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 ID: NCT02337946

Last Updated: 2019-09-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 164 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-10-16
• Study Completion Date: 2017-08-31

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.

Detailed Description

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.

• Group A
• Group B

This multi-center trial will be conducted in Japan. The overall time to participate in this study is approximately 20 months.

Conditions

Colorectal Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

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

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

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

Intervention Type: DRUG

Interventions

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

Intervention Type: DRUG

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Participants with unresectable adenocarcinoma originating in the large intestine (excluding carcinoma of the appendix and anal canal cancer)

2. Participants with measurable lesion(s) according to the RECIST ver. 1.1

3. 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.

4. Aged ≥ 20 years at the time of enrollment

5. 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.

6. Participants who satisfy the following criteria for the major organ function in tests performed within 14 days prior to enrollment

1. Neutrophil count ≥ 1.5 × 10^3/μL

2. White blood cell count ≥ 3.0 × 10^3/μL

3. Platelet count ≥ 10.0 × 10^4/μL

4. Hemoglobin ≥ 9.0 g/dL

5. Total bilirubin ≤ 2.0 mg/dL

6. AST ≤ 100 U/L (≤ 200 U/L if liver metastases are present)

7. ALT ≤ 100 U/L (≤ 200 U/L if liver metastases are present)

8. Serum creatinine ≤ 1.5 mg/dL

7. Participants who are assessed at Eastern Cooperative Oncology Group (ECOG) performance status (P.S.) of 0 or 1

8. Life expectancy of ≥ 6 months after enrollment

9. Participants who have given written consent to take part in the study after detailed explanation of the study prior to enrollment

1. Participants who have received 6 cycles of mFOLFOX6 + panitumumab combination therapy

2. Participants who are assessed at ECOG P.S. of 0-1 in the 6th cycle.

3. Participants for whom PD or not evaluable has been denied on the RECIST 1.1 based on imaging tests conducted after the day of administration in the 6th cycle within 14 days (2 weeks).

Exclusion Criteria

1. Radiotherapy received for a measurable lesion

2. 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.

3. Known brain metastasis or strongly suspected of brain metastasis

4. 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.).

5. Body cavity fluid that requires treatment (pleural effusion, ascites, pericardial effusion, etc.)

6. Participants who do not want to use contraception to prevent pregnancy, and women who are pregnant or breast-feeding, or test positive for pregnancy

7. Active hemorrhage requiring blood transfusion

8. Disease requiring systemic steroids for treatment (excluding topical steroids)

9. Intestinal resection and colostomy within 2 weeks prior to enrollment

10. History or obvious and extensive CT findings of interstitial pulmonary disease (interstitial pneumonia, pulmonary fibrosis, etc.)

11. Serious drug hypersensitivity

12. Local or systemic active infection requiring treatment, or fever indicating infection

13. Intestinal paralysis, gastrointestinal obstruction, or uncontrollable diarrhea (incapacitating symptoms despite adequate treatment)

14. Active hepatitis B and/or active hepatitis C

15. Known human immunodeficiency virus infection

16. Other patients judged by the investigator or subinvestigator to be ineligible for enrollment in the study

1. Participants in whom interstitial pneumonia has been newly diagnosed during the period from registration to randomization

2. Participants who have received radiotherapy during the period from registration to randomization

3. Other Participants judged by the investigator or sub-investigator to be ineligible for enrollment in the study

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Takeda

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

Nagakute, Aichi-ken, Japan

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

Countries

Japan

References

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.

Reference Type: BACKGROUND

PMID: 31445198 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 28284575 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

U1111-1161-8871

Identifier Type: REGISTRY

Identifier Source: secondary_id

183/NRP-005

Identifier Type: OTHER

Identifier Source: secondary_id

JapicCTI-142668

Identifier Type: REGISTRY

Identifier Source: secondary_id

Panitumumab-2003

Identifier Type: -

Identifier Source: org_study_id