NCT02748889

Brief Summary

This is an open-label study with two parts, a Phase I study and a randomized Phase II study. This study will be conducted at approximately ten sites in the United States. Approximately 178 patients will be enrolled in this trial.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Mar 2016

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 2, 2016

Completed
28 days until next milestone

Study Start

First participant enrolled

March 1, 2016

Completed
2 months until next milestone

First Posted

Study publicly available on registry

April 22, 2016

Completed
1 year until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 9, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 9, 2017

Completed
1.1 years until next milestone

Results Posted

Study results publicly available

July 2, 2018

Completed
Last Updated

July 2, 2018

Status Verified

June 1, 2018

Enrollment Period

1.2 years

First QC Date

February 2, 2016

Results QC Date

April 24, 2018

Last Update Submit

June 29, 2018

Conditions

Small Cell Lung Cancer ( SCLC )

Keywords

SCLCSmall CellLung CancerMPDL3280Aatezolizumab

Outcome Measures

Primary Outcomes (1)

  • Progression Free Survival (PFS) With Carboplatin, Etoposide and MPDL3280A Compared to Chemotherapy Alone According to RECIST v1.1

    Disease progression will be assessed per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT and bone scans.

    From the first occurrence of progression or death, whichever occurred first, assessed up to 2 years.

Study Arms (2)

Carboplatin plus etoposide

ACTIVE COMPARATOR

Carboplatin AUC 5 iv on day 1 every 21 days for 4 cycles Etoposide 100mg/m2 iv on days 1-3 every 21 days for 4 cycles

Drug: CarboplatinDrug: Etoposide

Carboplatin, etoposide and MPDL3280A

EXPERIMENTAL

Carboplatin AUC 5 iv on day 1 every 21 days for 4 cycles Etoposide 100mg/m2 iv on days 1-3 every 21 days for 4 cycles MPDL3280A (Atezolizumab) 1200mg iv on day 1 every 21 days until progression

Drug: CarboplatinDrug: EtoposideBiological: MPDL3280A

Interventions

CarboplatinDRUG

Standard chemotherapy

Also known as: Paraplatin
Carboplatin plus etoposideCarboplatin, etoposide and MPDL3280A
EtoposideDRUG

Standard chemotherapy

Also known as: VP-16, Toposar
Carboplatin plus etoposideCarboplatin, etoposide and MPDL3280A
MPDL3280ABIOLOGICAL

Experimental biologic

Also known as: Atezolizumab
Carboplatin, etoposide and MPDL3280A

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Signed Informed Consent Form (ICF)
  • Ability and willingness to comply with the requirements of the study protocol
  • Age 18 years or older
  • Histological or cytological diagnosis of ES-SCLC (Note: Extensive-stage disease is defined as disease beyond the ipsilateral hemithorax, mediastinum and ipsilateral supraclavicular area and including malignant pleural or pericardial effusion or hematogenous metastases)
  • Patients with mixed histology SCLC and NSCLC are permitted
  • Representative tumor specimens in paraffin blocks (preferred) or at least 10 unstained slides, with an associated pathology report, requested at any time prior to study entry. Tissue from core needle, punch, or excisional biopsy sample collection is preferred but slides from fine needle aspiration, brushing, and lavage samples are acceptable.
  • Adequate hematologic and end organ function, defined by the following laboratory results obtained within 14 days prior to the first study treatment (Cycle 1, Day 1)
  • ANC 1000 cells/mL
  • WBC counts 2500/mL
  • Lymphocyte count 500/mL
  • Platelet count 100,000/mL
  • Hemoglobin 9.0 g/dL (transfusion to meet this criterion is permitted)
  • Serum sodium greater than 120 mmol/L
  • Total bilirubin must be 1.5 ULN with the following exception:
  • Patients with known Gilbert disease who have serum bilirubin level 3 ULN may be enrolled.
  • +11 more criteria

You may not qualify if:

  • Inability to comply with study and follow-up procedures
  • Limited stage SCLC appropriate for definitive treatment with chemoradiation
  • Prior systemic anti-cancer therapy for small cell lung cancer
  • Prior palliative radiation therapy less than 2 weeks prior to administration of study treatment or prior whole brain radiation therapy (WBRT) less than 4 weeks prior to study treatment
  • Symptomatic brain metastases (patients with asymptomatic brain metastases may be eligible provided other criteria are met)
  • Leptomeningeal disease or carcinomatous meningitis
  • Uncontrolled hypercalcemia ( ≥1.5 mmol/L ionized calcium or Ca \> 12 mg/dL) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab (patients receiving bisphosphonate therapy or denosumab to prevent skeletal events and who do not have a history of clinically significant hypercalcemia are eligible, though patients receiving denosumab must be willing and eligible to receive bisphosphonates instead)
  • Malignancies other than SCLC within 2 years prior to administration of study treatment with the exception of those with a negligible risk of metastases or death treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix or breast, basal or squamous cell skin cancer, or localized prostate cancer treated definitively)
  • Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis, fatty liver, and inherited liver disease
  • Pregnancy, lactation, or breastfeeding
  • History or risk of autoimmune disease, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Bell's palsy, Guillain-Barré syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis
  • Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone may be eligible.
  • Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen may be eligible.
  • Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions:
  • Patients with psoriasis must have a baseline ophthalmologic exam to rule out ocular manifestations
  • +27 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Georgetown Lombardi Comprehensive Cancer Center

Washington D.C., District of Columbia, 20007, United States

Location

Related Publications (11)

  • Rossi A, Di Maio M, Chiodini P, Rudd RM, Okamoto H, Skarlos DV, Fruh M, Qian W, Tamura T, Samantas E, Shibata T, Perrone F, Gallo C, Gridelli C, Martelli O, Lee SM. Carboplatin- or cisplatin-based chemotherapy in first-line treatment of small-cell lung cancer: the COCIS meta-analysis of individual patient data. J Clin Oncol. 2012 May 10;30(14):1692-8. doi: 10.1200/JCO.2011.40.4905. Epub 2012 Apr 2.

    PMID: 22473169BACKGROUND

  • Blank C, Gajewski TF, Mackensen A. Interaction of PD-L1 on tumor cells with PD-1 on tumor-specific T cells as a mechanism of immune evasion: implications for tumor immunotherapy. Cancer Immunol Immunother. 2005 Apr;54(4):307-14. doi: 10.1007/s00262-004-0593-x. Epub 2004 Dec 15.

    PMID: 15599732BACKGROUND

  • Blank C, Mackensen A. Contribution of the PD-L1/PD-1 pathway to T-cell exhaustion: an update on implications for chronic infections and tumor evasion. Cancer Immunol Immunother. 2007 May;56(5):739-45. doi: 10.1007/s00262-006-0272-1. Epub 2006 Dec 29.

    PMID: 17195077BACKGROUND

  • Brahmer J, Reckamp KL, Baas P, Crino L, Eberhardt WE, Poddubskaya E, Antonia S, Pluzanski A, Vokes EE, Holgado E, Waterhouse D, Ready N, Gainor J, Aren Frontera O, Havel L, Steins M, Garassino MC, Aerts JG, Domine M, Paz-Ares L, Reck M, Baudelet C, Harbison CT, Lestini B, Spigel DR. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. N Engl J Med. 2015 Jul 9;373(2):123-35. doi: 10.1056/NEJMoa1504627. Epub 2015 May 31.

    PMID: 26028407BACKGROUND

  • Segal, N.H., et al., Preliminary data from a multi-arm expansion study of MEDI4736, an anti-PD-L1 antibody. J Clin Oncol, 2014. 32(5S): p. abstr 3002

    BACKGROUND

  • Lutzky, J., et al., A phase 1 study of MEDI4736, an anti-PD-L1 antibody, in patients with advanced solid tumors. J Clin Oncol, 2014. 32(5S): p. abstr 3001

    BACKGROUND

  • Antonia, S.J., et al., Phase I/II study of nivolumab with or without ipilimumab for treatment of recurrent small cell lung cancer (SCLC): CA209-032. J Clin Oncol, 2015. 33: p. abstr 7503

    BACKGROUND

  • Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, Drake CG, Camacho LH, Kauh J, Odunsi K, Pitot HC, Hamid O, Bhatia S, Martins R, Eaton K, Chen S, Salay TM, Alaparthy S, Grosso JF, Korman AJ, Parker SM, Agrawal S, Goldberg SM, Pardoll DM, Gupta A, Wigginton JM. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012 Jun 28;366(26):2455-65. doi: 10.1056/NEJMoa1200694. Epub 2012 Jun 2.

    PMID: 22658128BACKGROUND

  • Reck M, Bondarenko I, Luft A, Serwatowski P, Barlesi F, Chacko R, Sebastian M, Lu H, Cuillerot JM, Lynch TJ. Ipilimumab in combination with paclitaxel and carboplatin as first-line therapy in extensive-disease-small-cell lung cancer: results from a randomized, double-blind, multicenter phase 2 trial. Ann Oncol. 2013 Jan;24(1):75-83. doi: 10.1093/annonc/mds213. Epub 2012 Aug 2.

    PMID: 22858559BACKGROUND

  • Liu, S.V., et al., Safety and efficacy of MPDL3280A (anti-PDL1) in combination with platinum-based doublet chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). J Clin Oncol, 2015. 33: p. abstr 8030

    BACKGROUND

  • Powderly, J.D., et al., Biomarkers and associations with the clinical activity of PD-L1 blockade in a MPDL3280A study. J Clin Oncol, 2013. suppl; abstr 3001

    BACKGROUND

MeSH Terms

Conditions

Small Cell Lung CarcinomaLung Neoplasms

Interventions

CarboplatinEtoposideatezolizumab

Condition Hierarchy (Ancestors)

Carcinoma, BronchogenicBronchial NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsNeoplasms by SiteNeoplasmsLung DiseasesRespiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Coordination ComplexesOrganic ChemicalsPodophyllotoxinTetrahydronaphthalenesNaphthalenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsPolycyclic CompoundsGlucosidesGlycosidesCarbohydrates

Results Point of Contact

Title
Dr Giuseppe Giaccone
Organization
Georgetown University Medical Center - Lombardi Comprehensive Cancer Center
gg496@georgetown.edu
202-687-7072

Study Officials

  • Giuseppe ( Beppe) Giaccone, Md,PhD

    Georgetown Lombardi Comprehensive Cancer Center

    STUDY CHAIR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Associate Director for Clinical Research

Study Record Dates

First Submitted

February 2, 2016

First Posted

April 22, 2016

Study Start

March 1, 2016

Primary Completion

May 9, 2017

Study Completion

May 9, 2017

Last Updated

July 2, 2018

Results First Posted

July 2, 2018

Record last verified: 2018-06

Data Sharing

IPD Sharing
Will not share

Locations

US(1)