A Trial Evaluating the Efficacy and Safety of EndoTAG®-1 in Combination With Paclitaxel and Gemcitabine Compared With Paclitaxel and Gemcitabine as First-line Therapy in Patients With Visceral Metastatic Triple-negative Breast Cancer

An Open-label, Randomized, Controlled Phase III Trial Evaluating the Efficacy and Safety of EndoTAG®-1 in Combination With Paclitaxel and Gemcitabine Compared With Paclitaxel and Gemcitabine as First-line Therapy in Patients With Visceral Metastatic Triple-negative Breast Cancer

This is a prospective, multicenter, open-label, randomized, and controlled trial to test the superiority of EndoTAG®-1 in combination with paclitaxel and gemcitabine versus paclitaxel in combination with gemcitabine.

An independent data safety monitoring board (DSMB) will be established to decide on the recommended dose (RD) of EndoTAG®-1, paclitaxel and gemcitabine to be used throughout the trial and to monitor the patients' safety and treatment efficacy data

Study Overview

• Status: Suspended
• Conditions: Triple-Negative Breast Cancer
• Intervention / Treatment: Drug: Paclitaxel; Drug: EndoTAG-1; Drug: Gemcitabine Hydrochloride

• Study Type: Interventional
• Enrollment (Anticipated): 420
• Phase: Phase 3

Contacts and Locations

Study Locations

• Taiwan
  • Kaohsiung, Taiwan
    • Kaohsiung Veterans General Hospital
  • New Taipei City, Taiwan
    • Taipei Medical University Shuang Ho Hospital
  • Taichung, Taiwan
    • Taichung Veterans General Hospital
  • Taipei, Taiwan
    • Mackay Memorial Hospital
  • Taipei, Taiwan
    • Koo Foundation Sun Yat-Sen Cancer Center
  • Taoyuan, Taiwan
    • Chang Gung Memorial Hospital, Linkou

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Gender: Female
2. Age ≥ 18 years or legal age to provide informed consent according to local regulatory requirements.

3. Metastatic TNBC confirmed histologically by a certified local laboratory (or existing medical record for confirmation is acceptable for patients in the safety run-in stage) using archival paraffinated material from the original surgery specimens or from later materials, if available. Results of the certified local laboratory must be available to allow for randomization.

   Tumors should be considered negative for ER and PrR by immunohistochemistry (IHC) (< 1% positive tumor nuclei, as per American Society of Clinical Oncology/College of American Pathologists [ASCO/CAP] guideline recommendations, Hammond et al 2010) and negative for HER2 by IHC or fluorescent or chromogenic in situ hybridization (FISH or CISH). Patients with equivocal HER2 results by IHC should have the negativity status confirmed by FISH.

4. Patients must have had prior adjuvant treatment with either sequential or concurrent anthracycline- and/or taxane-based chemotherapy. Patients may have received neoadjuvant treatment prior to the adjuvant anthracycline- and/or taxane-based chemotherapy as well.

   Note: Neoadjuvant treatment alone is acceptable only for patients in the safety run-in stage.

5. Patients with a disease-free interval (DFI) on anthracycline- and/or taxane-based adjuvant therapy of ≥ 12 months.

   Note: This criteria is for main study only.

6. Patients must be indicated for treatment with polychemotherapy for visceral metastatic disease as judged by the Investigator.

   Note: Lymph node metastasis alone is acceptable only for patients in the safety run-in stage.

7. At least one measurable or non-measurable tumor lesion according to RECIST version 1.1 as assessed by the Investigator (local radiological image assessment).
8. ECOG performance status 0 or 1.
9. Negative pregnancy test (females of childbearing potential).
10. Willingness to perform double-barrier contraception during study and for 6 months post chemotherapy treatment (females of childbearing potential).
11. Signed informed consent.

Exclusion Criteria:

1. Prior first-line chemotherapy for locally recurrent and/or metastatic breast cancer, including visceral disease.
2. Brain metastasis/known progressive cerebral metastasis (patients with cerebral metastases in a stable state or after successful surgical or radiological treatment are allowed to participate in the study).
3. Major surgery < 4 weeks prior to enrollment.
4. Cancer immunotherapy at any time.
5. Severe pulmonary obstructive or restrictive disease.
6. Uncontrolled inflammatory disease (autoimmune or infectious).
7. Clinically significant cardiac disease (New York Heart Association [NYHA] stadium > 2).

8. Results of laboratory tests (hematology, coagulation, clinical chemistry) outside specified limits:

   • White blood cell (WBC) count ≤ 3 × 109/L
   • Absolute neutrophil count (ANC) ≤ 1.5 × 109/L
   • Platelets ≤ 100 × 109/L
   • Hemoglobin (Hb) ≤ 9.0 g/dL (≤ 5.6 mmol/L)
   • Activated partial thromboplastin time/international normalized ratio (aPTT/INR) > 1.5 × upper limit of normal (ULN)
   • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT)> 2.5 × ULN (> 5 × ULN if presence of liver metastasis)
   • Alkaline phosphatase (AP) > 2 × ULN (> 5 × ULN if presence of liver metastasis)
   • Total bilirubin > 1.5 × ULN (> 2.5 × ULN if presence of liver metastasis)
9. Pregnancy or nursing status.
10. Known positive human immunodeficiency virus (HIV) infection in medical history.
11. Peripheral neuropathy associated to prior taxane therapy not recovered to grade 0 or 1.
12. Known hypersensitivity to any component of the EndoTAG®-1, standard paclitaxel and/or gemcitabine formulations.
13. History of malignancy other than breast cancer < 5 years prior to enrollment, except skin cancer (i.e., basal or squamous cell carcinoma) treated locally.
14. History of active or significant neurological disorder or psychiatric disorder that would prohibit the understanding and giving of informed consent, or would interfere in the clinical and radiological evaluation of central nervous system during the trial.
15. Concurrent treatment with other experimental products. Participation in another clinical trial with any investigational product within 30 days prior to study entry.
16. Positive test for hepatitis B (hepatitis B virus surface antigen [HBsAg] positive; or HBsAg negative but anti-hepatitis B virus core [HBc] antibody positive and HBV DNA positive) or hepatitis C (anti hepatitis C virus [HCV] antibody positive). Patients that are anti-HCV antibody positive can also be judged eligible if further HCV RNA detection shows negative results.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control	Drug: Paclitaxel; Drug: Gemcitabine Hydrochloride
Experimental: ET+P+G	Drug: Paclitaxel; Drug: EndoTAG-1; Drug: Gemcitabine Hydrochloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS	Progression free survival defined as the time from randomization to disease progression based on blinded central radiological image evaluation according to response evaluation criteria in solid tumors (RECIST, version 1.1) or death from any cause, whichever occurs first	up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	from randomization to death from any cause	24 months
Clinical benefit rate		up to 24 months
Best overall tumor response rate	objective response or SD of any duration	up to 24 months
Duration of response	the time from randomization to disease progression in the subgroup of patients responding to therapy	up to 24 months
Quality of life(QLQ-C30,QLQ-BR23)	until disease progression	up to 24 months
Post-progression PFS	as the time from start of second and subsequent lines of therapy administered after trial participation to disease progression (based on local radiological image evaluation or clinical assessment) or death from any cause, whichever occurs first	up to 12 months

Collaborators and Investigators

• Sponsor: SynCore Biotechnology Co., Ltd.
• Investigators: Principal Investigator: Tsu-Yi Chao, M.D., Ph.D., Taipei Medical University Shuang Ho Hospital, New Taipei City, Taiwan

Study record dates

Study Major Dates

• Study Start (Actual): November 23, 2016
• Primary Completion (Anticipated): March 1, 2025
• Study Completion (Anticipated): June 1, 2027

Study Registration Dates

• First Submitted: December 19, 2016
• First Submitted That Met QC Criteria: December 22, 2016
• First Posted (Estimate): December 23, 2016

Study Record Updates

• Last Update Posted (Actual): April 26, 2023
• Last Update Submitted That Met QC Criteria: April 24, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms; 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; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Gemcitabine; Paclitaxel
• Other Study ID Numbers: CT4005