Evaluation of Safety and Efficacy of DCVAC/LuCa (Immunotherapy of Lung Cancer) in Patients With Metastatic Lung Cancer

A Phase I/II Study to Evaluate Safety and Efficacy of DCVAC/LuCa Added to Standard First Line ChT With Carboplatin and Paclitaxel +/- Immune Enhancers (Interferon-α and Hydroxychloroquine) vs ChT Alone in Patients With Stage IV NSCLC

The purpose of the study is to compare efficacy of DCVAC/LuCa + chemotherapy +/- immune enhancers vs. chemotherapy alone in patients with stage IV NSCLC, as measured by progression free survival (PFS).

Study Overview

• Status: Completed
• Conditions: Stage IV Non-small Cell Lung Cancer
• Intervention / Treatment: Biological: DCVAC add on to SOC; Biological: DCVAC and immune enhancers add on to SOC; Other: Standard of Care Chemotherapy

Detailed Description

The purpose of the study is to compare efficacy of DCVAC/LuCa + chemotherapy +/- immune enhancers vs. Standard of Care chemotherapy alone in patients with stage IV NSCLC, as measured by progression free survival (PFS).

• Study Type: Interventional
• Enrollment (Anticipated): 105
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Czechia
  • Brno, Czechia, 625 00
  • Hradec Kralove, Czechia, 500 05
  • Jindřichův Hradec, Czechia, 377 38
  • Kutna Hora, Czechia, 284 01
  • Nachod, Czechia, 547 69
  • Olomouc, Czechia, 775 20
  • Ostrava, Czechia, 708 52
  • Pardubice, Czechia, 530 03
  • Plzen, Czechia, 305 99
  • Praha, Czechia, 128 08
  • Praha, Czechia, 140 59
  • Praha, Czechia, 150 06
  • Pribram, Czechia, 261 95
  • Usti nad Labem, Czechia, 401 13
  • Zlin, Czechia, 762 75
• Slovakia
  • Kosice, Slovakia, 040 01
  • Piest'any, Slovakia, 921 01
  • Poprad, Slovakia, 058 01

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Histologically or cytologically confirmed non-small cell lung cancer (NSCLC) of either adenomatous or squamous cell carcinoma differentiation; mixed tumors will be categorized by the predominant cell type.
2. Advanced NSCLC (stage IV unresectable disease)
3. Patients must have measurable or non-measurable disease
4. Patients (male and female) ≥ 18 years
5. Eastern Cooperative Oncology Group (ECOG) Performance status 0-1 6. Patients must have recovered from toxicity of any prior therapy (e.g. surgery, radiotherapy, or therapy for other diseases than NSCLC). Recovery is defined as less than or equal to grade 2 toxicity according (except alopecia) to NCI CTCAE 7. Laboratory criteria 7.1 Platelet count of at least 100,000/mm3 (100 x 109/L) 7.2 White blood cells (WBC) greater than 4,000/mm3 (4.0 x109/L) 7.3 Hemoglobin (Hb) at least 9g/dL (90 g/L) 7.4 Total bilirubin levels ≤1.5mg/dL (benign hereditary hyper-bilirubinemias, e.g., Gilbert´s syndrome are permitted) 7.5 Serum alanine aminotransferase and aspartate aminotransferase ≤ 5 times the upper limit of normal (ULN) 7.6 Serum creatinine ≤ 1.5 times the upper limit of normal (ULN)

8. Women of childbearing potential and sexually active males must agree to use an accepted and effective method of contraception (hormonal or barrier methods, abstinence) prior to study entry and for the duration of the treatment plus 3 months.

9. Signed informed consent including patient's ability to comprehend its contents. (Consent to genetic testing is not a condition for participation in the clinical trial)

Exclusion Criteria:

1. Prior chemotherapy for stage IV NSCLC
2. Immunotherapy, monoclonal antibodies received within 4 weeks prior to randomization
3. Patients comorbidities 3.1 Patients who are not indicated for chemotherapy treatment with first line Standard of Care chemotherapy (carboplatin/paclitaxel) 3.2 Active other malignancy than NSCLC 3.3 Known central nervous system (CNS) metastases 3.4 Any disease requiring chronic steroid or immunosuppressive therapy 3.5 HIV positive 3.6 Active hepatitis B (HBV) and/or C (HCV), active syphilis 3.7 Ongoing/active significant infection or other severe medical condition 3.8 Pre-existing thyroid disease unless it can be controlled with conventional treatment 3.9 Clinically significant cardiovascular disease including: 3.9.1 Uncontrolled congestive heart failure 3.9.2 Unstable angina pectoris 3.9.3 Uncontrolled severe cardiac arrhythmia 3.9.4 Myocardial infarction within 6 months prior randomization 3.10 Psychiatric illness/social situations that would limit compliance with study requirements
4. Pregnant or breast feeding women
5. Participation in a clinical trial using experimental therapy within the last 4 weeks prior to randomization
6. Contra indications to treatment with hydroxychloroquine, known G6PD deficiency (anamnestic information, no test necessary) and psoriasis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DCVAC add on to SOC; Combination therapy with DCVAC and Standard of Care (Carboplatin, Paclitaxel)	Biological: DCVAC add on to SOC; DCVAC add on to SOC (Carboplatin, Paclitaxel): until progression or intolerance or death
Experimental: DCVAC and immune enhancers add on to SOC; Combination therapy with DCVAC, immune enhancers (Interferon-α, Hydroxychloroquine) and Standard of Care (Carboplatin, Paclitaxel)	Biological: DCVAC and immune enhancers add on to SOC; DCVAC +/- immune enhancers (Interferon-α and Hydroxychloroquine) add on to SOC (Carboplatin, Paclitaxel): until progression or intolerance or death
Other: Standard of Care Chemotherapy; Standard of Care chemotherapy (Carboplatin, Paclitaxel)	Other: Standard of Care Chemotherapy; SOC (Carboplatin, Paclitaxel): until progression or intolerance or death

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Comparison efficacy of DCVAC/LuCa + chemotherapy +/- immune enhancers vs. chemotherapy alone in patients with stage IV NSCLC, as measured by progression free survival (PFS).	17 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Comparison of safety in patients treated with DCVAC/LuCa + chemotherapy +/- immune enhancers vs. chemotherapy alone. (AEs, SAEs, laboratory abnormalities, vital signs)	17 months
Further comparison of efficacy of DCVAC/LuCa + chemotherapy +/- immune enhancers vs. chemotherapy alone, as measured by objective response rate and duration of response (per RECIST 1.1).	17 months
Further comparison of efficacy of DCVAC/LuCa + chemotherapy +/- immune enhancers vs. chemotherapy alone, as measured by overall survival.	17 months

Collaborators and Investigators

• Sponsor: SOTIO a.s.

Publications and helpful links

General Publications

• Hensler M, Rakova J, Kasikova L, Lanickova T, Pasulka J, Holicek P, Hraska M, Hrnciarova T, Kadlecova P, Schoenenberger A, Sochorova K, Rozkova D, Sojka L, Drozenova J, Laco J, Horvath R, Podrazil M, Hongyan G, Brtnicky T, Halaska MJ, Rob L, Ryska A, Coosemans A, Vergote I, Garg AD, Cibula D, Bartunkova J, Spisek R, Fucikova J. Peripheral gene signatures reveal distinct cancer patient immunotypes with therapeutic implications for autologous DC-based vaccines. Oncoimmunology. 2022 Jul 22;11(1):2101596. doi: 10.1080/2162402X.2022.2101596. eCollection 2022.
• Palata O, Podzimkova Hradilova N, Mysikova D, Kutna B, Mrazkova H, Lischke R, Spisek R, Adkins I. Detection of tumor antigens and tumor-antigen specific T cells in NSCLC patients: Correlation of the quality of T cell responses with NSCLC subtype. Immunol Lett. 2020 Mar;219:46-53. doi: 10.1016/j.imlet.2020.01.001. Epub 2020 Jan 10.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2014
• Primary Completion (Actual): January 1, 2018
• Study Completion (Actual): November 1, 2021

Study Registration Dates

• First Submitted: June 3, 2015
• First Submitted That Met QC Criteria: June 9, 2015
• First Posted (Estimate): June 12, 2015

Study Record Updates

• Last Update Posted (Actual): May 4, 2022
• Last Update Submitted That Met QC Criteria: May 3, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Lung Cancer; NSCLC; Vaccine; Immunotherapy; Metastatic; Biological
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms
• Other Study ID Numbers: SLU01; 2014-003084-37 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED