Phase I investigator-initiated clinical trial of E7820 in Japanese patients with unresectable solid tumors (CIRCUS trial)
NCCH2303 trial (CIRCUS trial)
Yamamoto Noboru
National Cancer Center Hospital
5-1-1,Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
+81-3-3542-2511
ncch2303_office@ml.res.ncc.go.jp
NCCH2303 Clinical Trial Coordinating Office
National Cancer Center Hospital
5-1-1,Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
+81-3-3542-2511
ncch2303_office@ml.res.ncc.go.jp
Recruiting
July. 24, 2024
42
Interventional
single arm study
open(masking not used)
uncontrolled control
single assignment
treatment purpose
Key inclusion criteria for both dose confirmation part and expansion part
1) Have been diagnosed with malignancy by histology or cytology (If it is conducted before registration, it may be implemented at any time.)
2) Unresectable advanced or recurrent solid tumor
3) Solid tumors refractory or intolerant to standard therapy
4) Performance Status (ECOG) is 0 or 1
5) Survival is expected to be 3 months or more from the date of enrollment
6) Age at enrollment >= 18 years
7) One or more measurable lesions on contrast enhanced CT/MRI (head/chest/abdomen/pelvis: slice thickness 5 mm or less)
8) No prior E7820 treatment.
9) Laboratory tests performed within 14 days before the enrollment date meet the following (1) to (7). However, patients should not receive Granulocyte Colony-Stimulating Factor (G-CSF) or blood transfusion within 14 days before the day of blood collection.
(1) Neutrophil count >= 1,500/mm3
(2) Platelet count >= 10 x 10000/mm3
(3) Hemoglobin >= 9.0 g/dL
(4) AST <= 75 U/L (if having hepatic metastatic disease: <=150 U/L)
(5) ALT <= Male: 105 U/L, Female: 57.5 U/L (if having hepatic metastatic disease: Male: 210 U/L, Female: 115 U/L)
(6) Total bilirubin <= 1.5 mg/dL
(7) Creatinine <= 1.5mg/dL
10) Percutaneous oxygen saturation (SpO2) of >= 92 % in room air in the 14 days prior to enrollment
11) For women of childbearing potential, they agree to use contraception and not to breastfeed from the informed consent, and for 30 days after the last dose of the investigational drug. For males, they agree to contraception from the informed consent, and for 30 days after the last dose of study treatment.
12) Patients who are able to comply with written informed consent and the protocol
Expansion part: Biliary Tract Cancer Cohort
In addition to the above 1) to 12), the patient has been diagnosed with unresectable or advanced/recurrent biliary tract cancer (intrahepatic cholangiocarcinoma, perihilar cholangiocarcinoma, distal cholangiocarcinoma, ampullary cancer, gallbladder cancer).
Expansion part: Endometrial Cancer Cohort
In addition to the above 1) to 12), the patient has been diagnosed with endometrial cancer that cannot be curatively resected or that has progressed or recurred.
Expansion part: Solid Tumor Cohort (with homologous recombination repair gene mutation)
In addition to 1) to 12) above, solid tumors in which homologous recombination repair gene mutations have been detected by either the cancer gene panel test or BRCA1 /2 genetic test or cancer gene panel test .
1) Have a history of hypersensitivity reactions to sulfonamide derivatives
2) If you are receiving anticancer drugs (chemotherapy, molecular targeted therapy, immunotherapy, etc.) within 4 weeks before registration.
3) Receipt of another investigational drug or an unapproved drug within 4 weeks before registration.
4) If you have major trauma or major surgical surgery (such as surgery with general anesthesia) within 4 weeks before registration.
5) Adverse events other than hair loss and peripheral neuropathy that were judged to be related to previous treatment have not resolved below Grade 1
6) Immunosuppressive therapy with systemic or topical steroids within 2 weeks before registration (Patients who are more than or equivalent to the prednisone 10 mg/date, or patients who are scheduled to receive these therapies)
7) Pregnant or possibly pregnant or breastfeeding women
8) If you have symptomatic brain metastasis, cancer meningitis or progressive central nervous system disease (including central nervous system degenerative disease or progressive tumor). However, patients who have completed topical treatment and discontinued adrenocortical hormone therapy 4 weeks before registration are excluded. Signs (e.g., radiographic) or symptoms should be stable during the 4 weeks before registration.
9) Spine metastases requiring radiotherapy or surgical intervention
10) With pericardial, pleural, or ascitic effusion requiring treatment
11) HIV antibody, HBs antigen, or HCV-RNA is positive (but HCV-RNA is measured only if HCV antibody is positive).
12) HBs antigen-negative, HBs antibody or HBc antibody-positive, and HBV-DNA assay-positive (not excluded if undetectable)
13) Have infections requiring systemic treatment
14) If you have a history of unstable ischemic disease (ischemic heart disease, myocardial infarction, unstable heart disease, etc.) within 3 months before enrollment.
15) Antiplatelet therapy with aspirin or anticoagulation with warfarin is indicated
16) If you have a history of active hemoptysis or gastrointestinal bleeding within 3 weeks before registration.
17) Patients with active overlapping cancers (but not (1) to (3): (1) completely resected: basal cell carcinoma, stage I squamous cell carcinoma, carcinoma in situ, carcinoma in situ, and superficial bladder cancer; (2) gastrointestinal cancer curatively resected by ESD or EMR; (3) other cancer that has not recurred for more than 5 years)
18) Echocardiography shows left heart ejection fraction (LVEF) < 50%
19) There are clinically significant ECG anomalies including QT prolongation of QTc>480ms
20) Complication or history of interstitial lung disease or pulmonary fibrosis diagnosed by imaging or clinical findings
21) Psychosis or psychiatric symptoms that interfere with daily activities are concomitant, and participation in the trial is considered difficult.
22) It is evident that there has been a history of antipsychotic use or attempted suicide within the past 2 years
23) If you have a history of drug or alcohol dependence or abuse within the past 2 years.
24) Have impaired lung function requiring aggressive treatment, including oxygen
25) The investigator determines that the patient has medical or other conditions that interfere with participation in the trial.
18age old over
No limit
Both
Patients with Unresectable advanced or recurrent solid tumors
E7820 is administered 70 mg or 100 mg orally, once daily
Solid tumor
Oral administration
D000284
Incidence of dose limiting toxicity
Pharmacokinetics / Pharmacodynamics, response rate, duration of response, time to response, disease control rate, progression-free survival, overall survival and safety
Japan Agency for Medical Research and Development
Not applicable
National Cancer Center Hospital Institutional Review Board
5-1-1,Tsukiji, Chuo-ku, Tokyo 104-0045 Japan, Tokyo
