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Combination of Atezolizumab With Dendritic Cell Vaccine in Patients With Lung Cancer (VENEZO-LUNG)

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: NCT04487756
Recruitment Status : Recruiting
First Posted : July 27, 2020
Last Update Posted : July 7, 2021
Sponsor:
Collaborators:
Roche Pharma AG
Fundacion Clinic per a la Recerca Biomédica
Information provided by (Responsible Party):
Instituto Oncológico Dr Rosell

Brief Summary:

This is a single-arm Phase Ib/II multicenter open-label study, with translational sub-study, of atezolizumab plus autologous dendritic cell vaccine as maintenance treatment in extensive-stage small cell lung cancer (ES-SCLC). It is expected that three Spanish sites will include patients in this study.

Patients will receive standard treatment with carboplatin and etoposide, plus atezolizumab for four 21-day cycles (induction phase), followed by a maintenance phase during which they will receive the dendritic cell vaccine (6 doses maximum) in combination with atezolizumab until they had unacceptable toxic effects, disease progression according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, or no additional clinical benefit.

The two primary endpoints are the investigator-assessed toxicity and the 6 months PFS, both in the intention-to-treat population. Secondary Outcome Measures include: Duration of clinical benefit (DCB), Overall survival (OS) and Overall response rate (ORR)

The translational substudy will include:

Analysis of tumor tissue samples will consist of PD-L1 Immunohistochemistry testing, RNA expression, Work Environmental Scale (WES) analysis, and flow cytometry in pretreatment fresh tumor tissue.

The analysis will consist of T cell immunophenotyping, DC immunophenotyping, Tumoral RNA analysis by nanostring and tumoral cell-free DNA analysis by WES and cytokine analysis


Condition or disease Intervention/treatment Phase
Extensive-stage Small Cell Lung Cancer Drug: Atezolizumab 1200 mg in 20 ML Injection Biological: ADC Vaccine Drug: Carboplatin Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: single arm Phase Ib/II multicenter open label study, with translational sub-study
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase Ib/II Trial of the Combination of Atezolizumab With Dendritic Cell Vaccination as Maintenance Treatment in Patients With Extensive Stage Small Cell Lung Cancer (ES-SCLC) After Induction Treatment
Actual Study Start Date : March 17, 2021
Estimated Primary Completion Date : October 2021
Estimated Study Completion Date : October 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Atezo+DCvac

- Induction (4 cycles, every 3 weeks): Carboplatin area under the curve (AUC) 5 (5 mg per milliliter per minute, administered intravenously on day 1 of each cycle) and etoposide (100 mg per square meter of body-surface area, administered intravenously on days 1 through 3 of each cycle) Atezolizumab, 1200 mg administered intravenously every 3 weeks on day 1 of each cycle)

- Maintenance (only patients without PD after 4 induction cycles, up to PD): Atezolizumab iv (1200 mg/IV on day 1 every 3 weeks) DCV intradermally (max. 6 doses) on weeks 1, 3, 6, 9, 21, 33.

Drug: Atezolizumab 1200 mg in 20 ML Injection

- Induction (4 cycles, every 3 weeks): Atezolizumab, 1200 mg administered intravenously every 3 weeks on day 1 of each cycle)

- Maintenance (only patients without PD after 4 induction cycles, up to PD): Atezolizumab iv (1200 mg/IV on day 1 every 3 weeks)

Other Name: Tecentriq

Biological: ADC Vaccine
- Maintenance (only patients without PD after 4 induction cycles, up to PD): DCV intradermally (max. 6 doses) on weeks 1, 3, 6, 9, 21, 33.
Other Name: Autologous Dendritic cell (ADC) vaccine, Dendritic cell (DC) vaccine

Drug: Carboplatin
- Induction (4 cycles, every 3 weeks): Carboplatin AUC 5 (5 mg per milliliter per minute, administered intravenously on day 1 of each cycle) and etoposide (100 mg per square meter of body-surface area, administered intravenously on days 1 through 3 of each cycle)
Other Name: Carboplatino (Teva/Accord/Pharmacia)




Primary Outcome Measures :
  1. Progression-Free Survival (PFS) rate at 6 months [ Time Frame: At 6 months after start of treatment ]
    Calculated as the percentage of participants alive and without disease progression, as assessed by the Investigator using RECIST v1.1

  2. Frequency and severity of AEs and SAEs (Safety) [ Time Frame: Throughout the study. Approximately 3 years ]
    he number of patients with AEs and SAEs, changes in laboratory values, vital signs, ECGs, and results of physician examinations graded according to the CTCAE v 5.0.


Secondary Outcome Measures :
  1. Duration of clinical benefit (DCB) as per RECIST 1.1 [ Time Frame: Throughout the study. Approximately 3 years ]
    DCB calculated as the time (in months) from first dose of treatment to progression (or death from any cause) in patients who had a best overall response of CR, PR, or SD of ≥ 24 weeks.

  2. Overall Survival (OS) [ Time Frame: Throughout the study. Approximately 3 years ]
    Median Overall Survival (mOS) is calculated as the time from date of inclusion to date of death due to any cause.

  3. Objective response rate (ORR1) as per RECIST 1.1 [ Time Frame: Throughout the study. Approximately 3 years ]
    Rate of patients that achieve partial or complete response as best response during study induction treatment

  4. Objective response rate (ORR2) as per RECIST 1.1 [ Time Frame: Throughout the study. Approximately 3 years ]
    Rate of patients that have a further best response during maintenance treatment



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. Histological diagnosis of extensive-stage small cell lung cancer (ES-SCLC). Unequivocally confirmed diagnosis of SCLC by histology preferably including the presence of neuroendocrine features by immunohistochemistry.
  2. Centrally confirmed tumor tissue viability for vaccine preparation.
  3. No previous cancer treatment for advanced disease
  4. Life expectancy at least 16 weeks
  5. ECOG performance status 0 or 1.
  6. Adequate normal organ and marrow function as defined below:

    Absolute neutrophil count ≥ 1.5 x 109 cells/L Platelets ≥ 100 x 109/L Hemoglobin ≥ 9 g/dL Aspartate and alanine aminotransferases (AST, ALT) ≤ 2.5 x upper limit of normal (ULN) (≤ 5 x ULN, if documented liver metastases are present) Total bilirubin ≤ 2 x ULN (except patients with documented Gilbert's syndrome) Creatinine < 2 mg/dl (or a glomerular filtration rate > 60)

  7. Prior palliative radiotherapy must have been completed at least 2 weeks prior to start the study treatment (subjects may receive localized palliative radiotherapy while receiving study drug).
  8. Subjects with brain metastases are eligible if they are asymptomatic, are treated, or are neurological stable for at least 2 weeks without the use of steroids, or on a stable or decreasing dose of < 10 mg daily prednisone or equivalent.
  9. Must be willing and able to accept one leukapheresis procedures
  10. Written informed consent of approved by the investigator's Institutional Review Board (IRB)/Independent Ethics Committee (IEC), prior to the performance of any trial activities.
  11. Male or female subjects aged ≥ 18 years.
  12. Measurable disease by RECIST.1.1 criteria.
  13. Highly effective contraception for both male and female subjects throughout the study and for at least 30 days after the last atezolizumab treatment administration if the risk of conception exists.
  14. Negative serum pregnancy test at screening for women of childbearing potential. Female subjects must either be of non-reproductive potential (ie, post-menopausal by history: ≥60 years old and no menses for ≥1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry.
  15. Central negative serologic determination to HBsAg, Anti-HBc, HBV, HCV, HCV RNA, HIV-I RNA, Agp24 IIIV + AC IIIV ½ (MLIA) serum, IgG antigen core v. hepatitis B, RPR (Ac reaginic Lues-RPR, serum), Ac anti-HTLV I/II (if the patient came from an endemic zone), Ac anti-Trypanosoma Cruzi, Chagas, (if a patient came from the endemic zone), when RPR positive or doubtful for confirmation: IgG T. pallidum (ELISA) immunoglobulin M (IgM) T. pallidum (ELISA), when IgG T. Pallidum doubtful: Pt confirmatory immunoglobulin G (IgG)/IGM, T pallidum (LIA).

Exclusion Criteria:

  1. Prior chemotherapy for extensive-stage ES-SCLC
  2. Any prior anti-PD-1/PD-L1 antibody therapy
  3. History of, or significant evidence of risk for, severe chronic inflammatory or autoimmune disease
  4. Potential requirement for systemic corticosteroids or concurrent immunosuppressive drugs based on prior history or received systemic steroids within the last 2 weeks prior to enrollment (inhaled or topical steroids at standard doses are allowed)
  5. Human immunodeficiency virus (HIV) seropositivity, active Hepatitis B or C seropositivity
  6. Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol
  7. Pregnancy or breastfeeding; female patients must be surgically sterile or be postmenopausal for two years or must agree to use effective contraception during the period of treatment and 6 months after; all female patients with reproductive potential must have a negative pregnancy test (serum/urine) within 24 hours from starting the conditioning chemotherapy; the definition of effective contraception will be based on the judgment of the study investigators; patients who are breastfeeding are not allowed on study
  8. Any unresolved toxicity (CTCAE grade 2) from previous anti-cancer therapy. Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included (e.g., hearing loss, peripheral neuropathy).
  9. Active or prior documented autoimmune disease within the past 2 years NOTE: Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded. For phase I cohort, patients with autoimmune paraneoplastic syndromes will be also excluded.
  10. Any syndrome that requires systemic corticosteroid/immunosuppressive medication EXCEPT for syndromes which would not be expected to recur in the absence of an external trigger (vitiligo, autoimmune thyroiditis, or type 1 diabetes mellitus are permitted to enroll)
  11. Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).
  12. History of primary immunodeficiency.
  13. History of allogeneic organ transplant. 14 History of hypersensitivity to atezolizumab / ADC vaccine or any excipient.

15- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diathesis including any subject known to have evidence of acute or chronic hepatitis B or C or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent.

16- Known history of active tuberculosis. 17- Subjects with previous malignancies (except for non-melanoma skin cancer, and cancer in situ of the bladder, gastric, colon, cervical/dysplasia, melanoma, breast) are excluded unless a complete remission was achieved at least 5 years prior to study entry and no additional therapy is required or anticipated to be required during the study period.

18- Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving atezolizumab.

19- Prior allogeneic stem-cell transplantation. 20- Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥ 3 NCI-CTCAE v 5.0), any history of anaphylaxis, or uncontrolled asthma.

21- Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ highly effective birth control from screening to 180 days after the last dose of ADC + atezolizumab combination therapy.


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): NCT04487756


Contacts
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Contact: Federico Nepote 93 434 44 12 investigacion@mfar.net
Contact: Verónica Roca 93 434 44 12 investigacion@mfar.net

Locations
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Spain
ICO Badalona Recruiting
Badalona, Barcelona, Spain, 08916
Contact: Principal Investigator Selected by Sponsor, M.D., Ph.D.       investigacion@mfar.net   
Principal Investigator: Principal Investigator Selected by Sponsor         
Quirón Dexeus Recruiting
Barcelona, Spain, 08028
Contact: Investigator Selected by Sponsor, M.D., Ph.D.       investigacion@mfar.net   
Principal Investigator: investigator Selected by Sponsor, M.D., Ph.D.         
Hospital Clínic Barcelona Recruiting
Barcelona, Spain, 08036
Contact: Investigator Selected by Sponsor, M.D.       investigacion@mfar.net   
Principal Investigator: Investigator Selected by Sponsor, M.D.         
Sponsors and Collaborators
Instituto Oncológico Dr Rosell
Roche Pharma AG
Fundacion Clinic per a la Recerca Biomédica
Investigators
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Study Chair: María González Cao Hospital Quirón-Dexeus
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Responsible Party: Instituto Oncológico Dr Rosell
ClinicalTrials.gov Identifier: NCT04487756    
Other Study ID Numbers: IOR-IISML42037
2020-000448-72 ( EudraCT Number )
First Posted: July 27, 2020    Key Record Dates
Last Update Posted: July 7, 2021
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Instituto Oncológico Dr Rosell:
Small cell lung cancer
Atezolizumab
Dendritic cell vaccine
Safety
Efficacy
Additional relevant MeSH terms:
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Lung Neoplasms
Small Cell Lung Carcinoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Carboplatin
Atezolizumab
Vaccines
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents