A Phase 1 Dose Escalation Study of EOC317 in Chinese Patients With Advanced Solid Tumors

INTRODUCTION

  • Org Study ID: EOC317X1101
  • Secondary ID: N/A
  • NTC ID: NCT03583125
  • Sponsor: EddingPharm Oncology Co., LTD.

BRIEF SUMMARY


This is an open-label, single-arm phase 1, dose escalation study of EOC317 in patients with
advanced solid tumors.

DETAILED DESCRIPTION


This is an open-label, single-arm, phase 1, dose escalation study to evaluate the safety,
tolerability, pharmacokinetics, and preliminary pharmacodynamic effect of EOC317 in patients
with advanced solid tumors.

The study comprises a dose-escalation phase and a dose-expansion phase.

1. Dose-escalation: using 3+3 design to evaluate the safety, tolerability, and
pharmacokinetic profile of EOC317 at 5, 10, 20, 30, 45, 60 mg in patients with advanced
solid tumors, and to determine the maximum tolerated dose (MTD) and recommended dose
(RDE) for the dose expansion phase.

2. Dose-expansion: based on PK profile in the dose escalation phase, the dose-expansion
study will evaluate the safety, tolerability, and preliminary pharmacodynamic effect of
the RDE for EOC317 in patients with advanced solid tumors.


  • Overall Status
    Recruiting
  • Start Date
    May 29, 2018
  • Phase
    Phase 1
  • Study Type
    Interventional

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: DLT

Primary Outcome 1 - Timeframe: From the initiation of protocol treatment to the occurrence of any of the following events: disease progression or disease recurrence or death from any cause, assessed up to 12 months

CONDITION

  • Solid Tumor

ELIGIBILITY


Inclusion Criteria:

1. Patients is able to understand and willing to sign a written informed consent.

2. Patients is willing to complete the study procedure and follow-up examinations.

3. Male or female patients, 18 years old and above.

4. Dose-escalation phase: patients with histopathologically or cytopathologically
confirmed advanced malignant solid tumors, including bladder cancer,
cholangiocarcinoma, gastric cancer, breast cancer; dose-expansion phase: patients with
histopathologically or cytopathologically confirmed advanced urothelial cancer,
cholangiocarcinoma, and hepatocellular carcinoma or other advanced solid tumor with
confirmed FGFR alterations.

5. Patients who have disease progression after previous standard of care therapy, or are
unable to tolerate standard of care therapy, or have no available standard of care
therapy.

6. Dose-escalation phase: measurable or unmeasurable lesion is acceptable; dose-expansion
phase: at least one measurable lesion.

* In accordance with the response evaluation criteria in solid tumors (RECIST v1.1),
measurable lesion is defined as the lesion with the longest diameter ≥10 mm and
thickness scanned ≤5mm in CT or MRI. For lymph node lesion, its minor axis must be
≥15mm.

7. ECOG score is 0-1.

8. Expected survival is longer than 3 months.

9. No serious hematological, hepatic, or renal abnormality, in accordance with the
results of the following laboratory tests:

- Hematology: neutrophil ≥1.5x10^9/L, platelet ≥75x10^9/L, hemoglobin ≥90 g/L;

- Hepatic function: alanine aminotransferase (ALT) and aspartate aminotransferase
(AST) ≤ upper limit of normal x3.0; alkaline phosphatase (ALP) ≤ upper limit of
normal x2.5; total bilirubin (TBIL) ≤upper limit of normal x1.5; If there is a
liver tumor, hepatic function: alanine aminotransferase (ALT) and aspartate
aminotransferase (AST) ≤ upper limit of normal x5.0; If there is bone metastasis
or a liver tumor, alkaline phosphatase (ALP) ≤ upper limit of normal x5.0;

- Renal function: the creatinine clearance calculated by the Cockcroft-Gault
formula must be ≥ 50 mL/min.

10. All the adverse events is recovered to ≤ CTCAE grade 1 after previous systemic
anti-tumor therapy (except alopecia and leukodermia; stable or ≤ CTCAE grade 2
neuropathy induced by previous anti-tumor therapy).

11. Effective contraceptive measures during the treatment and within 6 months after the
last dose for male and female patients.

12. Dose-escalation phase: collection of tumor biopsy samples will be optional;
dose-expansion phase: non-optional collection of tumor biopsy samples if the FGFR
alteration is unknown during screening period;

13. Dose-expansion phase: liver function rating Child-Pugh grade A or grade B ( score ≥7);

14. Blood pressure is effectively controlled using 0 or 1 antihypertensive drugs, (blood
pressure ≤150/90 mmHg), without replacing antihypertensive drugs within 1 week before
day 1 of cycle 1;

Exclusion Criteria:

1. Previous use of the drug against FGFR pathway.

2. Having other malignant tumors other than the tumor treated in the study (exceptions:
the malignant tumors cured with no recurrence within three years before enrollment in
the study; completely resected basal cell and squamous cell carcinoma of skin;
completely resected carcinoma in situ of any type).

3. Invasion of original lesion to central nervous system (CNS) with symptoms, which is
unstable and requires high-dose steroid (≥10 mg Dexamethasone or equivalent dose) to
control it.

4. Clinically significant laboratory calcium/phosphorus abnormalities in patients even
after medical intervention before the first dose of study treatment, or in association
with parathyroid disorder or tumor lysis syndrome.

5. Ophthalmic diseases known to affect visual sensitivity, e.g., retinal/corneal/lens
lesions, severe glaucoma, et al.;

6. Active infection requiring systemic treatment (e.g., virus, bacteria, or fungus).

7. Receiving the following concomitant therapies prior to the start use of EOC317:

- Use of the drugs that can prolong QT interval and/or have the risk of torsades de
pointes (TdP) within 7 days after the first dose, for example, quinidine,
flecainide, Ibutilide;

- Use of amiodarone within 90 days prior to the first dose.

8. Cardiac impairment or clinically significant cardiovascular disease, including any of
the following:

- Cerebrovascular accident/stroke (within 6 months before enrollment);

- Myocardial infarction (within 6 months before enrollment);

- Unstable angina pectoris, congestive heart failure (New York Heart Association
classification ≥grade 2) or serious arrhythmia requiring drug therapy (including
prolonged QT interval/QTc>470 ms, pacemaker implantation); left ventricular
ejection fraction (LVEF) <50% in echocardiography.

9. History of active hemorrhage or gastrointestinal perforation risk in recent four
weeks, or unhealed wound in recent surgery.

10. Receiving the following therapies within the time period specified below prior to the
first dose :

- Anticancer therapy ≤ 4 weeks;

- Receiving other clinical trial drugs ≤ 4 weeks or ≤ 5 known half-lives (whichever
comes later); major surgery ≤4 weeks prior to the start use of investigational
product.

11. Long-term use of steroid, and daily use of ≥10 mg prednisone or equivalent dose (e.g.,
≥0.75mg dexamethasone).

12. Past history of chronic diarrhea ≥ three years or presence of diarrhea prior to the
EOC317 treatment.

13. HBsAg is positive and HBV DNA copies> normal range of detection; positive hepatitis C
antibody or HCV RNA; in patients with hepatocellular carcinoma and cholangiocarcinoma,
HBV tests show HBsAg-positive or HbcAb-positive, and HBV DNA ≥10^4 copies/ml or ≥2000
IU/ml (patients with undetectable HBV DNA after 2 weeks of standard antiviral therapy
can be enrolled), HCV RNA >10^3 copies/ml (patients with undetectable HCV RNA after 2
weeks of standard antiviral therapy can be enrolled); HbsAg and anti-HCV are both
positive at the same time;

14. History of human immunodeficiency virus infection, or other acquired, congenital
immunodeficiency disease, or history of organ transplantation.

15. Known alcohol and/or drug addiction.

16. Previous history of neurological or psychiatric/behavioral disorder, e.g., epilepsy,
history of poor compliance.

17. Female patients with positive results of pregnancy test or who are currently lactating

18. Patients who are not suitable for participation in this trial for any other reasons in
investigators' judgement.

19. Dose-expansion phase: patients with hepatic encephalopathy; moderate or severe ascites
that could not be alleviated or requiring therapeutic abdominal puncture or drainage
(confirmed by B-ultrasound or CT scan within 1 week before randomization).

Gender: All

Minimum Age: N/A

Maximum Age: 18 Years

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Hongming Pan, M.D.

Role: Study Chair

Affiliation: Sir Run Run Shaw Hospital, Zhejiang, China

Overall Contact

Name: Hongming Pan, M.D.

Phone: +86-021-3175 7928

Email: Echo.Zhao@eocpharma.com

LOCATION

Facility Status Contact
Facility: Sir Run Run Shaw Hospital
Hangzhou, Zhejiang 310016
China
Status: Recruiting Contact:
Hongming Pan, M.D