A Phase I/II Study for the Safety and Efficacy of Panitumumab in Combination With TAS-102 for Patients With Colorectal Cancer
APOLLON
3 other identifiers
interventional
56
1 country
32
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1 colorectal-cancer
Started Dec 2015
32 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 20, 2015
CompletedFirst Posted
Study publicly available on registry
November 24, 2015
CompletedStudy Start
First participant enrolled
December 7, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 6, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
March 30, 2018
CompletedResults Posted
Study results publicly available
June 24, 2019
CompletedJuly 31, 2019
July 1, 2019
1.8 years
November 20, 2015
October 4, 2018
July 16, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Number of Participants With Dose Limiting Toxicity (DLT) With Panitumumab Plus TAS-102 Combination Therapy
DLT was evaluated according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 and was defined as any of the following events: 1. Grade 4 neutropenia for more than 7 days under maximum supportive therapy; 2. Febrile neutropenia; 3. Platelet counts decreased of Grade 3 requiring platelet transfusion or blood platelet decreased of Grade 4; 4. If Course 2 was not initiated within 14 days due to AE related to the protocol treatment; 5. Grade 3 or higher non-hematologic toxicity that was considered clinically significant, except the following cases, Grade 3 gastrointestinal symptoms that could be controlled with supportive therapy (eg, appropriate use of antiemetics, antidiarrheals), and Grade 3 or higher electrolyte abnormalities that were not deemed clinically significant.
Up to approximately 1 month
Progression Free Survival (PFS) Rate at 6 Months
PFS rate at 6 months was defined as the crude rate of surviving participants who survived or were not determined as progressive at 6 months from the day of enrollment. Although the subjects who had no imaging data on progression at 6 months after enrollment or the subjects who had lost to follow-up were included in the denominator, these subjects were not handled as progression-free. Progression included both progression disease (PD) based on diagnostic imaging assessed according to response evaluation criteria in solid tumors (RECIST) ver 1.1 and primary disease progression that cannot be confirmed by diagnostic imaging (clinical progression). 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 6 months
Secondary Outcomes (7)
Overall Survival (OS)
From date of enrollment until the death, assessed up to approximately 29 months
Progression Free Survival (PFS)
From date of enrollment until the date of progression or death, assessed up to approximately 29 months
Response Rate (RR)
From date of enrollment until the end of follow-up period, assessed up to approximately 29 months
Duration of Response (DOR)
From date of CR or PR until the date of PD or death, assessed up to approximately 29 months
Disease Control Rate (DCR)
From date of enrollment until the end of follow-up period, assessed up to approximately 29 months
- +2 more secondary outcomes
Study Arms (1)
panitumumab + TAS-102 combination therapy
EXPERIMENTALPanitumumab 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).
Interventions
panitumumab + TAS-102 combination therapy
Eligibility Criteria
You may qualify if:
- Investigator and subinvestigator judge a candidate is understand clinical trial and comply this protocol.
- Participants who have given written consent to take part in the study after detailed explanation of the study prior to enrollment
- Aged ≥20 to \<75 years at the time of informed consent
- Participants with unresectable adenocarcinoma originating in the large intestine (excluding carcinoma of the appendix and anal canal cancer)
- 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.
- 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).
- 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)
- Participants are able to take medications orally.
- +10 more criteria
You may not qualify if:
- Has received anti-EGFR antibodies (cetuximab or panitumumab), regorafenib, or TAS-102.
- 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).
- Known brain metastasis or strongly suspected of brain metastasis
- 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.).
- Body cavity fluid that requires treatment (pleural effusion, ascites, pericardial effusion, etc.)
- Participants who do not want to use contraception to prevent pregnancy, and women who are pregnant or breast-feeding, or test positive for pregnancy
- Any investigational agent received within prior 4 weeks (28 days).
- Disease requiring systemic steroids for treatment (excluding topical steroids)
- History or obvious and extensive CT findings of interstitial pulmonary disease (interstitial pneumonia, pulmonary fibrosis, etc.)
- Intestinal paralysis, gastrointestinal obstruction, or uncontrollable diarrhea (incapacitating symptoms despite adequate treatment.
- Serious drug hypersensitivity (without allergy to oxaliplatin)
- Local or systemic active infection requiring treatment, or fever indicating infection
- NYHA class II or higher heart failure or serious heart disease
- Active hepatitis B
- Known HIV infection
- +3 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Takedalead
Study Sites (32)
Unknown Facility
Nagoya, Aichi-ken, Japan
Unknown Facility
Kashiwa, Chiba, Japan
Unknown Facility
Matsuyama, Ehime, Japan
Unknown Facility
Kitakyushu, Fukuoka, Japan
Unknown Facility
Kurume, Fukuoka, Japan
Unknown Facility
Hakodate, Hokkaido, Japan
Unknown Facility
Kushiro, Hokkaido, Japan
Unknown Facility
Sapporo, Hokkaido, Japan
Unknown Facility
Amagasaki, Hyōgo, Japan
Unknown Facility
Kobe, Hyōgo, Japan
Unknown Facility
Tsukuba, Ibaragi, Japan
Unknown Facility
Kasama, Ibaraki, Japan
Unknown Facility
Hiragi, Kagawa-ken, Japan
Unknown Facility
Sagamihara, Kanagawa, Japan
Unknown Facility
Ōsaki, Miyagi, Japan
Unknown Facility
Matsumoto, Nagano, Japan
Unknown Facility
Sasebo, Nagasaki, Japan
Unknown Facility
Yamatotakada, Nara, Japan
Unknown Facility
Takatsuki, Osaka, Japan
Unknown Facility
Shinden, Saitama, Japan
Unknown Facility
Shizuoka, Shizioka, Japan
Unknown Facility
Nakatogari, Shizuoka, Japan
Unknown Facility
Koto-ku, Tokyo, Japan
Unknown Facility
Minato-ku, Tokyo, Japan
Unknown Facility
Chiba, Japan
Unknown Facility
Fukui, Japan
Unknown Facility
Fukuoka, Japan
Unknown Facility
Kumamoto, Japan
Unknown Facility
Okayama, Japan
Unknown Facility
Okinawa, Japan
Unknown Facility
Osaka, Japan
Unknown Facility
Toyama, Japan
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Director
- Organization
- Takeda
Study Officials
- STUDY DIRECTOR
Study Director
Takeda
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 20, 2015
First Posted
November 24, 2015
Study Start
December 7, 2015
Primary Completion
October 6, 2017
Study Completion
March 30, 2018
Last Updated
July 31, 2019
Results First Posted
June 24, 2019
Record last verified: 2019-07
Data Sharing
- IPD Sharing
- Will share
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.