Study of D07001-Softgel Capsules in Subjects With Gastrointestinal Cancer in Dose-Escalation Phase and in Subjects With Biliary Tract Cancer in Dose-Expansion Phase

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Brief Title

Study of D07001-Softgel Capsules in Subjects With Gastrointestinal Cancer in Dose-Escalation Phase and in Subjects With Biliary Tract Cancer in Dose-Expansion Phase

Official Title

Open-Label, Multicenter Study of D07001-Softgel Capsules (Oral Gemcitabine Hydrochloride) in Subjects With Unresectable, Metastatic or Locally Advanced Gastrointestinal (GI) Cancer in Dose-Escalation Phase and in Subjects With Advanced Biliary Tract Cancer (BTC) Following Primary Chemotherapy or Combined Chemoradiotherapy (CCRT) in Dose-Expansion Phase

Brief Summary

      Part 1: Dose-Escalation Phase (Phase 1b) The primary objective is to assess the safety and
      tolerability of increasing doses of D07001 softgel in patients with unresectable locally
      advanced or metastatic gastrointestinal (GI) cancer.

      Part 2: Dose-Expansion Phase (Phase 2) The primary objective is to assess the safety and
      tolerability of D07001 softgel in patients who have achieved stable disease or better
      following first line chemotherapy or combined chemoradiotherapy (CCRT) for unresectable
      metastatic or locally advanced biliary tract cancer (BTC)
    

Detailed Description

      This open label, multicenter study will be conducted in 2 parts: a dose-escalation phase
      (Part 1) and a dose-expansion phase (Part 2).

      In both Part 1 and Part 2, eligible patients will be assigned to receive oral D07001-softgel
      on Days 1, 3, 5, 8, 10, 12, 15, 17, and 19 of a 21-day cycle (9 doses per cycle).

      Part 1: Dose Escalation Phase (Phase 1b) Part 1 of the study will follow a 3+3 dose
      escalation scheme at predefined dose levels. There will be sequential cohorts of 3 to 6
      patients each with increasing doses of 40 mg, 60 mg, 80 mg, 120 mg, and 160 mg per cohort.
      There will be no intra patient dose escalation. Cycle 1 (21 days) is defined as the dose
      limiting toxicity (DLT) assessment period.

      Part 2: Dose Expansion Phase (Phase 2) In Part 2 of the study, eligible patients will be
      randomized in a 1:1 ratio to receive D07001-softgel in an open label manner at 1 of the 2
      dose levels selected for expansion. Twenty (20) patients will be enrolled to each dose
      expansion cohort. Patients will be treated until withdrawal from treatment due to disease
      progression according to RECIST v1.1, withdrawn consent, or when another treatment
      discontinuation criterion is met. Patients who are discontinued from study drug for reasons
      other than disease progression or toxicity in the first 2 cycles of Part 2 will be replaced.
    

Study Phase

Phase 1/Phase 2

Study Type

Interventional


Primary Outcome

Part 1: Establish the maximum tolerated dose (MTD)

Secondary Outcome

 Part 1: Pharmacokinetics (PK)- maximum plasma concentration (Cmax) of gemcitabine (dFdC) and difluorodeoxyuridine (dFdU)

Condition

Gastrointestinal Cancer

Intervention

D07001-softgel capsules

Study Arms / Comparison Groups

 Part 1:Dose-Escalation Phase
Description:  40 mg D07001-softgel capsules 60 mg D07001-softgel capsules 80 mg D07001-softgel capsules 120 mg D07001-softgel capsules 160 mg D07001-softgel capsules

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

19

Start Date

August 6, 2018

Completion Date

December 29, 2020

Primary Completion Date

December 28, 2020

Eligibility Criteria

        Inclusion Criteria:

          1. Provision of a signed and dated written Informed Consent Form (ICF) prior to any study
             specific procedures

          2. Male or female patients aged 18 years or older at screening (aged 20 years or older in
             Taiwan)

          3. Histopathological or cytologic diagnosis of unresectable, metastatic or locally
             advanced GI cancer (Part 1) or unresectable metastatic or locally advanced BTC
             (cholangiocarcinoma or gallbladder cancer; Part 2)

          4. Part 1 only: Refractory to or have relapsed from all standard therapies of advanced GI
             malignancy

          5. Part 2 only:

               1. Achieved stable disease or better, based on the Investigator's assessment, in
                  response to first line systemic therapy or CCRT, with continued stable disease or
                  better based on imaging studies obtained as part of screening

               2. Completed first line systemic therapy (with 2-8 cycles of chemotherapy with a
                  gemcitabine based regimen) or CCRT, based on the local standard of care and
                  preferences in the participating countries Note: No more than 30% of patients
                  enrolled in Part 2 will have received CCRT

          6. No more than 60 days have elapsed between completion of the prior line of chemotherapy
             or CCRT and enrollment

          7. Part 2 only: Patient has not received intervening systemic therapy since first line
             treatment

          8. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0-2 in Part 1 and
             0-1 in Part 2

          9. Life expectancy is >12 weeks

         10. Adequate bone marrow function, demonstrated by:

               1. Absolute neutrophil count (ANC) ≥1,500 cell/mm3

               2. Platelet count ≥100,000 cells/mm3

               3. Hemoglobin ≥9 g/dL

         11. Adequate liver function, demonstrated by:

               1. Aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5 x upper limit of
                  normal (ULN), or ≤5.0 x ULN in the case of liver metastases

               2. Total bilirubin ≤1.5 x ULN

               3. Albumin ≥3.0 g/dL

               4. International normalized ratio (INR) <1.5

         12. Adequate renal function, demonstrated by:

               1. Serum creatinine ≤1.5 x ULN

               2. Creatinine clearance ≥ 60 mL/min calculated by Cockcroft-Gault formula or
                  directly measured with 24 hr urine collection

         13. If a woman of childbearing potential, the patient has a negative serum pregnancy test
             at screening and is not breastfeeding

         14. If a woman of childbearing potential, patient must use a medically acceptable form of
             contraception as 2 barrier methods (e.g., combination of condom, diaphragm, or
             intrauterine device), hormonal contraception (estrogen or progesterone agents) or 1
             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 must adhere to the same birth
             control methods.

         15. Patient is willing to comply with protocol-required visit schedule and visit
             requirements

        Exclusion Criteria:

          1. Part 2 only: More than one prior chemotherapy regimen for unresectable metastatic or
             locally advanced BTC Note: prior radiation (with or without radiosensitizing doses of
             chemotherapy) or fluoropyrimidine chemotherapy are allowed as postsurgical adjuvant
             therapy.

          2. Part 2 only: Received any systemic therapy (chemotherapy, biologics, immunotherapy, or
             investigational agents) for metastatic disease other than gemcitabine based
             chemotherapy or CCRT for locally advanced BTC

          3. Diagnosis of active malignancy (other than GI cancer [Part 1] or BTC [Part 2]) within
             the past 2 years, except nonmelanoma skin carcinoma and carcinoma-in-situ of uterine
             cervix treated with curative intent

          4. Prior discontinuation of gemcitabine because of pulmonary or hepatic toxicity or
             hemolytic uremic syndrome (HUS) or hypersensitivity, allergic reaction, or intolerance

          5. Any GI disorder which would significantly impede absorption of an oral agent

          6. Known brain or leptomeningeal metastases

          7. Surgery or radiation therapy within the past 28 days

          8. Part 2 only: Evidence of disease progression, based on the Investigator's assessment,
             on the screening computed tomography (CT) scan or magnetic resonance imaging (MRI)
             scan

          9. Any active disease or condition that would not permit compliance with the protocol

         10. Residual toxicity from prior chemotherapy or CCRT that is Grade ≥2 (residual Grade 2
             neuropathy and alopecia are permitted)

         11. Clinically significant cardiovascular disease (e.g., uncontrolled hypertension,
             unstable angina, congestive heart failure, or New York Heart Association [NYHA] Grade
             2 or greater), or uncontrolled serious cardiac arrhythmia

         12. Patient has a history of drug or alcohol abuse within last year

         13. Patient has documented cerebrovascular disease

         14. Patient has a seizure disorder not controlled on medication (based on decision of
             Investigator)

         15. Patient received an investigational agent within 28 days of enrollment

         16. Patients with uncontrolled active viral, bacterial, or systemic fungal infection

         17. Patient has known human immunodeficiency virus (HIV) infection

         18. Patient has hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection in
             medical history. If positive results are not indicative of true active or chronic
             infection, the patient can enter the study after discussion and agreement between the
             Investigator and the Clinical Research Organization (CRO) Medical Monitor

         19. Patient has received yellow fever vaccine or other live attenuated vaccine(s) within
             the 4 weeks prior to screening

         20. Patient has any other serious medical condition that, in the Investigator's medical
             opinion, would preclude safe participation in, and compliance with, a clinical trial
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Li-Tzong Chen, Ph. D, , 

Location Countries

Taiwan

Location Countries

Taiwan

Administrative Informations


NCT ID

NCT03531320

Organization ID

Inno-GO-03


Responsible Party

Sponsor

Study Sponsor

InnoPharmax Inc.


Study Sponsor

Li-Tzong Chen, Ph. D, Principal Investigator, National Cheng-Kung University Hospital


Verification Date

August 2021