An open-label Phase 1 study of E7386 in subjects with advanced solid tumors including colorectal cancer
Phase 1 study of E7386 in subjects with advanced solid tumors including colorectal cancer
Eisai Co., Ltd.
4-6-10 Koishikawa, Bunkyo-ku, Tokyo
+81-3-3817-5252
eisai-chiken_hotline@hhc.eisai.co.jp
Eisai Co., Ltd.
4-6-10 Koishikawa, Bunkyo-ku, Tokyo
+81-3-3817-5252
eisai-chiken_hotline@hhc.eisai.co.jp
completed
Mar. 05, 2019
70
Interventional
Open(masking not used)
Single Arm study
treatment purpose
1
1.Subjects with a histological and/or cytological diagnosis of solid tumor must have any of the following tumor types:
Dose Escalation part: Subjects with advanced, unresectable, or recurrent solid tumor including CRC for which no alternative standard therapy or no effective therapy exists
Expansion Part 1:
Subjects with advanced, unresectable, or recurrent CRC in third- or later-line, Or subjects with other gastrointestinal tumors such as small bowel carcinoma and gastrointestinal neuroendocrine tumors after at least 1 prior systemic chemotherapy regimen upon discussion and agreement with the sponsor.
Expansion Part 2:
Subjects with advanced, unresectable, or recurrent solid tumors expected to be highly dependent on Wnt/beta-catenin signaling pathway as specified below, who have no standard therapy. Disease progression must be confirmed within the past 12 months.
-Desmoid tumor
-Solid pseudopapillary neoplasm (SPN) of pancreas
As for subjects with solid tumors below, gene mutations should be confirmed with Sponsor-approved assays.
-Small bowel carcinoma with mutation of CTNNB1 or APC
-Adrenocortical carcinoma (ACC) with mutation of CTNNB1, APC or ZNRF3
-Solid tumors (except for CRC) with APC mutation in subjects diagnosed as familial adenomatous polyposis (FAP)
-Hepatocellular carcinoma (HCC) with CTNNB1 gain-of-function mutation
-Other types of solid tumors (except for CRC and HCC) harboring one or more Wnt-related gene mutations (e.g. APC, AXIN1, CTNNB1, RNF43, etc.) expected to be highly dependent on Wnt/beta-catenin signaling pathway based on emerging data may be enrolled upon consultation and agreement with the sponsor.
2.Life expectancy of >=12 weeks
3.Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
4.All AEs due to previous anti-cancer therapy have either returned to Grade 0-1 except for alopecia and Grade 2 peripheral neuropathy (renal/bone marrow/liver function should meet the inclusion criteria).
5.Adequate washout period before study drug administration:
Chemotherapy and radiotherapy: 3 weeks or more
Any therapy with antibody: 4 weeks or more
Any investigational drug or device: 4 weeks or more
Blood/platelet transfusion or G-CSF: 2 weeks or more
6.Adequate renal function, bone marrow function, liver function and serum mineral level
7.At least one measurable lesion based on RECIST 1.1
8.Dose escalation part: Subjects must consent to skin biopsies from skin tissue that is tumor-free during the study.
Expansion part 1: At least 5 subjects in each dose level must consent to skin biopsies from skin tissue that is tumor-free during the study. Subjects may be enrolled without skin biopsies upon consultation and agreement by the sponsor.
Expansion part 2: Subjects must consent to skin biopsies from skin tissue that is tumor-free during the study in principle. Subjects may be enrolled without consent to skin biopsies upon consultation and agreement by the sponsor.
1.Major surgery within 21 days prior to starting study drug
2.Known to be human immunodeficiency virus (HIV) positive
3.Active infection requiring systemic treatment
4.Diagnosed with meningeal carcinomatosis
5.Subjects with brain or subdural metastases are not eligible, unless they have completed local therapy and have discontinued the use of corticosteroids for this indication for at least 4 weeks before starting treatment in this study. Any signs (e.g., radiologic) or symptoms of brain metastases must be stable for at least 4 weeks before starting study treatment.
6.Pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen.
7.Any of the bone disease/conditions as follows;
- Osteoporosis with T-score of < -3.0 at the left or right total hip, left or right femoral neck or lumbar spine (L1-L4) as determined by dual energy x-ray absorptiometry (DXA) scan. Subjects with T-score <-2.5 to -3.0 and no prior medical therapy for osteoporosis can only be included provided that treatment with a bisphosphonate (eg, zoledronic acid) or denosumab has been started at least 14 days prior to the first dose of study drug.
- Metabolic bone disease, such as hyperparathyroidism, Paget's disease or osteomalacia
- Symptomatic hypercalcemia requiring bisphosphonate therapy
- History of any fracture within 6 months prior to starting study drug
- Any condition requiring orthopedic intervention
- Bone metastasis not being treated by bisphosphonate or denosumab. Subject may be included if treatment with bisphosphonate or denosumab have been started at least 14 days prior to the first dose of study drug. Subjects with previous solitary bone lesions controlled with radiotherapy are eligible
- History of symptomatic vertebral fragility fracture or any fragility fracture of the hip, pelvis, wrist or other location (defined as any fracture without a history of trauma or because of a fall from standing height or less)
- Moderate (25% to 40% decrease in the height of any vertebrae) or severe (>40% decrease in the height of any vertebrae) morphometric vertebral fracture at baseline
8.History of active malignancy (except for original disease, or definitively treated melanoma in-situ, basal or squamous cell carcinoma of the skin, carcinoma in-situ of the bladder or cervix, or early stage gastric/colorectal cancer) within the past 24 months prior to the first dose of study drug
18age old over
No limit
Both
Solid tumor, Colorectal cancer, Gastrointestinal tumor, Small bowel carcinoma, Desmoid tumor, Adrenocortical carcinoma, Solid pseudopapillary neoplasm of pancreas. Hepatocellular carcinoma
investigational material(s)
Generic name etc :E7386
INN of investigational material : -
Therapeutic category code : 429 Other antitumor agents
Dosage and Administration for Investigational material :
Dose Escalation Part : E7386(10mg or more) orally twice a day
Expansion Part 1&2 : E7386 orally twice a day based on the safety profile of Dose Escalation
control material(s)
Generic name etc :
INN of investigational material : -
Therapeutic category code :
Dosage and Administration for Investigational material :
