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A Study of L-DOS47 in Combination With Vinorelbine/Cisplatin in Lung Adenocarcinoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03891173
Recruitment Status : Recruiting
First Posted : March 26, 2019
Last Update Posted : September 13, 2019
Sponsor:
Collaborator:
KCR S.A.
Information provided by (Responsible Party):
Helix BioPharma Corporation

Brief Summary:
This study will determine the highest dose of L-DOS47 that can be given in combination with vinorelbine/cisplatin, evaluate safety and tolerability of L-DOS47 when given in combination with vinorelbine/cisplatin, and assess how effective this combination is in treating patients with lung adenocarcinoma compared to patients who are given vinorelbine/cisplatin alone.

Condition or disease Intervention/treatment Phase
Lung Adenocarcinoma Drug: L-DOS47 Drug: Cisplatin Drug: Vinorelbine Phase 2

Detailed Description:

The study is divided into two parts. In part I, the maximum tolerated dose of L-DOS47, when given in combination with vinorelbine/cisplatin, will be determined. Cohorts of 3 patients will be recruited into three dosing cohorts (6, 9 and 12 µg/kg). All patients at a given dose level must complete the first treatment cycle (3 week period) before escalation in subsequent patients can proceed. The decision for escalation to the next dose level will be made after the safety data have been reviewed by the Trial Steering Committee (TSC). If a patient in any cohort experiences a dose limiting toxicity, an additional 3 patients will be enrolled, for a maximum of up to 18 patients in this initial dose escalation part of the study.

In part II, after the maximum tolerated dose of L-DOS47 in combination with vinorelbine/cisplatin has been determined, a further 118 patients will be randomized (1:1) to receive L-DOS47 in combination with vinorelbine/cisplatin, or vinorelbine/cisplatin alone. Efficacy will be assessed by time to progression (time from first day of study drug administration to documented disease progression), response rate (proportion of patients with a best overall response of complete response and partial response using the Response Evaluation Criteria in Solid Tumours [RECIST] version 1.1 criteria), and overall survival (time from first day of study drug administration to death due to any cause). Monitoring will include radiological evaluations every second cycle. Safety and tolerability of L-DOS47 in combination will also continue to be evaluated.

For all patients, treatment will continue either until the patient experiences disease progression, unacceptable toxicity, the patient withdraws consent or has completed four treatment cycles.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 136 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Part I includes a brief initial dose escalation phase, followed by Part II, which includes a randomized treatment phase.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II, Open-Label, Randomized Study Immunoconjugate L-DOS47 in Combination With Vinorelbine/Cisplatin Versus Vinorelbine/Cisplatin Alone in Patients With Lung Adenocarcinoma
Actual Study Start Date : February 19, 2019
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : June 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: L-DOS47 in combination with cisplatin + vinorelbine
L-DOS47 (6/9/12 µg/kg) is administered by iv on Day 1 and 8 of each 21-day treatment cycle, in combination with iv administration of standard cisplatin (80 mg/m2) on Day 2 + vinorelbine (30 mg/m2) on Day 2 and 9.
Drug: L-DOS47
L-DOS47 lyophilized powder reconstituted and diluted for iv injection

Drug: Cisplatin
Cisplatin concentrate for solution for iv infusion

Drug: Vinorelbine
Vinorelbine concentrate for solution for iv infusion
Other Name: vinorelbine tartrate

Active Comparator: Cisplatin + vinorelbine alone
Administration by iv of standard Cisplatin (80 mg/m2) on Day 1 + vinorelbine (30 mg/m2) on Day 1 and 8 of each 21-day treatment cycle.
Drug: Cisplatin
Cisplatin concentrate for solution for iv infusion

Drug: Vinorelbine
Vinorelbine concentrate for solution for iv infusion
Other Name: vinorelbine tartrate




Primary Outcome Measures :
  1. Time to disease progression [ Time Frame: Up to 12 weeks ]
    Time from first day of study drug administration to documentation of disease progression (including death due to progression)


Secondary Outcome Measures :
  1. Objective response rate as measured using RECIST v. 1.1 [ Time Frame: Up to 12 weeks ]
    Proportion of patients with a best overall response of complete response and partial response

  2. Overall survival [ Time Frame: Up to 12 weeks ]
    Time to death as defined as time from first day of study drug administration to death to to any cause

  3. Safety and tolerability of L-DOS47 in combination with vinorelbine/cisplatin: Frequency of treatment emergence adverse events in patients [ Time Frame: Up to 12 weeks ]
    Frequency of treatment emergent adverse events in patients



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female aged ≥ 18 years old
  2. Histologically confirmed lung adenocarcinoma, classified as:

    • Chemotherapy-naive patients with metastatic lung adenocarcinoma for whom vinorelbine/cisplatin would be appropriate therapy;
    • metastatic recurrent lung adenocarcinoma following prior surgery, radiation and/or adjuvant chemotherapy at least 6 months ago, for whom vinorelbine/cisplatin would be appropriate therapy;
    • Staging assessed according to Tumor Node Metastases (TNM), 8th edition and based on computed tomography (CT) scan;
    • Grade 1 - 4 adenocarcinoma
  3. No prior adjuvant chemotherapy within 6 months of the first treatment day if there is recurrent disease
  4. At least a single measurable lesion in accordance with the RECIST v1.1 criteria
  5. Eastern Cooperative Oncology Group (ECOG) performance status: 0-1
  6. A life expectancy of ≥ 3 months
  7. Adequate organ function as determined by the following criteria:

    • Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L
    • Platelet count ≥ 100 × 10^9/L
    • Haemoglobin (HGB) ≥ 9 g/dL
    • Creatinine clearance ≥ 60 mL/min calculated using the Cockcroft-Gault Formula and serum creatinine ≤ 1.5 × the upper limit of normal (ULN)
    • Serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) ≤ 3 × ULN or < 5 × ULN if liver abnormalities are due to underlying malignancy
    • Total bilirubin ≤ 1.5 × ULN Note: Blood transfusions administered for the sole purpose of meeting the study inclusion criteria between the time informed consent is signed and first dose of L-DOS47 is administered are not allowed.
  8. Able to understand the information provided to them and to give written informed consent before any study activities are conducted
  9. Willing and able to comply with scheduled visits, treatment plans, laboratory tests and other study procedures
  10. Not pregnant and do not plan to become pregnant during the study. Females of childbearing potential must provide a negative pregnancy test within the Screening period (Day 21 to 0) and agree to use adequate non-hormonal contraception (which includes but is not limited to double barrier or sexual abstinence) during the study and for a period of 90 days following the last dose of study treatment. Male patients and their female partners of child-bearing potential must agree to each use an approved form of contraception during the study and for a period of 90 days following the last dose of study treatment.

Exclusion Criteria:

  1. Pregnant or nursing mother
  2. Prior history of other malignancies with the exception of non melanoma skin cancer
  3. Patients with a known positive Epidermal Growth Factor Receptor (EGFR) mutation or whose tumour harbour an anaplastic lymphoma kinase (ALK) translocation
  4. Active central nervous system metastasis and/or leptomeningeal disease (known or suspected); Patients with asymptomatic brain metastases are eligible if they had local therapy more than 1 month before enrolment
  5. Evidence of active infection
  6. Received treatment in another clinical study within the 30 days before commencing study drug and have not recovered from side effects of a study drug, except for alopecia
  7. A serious uncontrolled medical condition
  8. Known positive human immunodeficiency virus (HIV), known hepatitis B surface antigen, or hepatitis C positive
  9. Sustained QT interval corrected for heart rate (QTc) with Fridericia's correction > 450 msec at Screening, or a history of additional risk factors for Torsades de pointes (e.g., heart failure, hypokalaemia, family history of long QT syndrome)
  10. Pre-existing peripheral neuropathy Grade ≥ 1 CTCAE
  11. Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent or compliance with the requirements of the protocol
  12. Receiving chemotherapy during the 30 days before study treatment start; are receiving radiotherapy, targeted therapy, hormonal therapy, immunotherapy, major surgery or other study drugs during the 4 weeks before study treatment start, or have not recovered from all treatment related toxicities to Grade ≤ 1, except for alopecia. (Radiotherapy is allowed for the symptomatic treatment of bone metastases.)
  13. Taking systemic steroids (other than inhalers or topical steroids) or other medication to suppress the immune system
  14. Participating (or planning to participate) in any other clinical trial during this study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03891173


Contacts
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Contact: Heman Chao, Ph.D. 905-841-2300 ext 235 hchao@helixbiopharma.com
Contact: Brenda Lee, M.Sc. 416-809-2101 blee@helixbiopharma.com

Locations
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Poland
Europejskie Centrum Zdrowia Otwock Recruiting
Otwock, Poland, 05-400
Contact: Cezary Szczylik, MD, PhD    48 22 710 31 25      
Ukraine
Dnipropetrovsk City Multi-field Clinical Hospital #4 Recruiting
Dnipro, Ukraine, 49102
Contact: Igor Bondarenko, MD, PhD    +380 56 756 03 99      
Sumy Regional Clinical Oncological Centre Recruiting
Sumy, Ukraine, 40005
Contact: Andriy Kurochkin, MD    +380 54 278 13 06      
Vinnytsya Regional Clinical Oncological Centre Recruiting
Vinnytsia, Ukraine, 21029
Contact: Serhii Shevnia, MD    +380 97 279 50 74      
Sponsors and Collaborators
Helix BioPharma Corporation
KCR S.A.
Investigators
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Principal Investigator: Cezary Szczylik, MD, Ph.D. Europejskie Centrum Zdrowia Otwock
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Responsible Party: Helix BioPharma Corporation
ClinicalTrials.gov Identifier: NCT03891173    
Other Study ID Numbers: LDOS003
2016-003015-34 ( EudraCT Number )
First Posted: March 26, 2019    Key Record Dates
Last Update Posted: September 13, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Helix BioPharma Corporation:
lung adenocarcinoma
immunoconjugate
tumor microenvironment alkalinization
Additional relevant MeSH terms:
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Adenocarcinoma
Adenocarcinoma of Lung
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Vinorelbine
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action