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

NCT03531320 | Completed Phase 1 Results FDA Drug

• 1 other identifier: Inno-GO-03
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 4

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)

Conditions

Gastrointestinal Cancer; Biliary Tract Cancer

Outcome Measures

Primary Outcomes (3)

• Part 1: Establish the Maximum Tolerated Dose (MTD)

  MTD will be defined based on the number of dose limiting toxicities (DLT) in subjects at each dose level. DLT definition: In Part 1 of the study, any of the following AEs occurring during Cycle 1 will be classified as DLTs, if there is a reasonable possibility that it is related to the study drug * Hematologic: * Grade 4 neutropenia lasting \>7 days * Febrile neutropenia (defined as neutropenia Grade ≥3 and a body temp ≥38.3°C) * Grade ≥3 neutropenic infection * Grade 4 anemia * Grade ≥3 thrombocytopenia with bleeding * Grade 4 thrombocytopenia * Non-hematologic: o Grade ≥3 toxicities that are considered clinically significant, except those that have not been maximally treated (e.g., nausea, vomiting, diarrhea\*) or can be easily treated (e.g., electrolyte abnormalities). * Failure to deliver at least 6 of the planned 9 doses during Cycle 1 due to treatment-related toxicities. * Upon the second occurrence of a toxicity leading to a dose hold.

  During Cycle 1 of treatment (each cycle is 21 days) for each subject

• Part 1 : Incidence of Adverse Events (AEs)/ Serious Adverse Event (SAEs)

  AEs will be assessed via the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03

  From date of informed consent to 30-day follow-up visit for each subject, an average of 10 months

• Part 2: Incidence of Dose Modifications, Including Dose Reduction, Interruption, or Discontinuation of Study Drug

  To measure ratio of total subjects who experienced the dose modifications including dose reduction, interruption, or discontinuation of study drug due to AEs.

  First dose through last dose for each subject, an average of 8 months

Secondary Outcomes (4)

• Part 1: Pharmacokinetics (PK)- Cmax

  Cycle 1 Days 1 and 15

• Part 1: PK- AUC

  Cycle 1 Days 1 and 15

• Part 2: Pharmacokinetics (PK)- Cmax

  Cycle 1 Days 1, 8, and 15; Cycle 1 Day 15 and Cycle 2 Day 1 for food-effect cohort only

• Part 2: PK- AUC

  Cycle 1 Days 1, 8, and 15; Cycle 1 Day 15 and Cycle 2 Day 1 for food-effect cohort only

Study Arms (2)

Part 1:Dose-Escalation Phase

EXPERIMENTAL

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

Drug: D07001-softgel capsules

Part 2: Dose-Expansion Phase (Phase 2)

EXPERIMENTAL

higher dose-expansion of D07001-softgel capsules lower dose-expansion of D07001-softgel capsules

Drug: D07001-softgel capsules

Interventions

D07001-softgel capsules DRUG

Active Ingredient:Gemcitabine hydrochloride

Part 1:Dose-Escalation Phase; Part 2: Dose-Expansion Phase (Phase 2)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of a signed and dated written Informed Consent Form (ICF) prior to any study specific procedures
• Male or female patients aged 18 years or older at screening (aged 20 years or older in Taiwan)
• 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)
• Part 1 only: Refractory to or have relapsed from all standard therapies of advanced GI malignancy
• Part 2 only:
• 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
• 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
• No more than 60 days have elapsed between completion of the prior line of chemotherapy or CCRT and enrollment
• Part 2 only: Patient has not received intervening systemic therapy since first line treatment
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0-2 in Part 1 and 0-1 in Part 2
• Life expectancy is \>12 weeks
• Adequate bone marrow function, demonstrated by:
• Absolute neutrophil count (ANC) ≥1,500 cell/mm3
• Platelet count ≥100,000 cells/mm3
• Hemoglobin ≥9 g/dL

You may not qualify if:

• 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.
• 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
• 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
• Prior discontinuation of gemcitabine because of pulmonary or hepatic toxicity or hemolytic uremic syndrome (HUS) or hypersensitivity, allergic reaction, or intolerance
• Any GI disorder which would significantly impede absorption of an oral agent
• Known brain or leptomeningeal metastases
• Surgery or radiation therapy within the past 28 days
• 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
• Any active disease or condition that would not permit compliance with the protocol
• Residual toxicity from prior chemotherapy or CCRT that is Grade ≥2 (residual Grade 2 neuropathy and alopecia are permitted)
• 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
• 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 enrollment

Sponsors & Collaborators

• InnoPharmax Inc.: lead

Study Sites (4)

China Medical University Hospital

Taichung, 404, Taiwan

Location

National Cheng-Kung University Hospital

Tainan, 704, Taiwan

Location

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

MeSH Terms

Conditions

Gastrointestinal Neoplasms; Biliary Tract Neoplasms

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Biliary Tract Diseases

Results Point of Contact

• Title: Staff of Medical Affairs
• Organization: InnoPharmax Inc.

yuan.lin@innopharmax.com

886-2-8797-7607

Study Officials

• Li-Tzong Chen, Ph. D

  National Cheng-Kung University Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part 1 of the study comprises a sequential dose escalation to identify dose-limiting toxicity (DLT) and establish the maximum tolerated dose (MTD), if any, of D07001-softgel in patients with unresectable locally advanced or metastatic GI cancer. Part 1 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. In Part 2 of the study, D07001-softgel will be administered at the 2 dose levels selected for expansion from Part 1 of the study.

Study Record Dates

• First Submitted: April 10, 2018
• First Posted: May 21, 2018
• Study Start: August 6, 2018
• Primary Completion: December 28, 2020
• Study Completion: December 29, 2020
• Last Updated: November 24, 2023
• Results First Posted: November 24, 2023

Record last verified: 2023-11

Locations

TW (4)