Clinical trial NCT02613221: A Phase I/II Study for the Safety and Efficacy of Panitumumab in Combination With TAS-102 for Patients With Colorectal Cancer
Official title: A Phase I/II Study for the Safety and Efficacy of Panitumumab in Combination With TAS-102 for Patients With RAS (KRAS, NRAS) Wild-type, Unresectable, Advanced/Recurrent Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Colorectal Cancer
Keywords: Metastatic colorectal cancer, Panitumumab, TAS-102
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2015-11-24
Enrollment: 56
Sex: ALL
Minimum age (years): 20
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicity (DLT) With Panitumumab Plus TAS-102 Combination Therapy
timeFrame: Up to approximately 1 month
measure: Progression Free Survival (PFS) Rate at 6 Months
timeFrame: Up to 6 months
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: From date of enrollment until the death, assessed up to approximately 29 months
measure: Progression Free Survival (PFS)
timeFrame: From date of enrollment until the date of progression or death, assessed up to approximately 29 months
measure: Response Rate (RR)
timeFrame: From date of enrollment until the end of follow-up period, assessed up to approximately 29 months
measure: Duration of Response (DOR)
timeFrame: From date of CR or PR until the date of PD or death, assessed up to approximately 29 months
measure: Disease Control Rate (DCR)
timeFrame: From date of enrollment until the end of follow-up period, assessed up to approximately 29 months
measure: Time to Treatment Failure (TTF)
timeFrame: From date of enrollment until the date of the protocol treatment discontinuation, progression or death, assessed up to approximately 29 months
measure: Number of Participants Reporting One or More Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From first dose of the study drug through 30 days after the last dose of study drug or start of subsequent antineoplastic therapy, assessed up to approximately 29 months
Other outcomes:
Locations:
city: Nagoya
country: Japan
state: Aichi
city: Kashiwa
country: Japan
state: Chiba
city: Matsuyama
country: Japan
state: Ehime
city: Kitakyushu
country: Japan
state: Fukuoka
city: Kurume
country: Japan
state: Fukuoka
city: Hakodate
country: Japan
state: Hokkaido
city: Kushiro
country: Japan
state: Hokkaido
city: Sapporo
country: Japan
state: Hokkaido
city: Amagasaki
country: Japan
state: Hyogo
city: Kobe
country: Japan
state: Hyogo
city: Tsukuba
country: Japan
state: Ibaragi
city: Kasama
country: Japan
state: Ibaraki
city: Miki
country: Japan
state: Kagawa
city: Sagamihara
country: Japan
state: Kanagawa
city: Osaki
country: Japan
state: Miyagi
city: Matsumoto
country: Japan
state: Nagano
city: Sasebo
country: Japan
state: Nagasaki
city: Yamatotakada
country: Japan
state: Nara
city: Takatsuki
country: Japan
state: Osaka
city: Ina
country: Japan
state: Saitama
city: Shizuoka
country: Japan
state: Shizioka
city: Nagaizumi
country: Japan
state: Shizuoka
city: Koto-ku
country: Japan
state: Tokyo
city: Minato-ku
country: Japan
state: Tokyo
city: Chiba
country: Japan
city: Fukui
country: Japan
city: Fukuoka
country: Japan
city: Kumamoto
country: Japan
city: Okayama
country: Japan
city: Okinawa
country: Japan
city: Osaka
country: Japan
city: Toyama
country: Japan
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: