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

NCT03891173 | Terminated Phase 2 DMC FDA Drug

• 2 other identifiers: LDOS0032016-003015-34
• Study Type: interventional
• Target: 9
• Locations: 2 countries
• Sites: 4

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.

Conditions

Lung Adenocarcinoma

Keywords

lung adenocarcinoma; immunoconjugate; tumor microenvironment alkalinization

Outcome Measures

Primary Outcomes (1)

• Time to disease progression

  Time from first day of study drug administration to documentation of disease progression (including death due to progression)

  Up to 12 weeks

Secondary Outcomes (3)

• Objective response rate as measured using RECIST v. 1.1

  Up to 12 weeks

• Overall survival

  Up to 12 weeks

• Safety and tolerability of L-DOS47 in combination with vinorelbine/cisplatin: Frequency of treatment emergence adverse events in patients

  Up to 12 weeks

Study Arms (2)

L-DOS47 in combination with cisplatin + vinorelbine

EXPERIMENTAL

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; Drug: Cisplatin; Drug: Vinorelbine

Cisplatin + vinorelbine alone

ACTIVE COMPARATOR

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; Drug: Vinorelbine

Interventions

L-DOS47 DRUG

L-DOS47 lyophilized powder reconstituted and diluted for iv injection

L-DOS47 in combination with cisplatin + vinorelbine

Cisplatin DRUG

Cisplatin concentrate for solution for iv infusion

Cisplatin + vinorelbine alone; L-DOS47 in combination with cisplatin + vinorelbine

Vinorelbine DRUG

Vinorelbine concentrate for solution for iv infusion

Also known as: vinorelbine tartrate

Cisplatin + vinorelbine alone; L-DOS47 in combination with cisplatin + vinorelbine

Eligibility Criteria

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

You may qualify if:

• Male or female aged ≥ 18 years old
• 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
• No prior adjuvant chemotherapy within 6 months of the first treatment day if there is recurrent disease
• At least a single measurable lesion in accordance with the RECIST v1.1 criteria
• Eastern Cooperative Oncology Group (ECOG) performance status: 0-1
• A life expectancy of ≥ 3 months
• 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)

You may not qualify if:

• Pregnant or nursing mother
• Prior history of other malignancies with the exception of non melanoma skin cancer
• Patients with a known positive Epidermal Growth Factor Receptor (EGFR) mutation or whose tumour harbour an anaplastic lymphoma kinase (ALK) translocation
• 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
• Evidence of active infection
• 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
• A serious uncontrolled medical condition
• Known positive human immunodeficiency virus (HIV), known hepatitis B surface antigen, or hepatitis C positive
• 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)
• Pre-existing peripheral neuropathy Grade ≥ 1 CTCAE
• Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent or compliance with the requirements of the protocol
• 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.)
• Taking systemic steroids (other than inhalers or topical steroids) or other medication to suppress the immune system
• Participating (or planning to participate) in any other clinical trial during this study

Sponsors & Collaborators

• Helix BioPharma Corporation: lead
• KCR S.A.: collaborator

Study Sites (4)

Europejskie Centrum Zdrowia Otwock

Otwock, 05-400, Poland

Location

Dnipropetrovsk City Multi-field Clinical Hospital #4

Dnipro, 49102, Ukraine

Location

Sumy Regional Clinical Oncological Centre

Sumy, 40005, Ukraine

Location

Vinnytsya Regional Clinical Oncological Centre

Vinnytsia, 21029, Ukraine

Location

MeSH Terms

Conditions

Adenocarcinoma of Lung

Interventions

Cisplatin; Vinorelbine

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Study Officials

• Cezary Szczylik, MD, Ph.D.

  Europejskie Centrum Zdrowia Otwock

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part I includes a brief initial dose escalation phase, followed by Part II, which includes a randomized treatment phase.

Study Record Dates

• First Submitted: March 18, 2019
• First Posted: March 26, 2019
• Study Start: February 19, 2019
• Primary Completion: May 22, 2020
• Study Completion: May 22, 2020
• Last Updated: August 12, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

UA (3); PL (1)