Phase1 Study of Gemcitabine HCl Oral Formulation(D07001-F4) in Patients With Advanced Solid Malignancies and Malignant Lymphomas

An Open Label, Phase 1, Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Clinical Activity of Gemcitabine Hydrochloride Oral Formulation(D07001-F4) in Patients With Advanced Solid Malignancies and Malignant Lymphomas

Open-label Phase 1 sequential dose-escalation study of 10 increasing doses (3 to 6 patients each)to determine and characterize the DLTs and MTD of gemcitabine HCl oral formulation (D07001-F4). Patients will be assigned to receive oral D07001-F4 on Days 1, 3, 5, 8, 10, and 12 of 4 21-day cycles each to further characterize safety and tolerability.

Study Overview

• Status: Completed
• Conditions: Advanced Solid Malignancies; Malignant Lymphomas
• Intervention / Treatment: Drug: Gemcitabine HCl Oral Formulation

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 1

Contacts and Locations

Study Locations

• Taiwan
  • Tainan, Taiwan, 704
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital
  • Taipei, Taiwan, 112
    • Taipei Veterans General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female patients aged 20 years and older
• Signed and dated informed consent form
• Patients with advanced solid malignancies and malignant lymphomas with histological or pathologic confirmation who have failed standard therapies or for which no standard therapy exists
• Both measurable and non-measurable disease allowed (measurable disease per RECIST, version 1.1, or Revised Response Criteria for Malignant Lymphoma [Cheson criteria])
• World Health Organization (WHO) performance status 0 to 2
• At least 28 days have elapsed (before screening) since the patient's prior systemic therapy, radiotherapy, or any major surgery (excluding diagnostic biopsy or venous access device placement)

• Patient has

  • Absolute neutrophil count (ANC) ≥ 1500 cells/mm³
  • Platelet count ≥ 75,000 cells/mm³
  • Hemoglobin ≥ 9 g/dL.

• Patient has adequate liver function, demonstrated by:

  • Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5*the upper limit of normal (ULN) (≤ 5.0*ULN in case of liver metastasis)
  • Total bilirubin ≤ 1.5 mg/dL (unless due to Gilbert's syndrome)
  • Albumin ≥ 2.5 g/dL
  • International normalized ratio (INR) < 1.5

• Patient has adequate renal function:

  • Serum creatinine ≤ 1.5*ULN.
• Patient has a life expectancy > 12 weeks.
• If a woman of child-bearing potential, patient has a negative pregnancy test and is not breast feeding.
• If a woman of child-bearing potential, patient is using a medically acceptable form as two barrier methods (e.g., combination of condom, diaphragm, intrauterine device), hormonal contraception (estrogen or progesterone agents) or one barrier method in combination with spermicide. Birth control is required 1 month prior to screening, for the duration of their study participation, and for 1 month after the end of the study; female partners of male patients will also adhere to similar birth control methods
• Patient is willing to comply with protocol-required visit schedule and visit requirements

Exclusion Criteria:

• Patient is receiving full-dose (therapeutic) anticoagulation therapy.
• Patient is intolerant or allergic or has a known hypersensitivity to gemcitabine
• Patient has clinically significant cardiovascular disease (for example: uncontrolled hypertension, unstable angina, congestive heart failure, or New York Heart Association Grade 2 or greater).
• Patient has uncontrolled serious cardiac arrhythmia.
• Patient has known brain metastases or any leptomeningeal metastases.
• Patient has any unresolved toxicity (>Grade 1) from previous anticancer therapy with the exception of renal and liver function which are required to be in the range as described in inclusion criteria and peripheral neuropathy acceptable if resolved to at least grade 2.
• Patient has received radiotherapy of more than 10 Gy within 6 months of screening.
• Patient has a history of drug or alcohol abuse within last year.
• Patient has documented cerebrovascular disease.
• Patient has a seizure disorder not controlled on medication (based on decision of Investigator).
• Patient received an investigational agent within 28 days of screening
• Patient received systemic treatment for infection within 14 days of screening.
• Patient has known human immunodeficiency virus (HIV) infection.
• Patient has hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection in medical history.
• Patient has received yellow fever vaccine and other live attenuated vaccines within the last 4 weeks
• Patient has any other serious medical condition that, in the Investigator's medical opinion, would preclude safe participation in a clinical trial.
• Patients have gastrointestinal disease/prior surgery that may interfere with adequate oral therapy absorption
• Patients after allogeneic stem cell transplantation
• Patients with less than 12 months from autologous stem cell transplantation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Gemcitabine HCl Oral Formulation (D07001-F4); Subjects will receive a single 5-mg (nontherapeutic) dose of gemcitabine (Gemzar®) via an IV push and then treated with Gemcitabine HCl Oral Formulation (D07001-F4)according to assigned cohort (2 mg to 80 mg) on Day 1, 3, 5, 8, 10, and 12 of 4 21-day cycles study treatment period.	Drug: Gemcitabine HCl Oral Formulation; Other Names: D07001-F4

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine MTD and DLT of Gemcitabine Oral formulation	MTD will be determined by study structure and DLT will be determined by definition	During the 21-day cycle 1 treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AE/SAE incidences	AEs will be assessed via the CTCAE version 4.03	Throughout treatment and 30-day follow-up (estimated average of 5 months)
Changes from baseline in clinical laboratory test (hematology, biochemistry, coagulation factors and urinalysis) results, vital sign measurements, physical examination findings, and ECG and 2D echocardiogram/multiple-gated acquisition (MUGA) scan results		Throughout treatment and 30-day follow-up (estimated average of 5 months)
characterize the PK of D07001-F4		cycle 0 and cycle 1 (Day -7~Day 19)
ORR(Objective Response Rate) and tumor response		After cycle 2 and cycle 4 treatments (estimated average of 2 months and 4 months)

Collaborators and Investigators

• Sponsor: InnoPharmax Inc.
• Investigators: Principal Investigator: Wu-Chou Su, MD, National Cheng-Kung University Hospital; Principal Investigator: Chia-Chi Lin, MD, National Taiwan University Hospital; Principal Investigator: Yee Chao, MD, Taipei Veterans General Hospital, Taiwan

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: February 23, 2013
• First Submitted That Met QC Criteria: February 25, 2013
• First Posted (Estimate): February 28, 2013

Study Record Updates

• Last Update Posted (Actual): July 8, 2019
• Last Update Submitted That Met QC Criteria: July 3, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Neoplasms; Lymphoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gemcitabine
• Other Study ID Numbers: HR-12-001