A Phase I/II Study for the Safety and Efficacy of Panitumumab in Combination With TAS-102 for Patients With Colorectal Cancer

NCT ID: NCT02613221

Last Updated: 2019-07-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 56 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-07
• Study Completion Date: 2018-03-30

Brief Summary

The purpose of this study is to evaluate the combination of panitumumab and Triflridine/Tipiracil (FTD/TPI; TAS-102) in patients with RAS wild-type metastatic colorectal cancer (CRC) refractory to standard chemotherapy (oxaliplatin, fluoropyrimidines, irinotecan and angiogenesis inhibitors).

Detailed Description

The purpose of this study is to evaluate the combination of panitumumab and TAS-102 in patients with RAS wild-type metastatic colorectal cancer (CRC) refractory to standard chemotherapy (oxaliplatin, fluoropyrimidines, irinotecan and angiogenesis inhibitors).

Patients who are judged eligible for the study based on the inclusion and exclusion criteria will be received panitumumab (6 mg/kg) every 2 weeks and TAS-102 (35 mg/m² given orally twice a day in a 28-day) in 2-week cycle of 5 days of treatment followed by a 2-day rest period, and then a 14-day rest period.

A maximum of 58 participants will be enrolled.

Conditions

Colorectal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

panitumumab + TAS-102 combination therapy

Panitumumab 6 mg/kg every 2 weeks, plus TAS-102 35 mg/m² given orally twice a day in 5 days followed by a 2-day rest period for 2-week cycle, and then a 14-day rest period (28 days per 1 course).

Group Type: EXPERIMENTAL

Panitumumab + TAS-102

Intervention Type: DRUG

panitumumab + TAS-102 combination therapy

Interventions

Panitumumab + TAS-102

panitumumab + TAS-102 combination therapy

Intervention Type: DRUG

Other Intervention Names

Panitumumab + Triflridine/Tipiracil (FTD/TPI)

Eligibility Criteria

Inclusion Criteria

1. Investigator and subinvestigator judge a candidate is understand clinical trial and comply this protocol.

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

3. Aged ≥20 to <75 years at the time of informed consent

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

5. Participants with lesion(s) that can be evaluated. It is essential to be evaluated the tumor according to the Response Evaluation Criteria in Solid Tumors (RECIST) ver. 1.1.

6. Participants who have received chemotherapies for metastatic colorectal cancer and are refractory to or failing those chemotherapies* including; fluoropyrimidines, irinotecan, oxaliplatin, and an angiogenesis inhibitors.

*: Refractory to or failing those chemotherapies are defied as following;

• If recurrence is observed by imaging during neoadjuvant/adjuvant therapy, or within 6 months of the completion of adjuvant therapy.
• If imaging or clinical progression is observed during or within 3 months of the last dose of chemotherapy for advanced cancer.
• When it is determined that the drugs (ie, fluropyrimidines, oxaliplatin, irinotecan, and angiogenesis inhibitors) are not allowed to be resume due to intolerable AE toxicities (eg, serious allergic reaction and accumulative neuropathy).

7. Participants classified as KRAS/NRAS wild-type** by KRAS/NRAS testing*.

*: KRAS/NRAS test will be performed using the in vitro diagnostic listed in the National Health Insurance.

**: Participants with no mutation in any of the codons shown below are considered wild type.

KRAS: EXON2 (codon 12, 13), EXON3 (codon 59, 61), EXON4 (codon 117, 146) NRAS：EXON2 (codon 12, 13), EXON3 (codon 59, 61),EXON4 (codon 117, 146)

8. Participants are able to take medications orally.

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

• Neutrophil count ≥1.5×10^3/µL
• Platelet count ≥1.0×10^4/µL
• Hemoglobin ≥8.0 g/dL
• Total bilirubin ≤1.5 mg/dL
• Aspartate aminotransferase (AST) ≤ 100 IU/L ( ≤200 IU/L if liver metastases are present)
• Alanine aminotransferase (ALT) ≤ 100 IU/L ( ≤200 IU/L if liver metastases are present)
• Serum creatinine ≤ 1.5 mg/dL

10. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1

11. Life expectancy of ≥ 3 months (90 days) after enrollment

Exclusion Criteria

1. Has received anti-EGFR antibodies (cetuximab or panitumumab), regorafenib, or TAS-102.

2. Has had treatment with radiotherapy and/or chemotherapy within 2 weeks (14 days) prior to study drug administration (except for limited field radiation in order to rescue of pain).

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. Any investigational agent received within prior 4 weeks (28 days).

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

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

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

11. Serious drug hypersensitivity (without allergy to oxaliplatin)

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

13. NYHA class II or higher heart failure or serious heart disease

14. Active hepatitis B

15. Known HIV infection

16. Adverse event due to previous treatment that has not recovered to Grade 1 (Grade 2 for peripheral sensory neuropathy) by CTCAE (Japanese edition JCOG version 4.03) (excluding hemoglobin content)

17. Known BRAF mutation

18. Other participants judged by the investigator or subinvestigator to be ineligible for enrollment in the study (such as patients who were coerced to give consent)

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 74 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

Nagoya, Aichi-ken, Japan

Kashiwa, Chiba, Japan

Matsuyama, Ehime, Japan

Kitakyushu, Fukuoka, Japan

Kurume, Fukuoka, Japan

Hakodate, Hokkaido, Japan

Kushiro, Hokkaido, Japan

Sapporo, Hokkaido, Japan

Amagasaki, Hyōgo, Japan

Kobe, Hyōgo, Japan

Tsukuba, Ibaragi, Japan

Kasama, Ibaraki, Japan

Hiragi, Kagawa-ken, Japan

Sagamihara, Kanagawa, Japan

Ōsaki, Miyagi, Japan

Matsumoto, Nagano, Japan

Sasebo, Nagasaki, Japan

Yamatotakada, Nara, Japan

Takatsuki, Osaka, Japan

Shinden, Saitama, Japan

Shizuoka, Shizioka, Japan

Nakatogari, Shizuoka, Japan

Koto-ku, Tokyo, Japan

Minato-ku, Tokyo, Japan

Chiba, , Japan

Fukui, , Japan

Fukuoka, , Japan

Kumamoto, , Japan

Okayama, , Japan

Okinawa, , Japan

Osaka, , Japan

Toyama, , Japan

Countries

Japan

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

U1111-1176-3692

Identifier Type: OTHER

Identifier Source: secondary_id

JapicCTI-153076

Identifier Type: REGISTRY

Identifier Source: secondary_id

Panitumumab-1501

Identifier Type: -

Identifier Source: org_study_id