weeks

Drug: oxaliplatin (OXA), levofolinate calcium (l-LV), 5-FU, panitumumab

oxaliplatin (OXA), levofolinate calcium (l-LV), panitumumab: intra-venous infusion 5-FU: bolus and continuous intra-venous infusion

Active Comparator: Group B; mFOLFOX6 + bevacizumab combination therapy

OXA: 85 mg/m2/day 1 l-LV: 200 mg/m2/day 1 5-FU iv: 400 mg/m2/day 1 5-FU civ: 2400 mg/m2/day 1-3 bevacizumab: 5 mg/kg/ mFOLFOX6 + bevacizumab combination therapy, once every two weeks

Drug: oxaliplatin (OXA), levofolinate calcium (l-LV), 5-FU, bevacizumab

oxaliplatin (OXA), levofolinate calcium (l-LV), bevacizumab: intra-venous infusion 5-FU: bolus and continuous intra-venous infusion

Outcome Measures

Primary Outcome Measures

Overall survival (OS) [Up to approximately 63 months]
OS obtained in the main study will be stratified by the presence or absence of mutation of tumor-associated genes in tumor tissues at the baseline of the main study to evaluate the relationship between OS and gene mutations. OS will be measured as the time from the date of randomization to the date of death due to any causes.

Secondary Outcome Measures

Progression-Free Survival (PFS) [Up to approximately 63 months]
PFS obtained in the main study will be stratified by the presence or absence of mutation of tumor-associated genes in tumor tissues at the baseline of the main study to evaluate the relationship between the efficacy endpoint and gene mutations. PFS is defined as the time from the date of randomization to the earlier of Progressive Disease (PD) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 or death due to any cause.
Response Rate (RR) [Approximately 12 months]
RR obtained in the main study will be stratified by the presence or absence of mutation of tumor-associated genes in tumor tissues at the baseline of the main study to evaluate the relationship between the efficacy endpoint and gene mutations. RR is defined as percentage of participants who achieve Complete Response (CR) and Partial Response (PR) as the best overall response per RECIST version 1.1.
Duration of Response (DOR) [Up to approximately 63 months]
DOR obtained in the main study will be stratified by the presence or absence of mutation of tumor-associated genes in tumor tissues at the baseline of the main study to evaluate the relationship between the efficacy endpoint and gene mutations. DOR means that the period from the day when either CR or PR is first confirmed until the day of documented PD or the day of death due to all causes, whichever occurs earlier.
Percentage of Participants who Proceeded to Surgical Resection [Up to approximately 63 month]
The outcome obtained in the main study will be stratified by the presence or absence of mutation of tumor-associated genes in tumor tissues at the baseline of the main study to evaluate the relationship between the efficacy endpoint and gene mutations.
Percentage of Participants with Early Tumor Shrinkage [Up to approximately 63 months]
The outcome obtained in the main study will be stratified by the presence or absence of mutation of tumor-associated genes in tumor tissues at the baseline of the main study to evaluate the relationship between the efficacy endpoint and gene mutations.
Degree of the Maximum Tumor Shrinkage (Depth of Response) [Up to approximately 63 months]
The outcome obtained in the main study will be stratified by the presence or absence of mutation of tumor-associated genes in tumor tissues at the baseline of the main study to evaluate the relationship between the efficacy endpoint and gene mutations.
Evaluation of the Relationship of Each Biomarker in Plasma Free DNA and Tumor Samples at Baseline of the Main Study [Up to approximately 63 months]
Evaluation of the Relationship between Each Biomarker in Plasma Free DNA at Baseline of the Main Study, and Efficacy Endpoints [Up to approximately 63 months]
Evaluation of the Relationship between a Change in Each Biomarker in Plasma Free DNA at Baseline and the Discontinuation of the Protocol Treatment of the Main Study, and Efficacy Endpoints [Up to approximately 63 months]
Evaluation of the Relationship between a Change in Each Biomarker in Tumor Tissue at Baseline and the Discontinuation of the Protocol Treatment of the Main Study, and Efficacy Endpoints [Up to approximately 63 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 79 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

(1) Patients who are enrolled in the main study and personally provided written consent after adequately explained about the contents of the additional study

Exclusion Criteria:

(1) Patients who are determined by the investigator or researchers to be not suitable for participating in the additional study

Contacts and Locations

Locations

	City	State	Country
1	Ichinomiya	Aichi	Japan
2	Komaki	Aichi	Japan
3	Kounan	Aichi	Japan
4	Nagakute	Aichi	Japan
5	Nagoya	Aichi	Japan
6	Okazaki	Aichi	Japan
7	Toyohashi	Aichi	Japan
8	Toyokawa	Aichi	Japan
9	Toyota	Aichi	Japan
10	Yatomi	Aichi	Japan
11	Daisen	Akita	Japan
12	Hirosaki	Aomori	Japan
13	Misawa	Aomori	Japan
14	Kashiwa	Chiba	Japan
15	Yachiyo	Chiba	Japan
16	Matsuyama	Ehime	Japan
17	Toon	Ehime	Japan
18	Tsuruga	Fukui	Japan
19	Yoshida	Fukui	Japan
20	Kitakyushu	Fukuoka	Japan
21	Koga	Fukuoka	Japan
22	Kurume	Fukuoka	Japan
23	Omuta	Fukuoka	Japan
24	Onga	Fukuoka	Japan
25	Aizuwakamatsu	Fukushima	Japan
26	Iwaki	Fukushima	Japan
27	Koriyama	Fukushima	Japan
28	Shirakawa	Fukushima	Japan
29	Hashima	Gifu	Japan
30	Kakamigahara	Gifu	Japan
31	Minokamo	Gifu	Japan
32	Ogaki	Gifu	Japan
33	Okazai	Gifu	Japan
34	Maebashi	Gunma	Japan
35	Ota	Gunma	Japan
36	Fukuyama	Hiroshima	Japan
37	Hakodate	Hokkaido	Japan
38	Kitami	Hokkaido	Japan
39	Kushiro	Hokkaido	Japan
40	Obihiro	Hokkaido	Japan
41	Otaru	Hokkaido	Japan
42	Sapporo	Hokkaido	Japan
43	Akashi	Hyogo	Japan
44	Amagasaki	Hyogo	Japan
45	Himeji	Hyogo	Japan
46	Kobe	Hyogo	Japan
47	Nishinomiya	Hyogo	Japan
48	Hitachi	Ibaraki	Japan
49	Kasama	Ibaraki	Japan
50	Ryugasaki	Ibaraki	Japan
51	Tsuchiura	Ibaraki	Japan
52	Tsukuba	Ibaraki	Japan
53	Hakusan	Ishikawa	Japan
54	Kaga	Ishikawa	Japan
55	Kahoku	Ishikawa	Japan
56	Kanazawa	Ishikawa	Japan
57	Nanao	Ishikawa	Japan
58	Morioka	Iwate	Japan
59	Kida	Kagawa	Japan
60	Marugame	Kagawa	Japan
61	Takamatsu	Kagawa	Japan
62	Fujisawa	Kanagawa	Japan
63	Hiratsuka	Kanagawa	Japan
64	Isehara	Kanagawa	Japan
65	Kamakura	Kanagawa	Japan
66	Kanazawa	Kanagawa	Japan
67	Sagamihara	Kanagawa	Japan
68	Yokohama	Kanagawa	Japan
69	Yokosuka	Kanagawa	Japan
70	Nankoku	Kochi	Japan
71	Matsuzaka	Mie	Japan
72	Tsu	Mie	Japan
73	Yokkaichi	Mie	Japan
74	Ishinomaki	Miyagi	Japan
75	Natori	Miyagi	Japan
76	Osaki	Miyagi	Japan
77	Sendai	Miyagi	Japan
78	Shibata	Miyagi	Japan
79	Matsumoto	Nagano	Japan
80	Saku	Nagano	Japan
81	Omura	Nagasaki	Japan
82	Sasebo	Nagasaki	Japan
83	Ikoma	Nara	Japan
84	Tenri	Nara	Japan
85	Yamatotakada	Nara	Japan
86	Yufu	Oita	Japan
87	Kurashiki	Okayama	Japan
88	Naha	Okinawa	Japan
89	Tomigusuku	Okinawa	Japan
90	Urasoe	Okinawa	Japan
91	Hirakata	Osaka	Japan
92	Kawachinagano	Osaka	Japan
93	Moriguchi	Osaka	Japan
94	Neyagawa	Osaka	Japan
95	Osakasayama	Osaka	Japan
96	Suita	Osaka	Japan
97	Takatsuki	Osaka	Japan
98	Kawagoe	Saitama	Japan
99	Kitaadachi	Saitama	Japan
100	Koshigaya	Saitama	Japan
101	Moriyama	Shiga	Japan
102	Otsu	Shiga	Japan
103	Izumi	Shimane	Japan
104	Izumo	Shimane	Japan
105	Hamamatsu	Shizuoka	Japan
106	Izunokuni	Shizuoka	Japan
107	Sunto	Shizuoka	Japan
108	Shimotsuga	Tochigi	Japan
109	Shimotsuke	Tochigi	Japan
110	Utsunomiya	Tochigi	Japan
111	Komatsushima	Tokushima	Japan
112	Bunkyo-ku	Tokyo	Japan
113	Chiyoda-ku	Tokyo	Japan
114	Chuo-ku	Tokyo	Japan
115	Itabashi-ku	Tokyo	Japan
116	Koto-ku	Tokyo	Japan
117	Machida	Tokyo	Japan
118	Minato-ku	Tokyo	Japan
119	Musashino	Tokyo	Japan
120	Shinagawa-ku	Tokyo	Japan
121	Shinjyuku-ku	Tokyo	Japan
122	Yonago	Tottori	Japan
123	Kurobe	Toyama	Japan
124	Takaoka	Toyama	Japan
125	Sakata	Yamagata	Japan
126	Tsuruoka	Yamagata	Japan
127	Iwakuni	Yamaguchi	Japan
128	Kofu	Yamanashi	Japan
129	Akita		Japan
130	Aomori		Japan
131	Chiba		Japan
132	Fukui		Japan
133	Fukuoka		Japan
134	Gifu		Japan
135	Kagoshima		Japan
136	Kochi		Japan
137	Kumamoto		Japan
138	Kyoto		Japan
139	Miyazaki		Japan
140	Nagano		Japan
141	Nagasaki		Japan
142	Niigata		Japan
143	Okayama		Japan
144	Okinawa		Japan
145	Osaka		Japan
146	Saga		Japan
147	Saitama		Japan
148	Shizuoka		Japan
149	Tokushima		Japan
150	Toyama		Japan
151	Yamagata		Japan