Solid Tumor and Intrahepatic Cholangiocarcinoma
Conditions
Interventions
experimental group (phase I):ARQ087
experimental group (phase II):ARQ087
Sponsors
Peking University Cancer Hospital & Institute
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Subjects must be able to understand and voluntarily sign the written informed consent, in which including the study medications and the relevant requirements on all of the study samples collection. 2. Men and women >= 18 years old. 3. There are no effective treatment options for subjects with advanced solid tumors as confirmed through histology or cytology (Study Stage 1 only). 4. Inoperable, recurrent or metastatic iCCA or histologically mixed tumors (hepatocyte-cholangiocarcinoma [cHCC-CCA]) as confirmed histologically or cytologically, previously treatment with at least one chemotherapy regimen (including disease progressed with adjuvant chemotherapy in 6 months) and disease progressed as confirmed imagelogical, or intolerance to first-line chemotherapy (Applicable to Stage 2). 5. FGFR2 gene fusion confirmed with a central laboratory FISH testing (Applicable to Stage 2). If possible, the above-mentioned genetic variation test can also be done for the Study Stage 1 iCCA subjects treated at Study Stage 2 target dose. For subjects planned to be enrolled in Study Stage 2, should complete the above-mentioned inclusion criteria assessment and be confirmed as FGFR2 fusion before the assessment against the following inclusion /exclusion criteria: 6. CT or MRI examination shows at least one measurable tumor lesions based on to RECIST version 1.1. The measurable tumor lesion is defined as the longest diameter >= 10 mm with the scanning thickness is not more than 5.0 mm, and the short diameter is >= 15 mm for the lymph node lesion. 7. The ECOG score is 0-1. 8. The expected life expectancy is more than 3 months. 9. No severe hematology, liver or kidney dysfunction, with the following laboratory test results met: 1) Hematology: neutrophils >= 1.5 x 10^9/L, platelets >= 75 x 10^9/L, hemoglobin >= 90 g/L; 2) Liver function: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 60 mL/min; 4) Coagulation function: international normalized ratio (INR) <= 1.5 or prothrombin time (PT) <= 1.5 x ULN or activated partial prothrombin time (APTT) <= 1.5 x ULN; 5) Urinalysis: urine protein concentration <= 1 +, without edema or serum albumin less than LLN. 10. Serum calcium and phosphorus are in the normal range (depending on the normal range of the instrument in the study site). 11. Recover to baseline or <= grade 1 adverse events from adverse event in the previous anti-tumor treatments (except for alopecia and vitiligo; neuropathy induced by the previous anti-tumor therapy changed to stable or <= grade 2). 12. The effective contraception measures should be taken by the male or fertile female subjects during treatment and within 90 days of the last dose.
Exclusion criteria
Exclusion criteria: 1. Anti-tumor treatment provided within 4 weeks or 5 half-lives of a known drug, including systemic chemotherapy, immunotherapy, hormonal therapy, targeted drug therapy, or study drug prior to the initial study treatment, whichever is longer. 2. Undergone any major surgery, topical treatment or radiation therapy within 4 weeks prior to the initial study treatment. 3. Previously treated with the drugs against the FGFR pathway, such as ponatinib, dovitinib, nintedanib, AZD4547, NVP-BGJ398, JNJ-42756493, BGJ 398, EOC 317, HMPL-453, etc. 4. Unable or unwilling to take oral ARQ 087 capsules daily. 5. Clinically unstable central nervous system (CNS) metastases (to be eligible, subjects must have stable disease >= 3 months, confirmed by magnetic resonance imaging (MRI) or computed tomography (CT) scan, and/or have CNS metastases well controlled by low-dose steroids, anti-epileptics, or other symptom- relieving medications). 6. Current evidence of corneal or retinal disorder, including but not limited to bullous/band keratopathy, keratoconjunctivitis, corneal abrasion, inflammation/ulceration, confirmed by ophthalmologic examination. 7. Medical history of or current disease of calcium and phosphorus homeostasis changes caused by parathyroid disorders, tumor lysis syndrome, etc. 8. Clinically significant medical history or current disease of ectopic calcification with the ectopic calcification sites including, but not limited to: soft tissue, kidney, intestine, myocardium, and lung, with the exception of lymph node calcification and asymptomatic coronary calcification. 9. Active hepatobiliary disease, such as viral hepatitis, cirrhosis, untreated or laparoscopic or stent placement complications, including but not limited to active cholangitis, biliary tumors, abscesses, etc. 10. History of significant cardiac disorders - Myocardial infarction or congestive heart failure within 6 months prior to study treatment (New York Heart Association Class II to IV heart disease) - Unstable angina or severe arrhythmia needs medication treatment, including QTc interval > 480 ms (male or female) - Echocardiography scan shows a left ventricular ejection fraction (LVEF) less than 50% 11. Severe gastrointestinal disease that the investigator discriminated as may affect the absorption, metabolism, or elimination of the study drug. 12. Malignant tumors within 2 years prior to the study treatment, except for the recovered or low-grade malignant tumors such as non-melanoma skin cancer, breast and cervical carcinoma in situ, superficial bladder cancer. 13. There is any of the uncontrolled diseases, including but not limited to: - Mental illness, which affects the study compliance - HIV antibody positive - Diabetic patients with poor glycemic control (Study Stage 1 only) 14. Treated with colony stimulating factor, erythropoietin, and blood transfusion etc. within 2 weeks prior to the study medication. 15. Known to have a history allergic to the components in the ARQ 087 or similar substances. 16. Blood pregnancy test positive or breastfeeding female subject. 17. The investigator concludes not applicable for participation in the study due to the other reasons.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Recommended Phase II Dose;Efficacy-objective response rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| the Safety and tolerability;pharmacokinetics (PK);progression-free survival;Duration of Response;Time To Progress;overall survival; | — |
Countries
China
Contacts
Public ContactLin Shen
Ethics Committee of Beijing Cancer Hospital
Outcome results
None listed