Source: https://www.mycancergenome.org/content/clinical_trials/NCT02834780/
Timestamp: 2019-08-22 03:04:28
Document Index: 646022567

Matched Legal Cases: ['art 1', 'art 2', 'art 1', 'art 2', 'art 1', 'art 2']

Clinical Trial: NCT02834780 - My Cancer Genome
https://clinicaltrials.gov/show/NCT02834780
Brief Title: Phase 1 Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of H3B-6527 in Subjects With Advanced Hepatocellular Carcinoma
ORG STUDY ID: H3B-6527-G000-101
SECONDARY ID: 2016-001915-19
NCT ID: NCT02834780
H3B-6527 Advancedhepatocellularcarcinoma/IntrahepaticCholangiocarcinoma
The primary purpose of this study is to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of H3B-6527 (Part 1), and to assess the safety and tolerability of H3B-6527 as a single agent administered orally (Part 2) in participants with advanced hepatocellular carcinoma (HCC) or Intrahepatic Cholangiocarcinoma.
Advancedhepatocellularcarcinoma/IntrahepaticCholangiocarcinoma Experimental
1. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
2. Presence of at least one measurable lesion according to modified Response Evaluation
Criteria in Solid Tumors (mRECIST)
3. Participants with hepatocellular carcinoma or Intrahepatic Cholangiocarcinoma (ICC)
who have progressed despite standard therapy or are intolerant of standard therapy
4. Participants with HCC must have received prior sorafenib therapy. ICC participants
must have received prior platinum (cisplatin or oxaliplatin) based therapy unless
5. Prior chemotherapy, monoclonal antibody or immunotherapy (eg, tumor vaccine, cytokine,
or growth factor given to control the cancer) must have been completed at least 4
weeks before study drug administration, and all AEs have either returned to baseline
or resolved to Grade 0 or 1
6. Prior definitive radiation therapy must have been completed at least 3 weeks before
7. Tumor tissue:
1. Part 1, Dose Escalation: tumor tissue
2. Part 2, Expansion: tumor tissue
8. Measurable Disease:
1. Part 1, Dose Escalation: Participants may have measurable or non measurable
disease as defined by RECIST 1.1/mRECIST (depending on tumor type).
2. Part 2, Expansion: Participants must have measurable disease meeting the
i. Subjects with HCC: At least 1 measurable target lesion according to mRECIST
1. Hepatic lesion: The lesion can be accurately measured in at least one dimension
as ≥1.0 cm
-  The lesion is suitable for repeat measurement
-  The lesion shows intratumoral arterial phase enhancement on contrast
enhanced computed tomography (CT) or magnetic resonance imaging (MRI)
2. Nonhepatic lesion
-  Lymph node (LN) lesion that measures at least one dimension as ≥1.5 cm in
the short axis, except for porta hepatis LN that measures ≥2.0 cm in the
-  Non-nodal lesion that measures ≥1.0 cm in the longest diameter
ii.Participants with ICC:
1. At least 1 lesion of ≥1.0 cm in the longest diameter for a non-lymph node or ≥1.5
cm in the short-axis diameter for a lymph node that is serially measurable
according to RECIST 1.1 using CT/MRI.
therapies such as radiofrequency (RF) ablation or chemoembolization must show
evidence of progressive disease based on RECIST 1.1 to be deemed a target lesion.
9. Left ventricular ejection fraction (LVEF) >50% on echocardiography or multiple-gate
10. Adequate renal function defined as serum creatinine <1.5×ULN (or calculated creatinine
clearance ≥50 mL/min per the Cockcroft and Gault formula).
1. Absolute neutrophil count (ANC) ≥1500/mm3 (≥1.5×109/L)
2. Platelet counts ≥75,000/mm3 (≥75×109/L)
3. Hemoglobin ≥9.0 g/dL (may have been transfused)
12. Adequate liver function:
1. Adequate blood coagulation as evidenced by an International Normalized Ratio
2. Total bilirubin ≤1.5×ULN.
3. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤5×ULN.
4. No evidence of biliary duct obstruction unless obstruction controlled by local
treatment or, the biliary tree can be decompressed by endoscopic or percutaneous
stenting with subsequent reduction in bilirubin to ≤1.5×ULN
13. Females must not be lactating or pregnant at Screening or Baseline (as documented by a
25 IU/L or equivalent units of ß-hCG).
14. Females of childbearing potential should avoid becoming pregnant and use highly
effective contraception while on treatment and for at least 1 month after finishing
15. Willing and able to comply with all aspects of the protocol.
16. Provide written informed consent prior to any study-specific screening procedures
1. Other malignancy active within the previous 2 years except for basal or squamous cell
skin cancer, superficial bladder cancer or carcinoma in situ of the cervix or breast
that has completed curative therapy.
2. Current evidence of corneal disorder/keratopathy including but not limited to
bullous/band keratopathy, corneal abrasion, inflammation/ulceration, or
3. Participants with brain or subdural metastases are not eligible, unless they have
indication for at least 4 weeks before starting treatment in this study
4. Participants with genetic diseases of the liver that may complicate review of safety
6. Uncontrolled significant active infections, except Hepatitis B (HBV) or Hepatitis C
7. Major surgery or other loco regional treatment within 4 weeks before the first dose of
study drug or radionuclide treatment within 8 weeks
8. Inability to take oral medication, or presence of a malabsorption syndrome or any
other uncontrolled gastrointestinal condition that might impair the bioavailability of
H3B-6527. Participants with prior gastric resection are eligible
9. Participants taking any drug that is a strong inhibitor or inducer of the CYP3A4
enzyme within at least 2 weeks before the start of study drug and during the conduct
of the study unless there is an emergent or life-threatening medical condition that
10. Participants taking any drug known to prolong QTc interval within at least 2 weeks
before the start of the study drug and during the conduct of the study
11. Treatment with long-acting proton pump inhibitors that cannot be discontinued 3 days
prior to the start of study drug and during the course of the study
13. Previous treatment with a selective FGF19-FGFR4 targeted therapy and/or selective
pan-FGFR inhibitor 14. Use of any vaccines against infectious diseases (eg, influenza,
varicella) within 4 weeks (28 days) of initiation of study therapy 15. Presence of gastric
or esophageal varices requiring active treatment 16. A clinically significant ECG
abnormality, including a marked baseline prolonged QTc interval (eg, a repeated
demonstration of a QTc interval >500 ms) 17. Significant cardiovascular impairment or any
other major illness, medical condition 19. Males who have not had a successful vasectomy
(confirmed azoospermia) or they and their female partners do not meet the criteria 20.
Hypersensitivity to the study drug or to any of the excipients 21. Intolerance or
hypersensitivity to both CT and MRI contrast material that would preclude the ability to
acquire the triphasic liver imaging required by the protocol 22. Participants with
inorganic phosphorus > upper limit of normal for the institution 23. Participants with
total or ionized serum calcium > upper limit of normal for the institution 24. Participants
with endocrine changes that may result in increases in calcium or phosphate, including but
not limited to hyperparathyroidism and tumoral calcinosis 25. Participants with past
medical history and/or current evidence of tumoral calcinosis or tissue calcification 26.
Participants who take calcium, vitamin D or systemic corticosteroids
Measure: Number of Dose-limiting Toxicities (DLTs) as a function of the dose of H3B-6527 for determination of the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D)
Measure: Mean area under the plasma concentration-time curve from time 0 through the last measurable point (AUC0-t) of H3B-6527
Time Frame: For Dose Escalation Cohort: Cycle 1 on Days 1, 8, and 15. For Food Effect Cohort: Day -8, Day -1, and Days 8 and 15 of Cycle 1. For Expansion: Days 1, 8, and 15
Description: For Dose Escalation Cohort: Cycle 1 on Day 1 and Day 8 (predose [0 hours (hr)]; 0.5, 1, 2, 4, 6, 8, 10, and 24 hr (immediately prior to the next dose) postdose. Cycle 1 on Day 15 (predose [0 hr]. For Food Effect Cohort: Day -8 (predose [0 hr]; 0.5, 1, 2, 4, 6, 8, 10, and 24 hr), Day -1 (predose [0 hr]; 0.5, 1, 2, 4, 6, 8, 10, and 24 hr [immediately prior to the next dose on C1D1]); Cycle 1 on Day 8 (predose [0 hr]; 0.5, 1, 2, 4, 6, 8, 10, and 24 hr [immediately prior to the next dose]); Cycle 1 on Day 15 (predose [0 hr] only). For Expansion: Cycle 1 on Day 1 and Day 8: predose (0 hr); 0.5, 1, 2, 4, 6, 8, 10, and 24 hr (immediately prior to the next dose). Cycle 1 on Day 15: predose (0 hr).
Measure: Mean area under the plasma concentration-time curve extrapolated to infinity (AUC0-inf) of H3B-6527
Measure: Mean maximum observed plasma concentration (Cmax) of H3B-6527
Measure: Mean time of maximum observed plasma concentration (tmax) of H3B-6527
Measure: Mean accumulation ratio (Racc) of H3B-6527
Measure: Preliminary antitumor activity will be determined by using mRECIST/Response Evaluation Criteria in Solid Tumors, (RECIST) 1.1.