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A Safety, Tolerability and Preliminary Efficacy Evaluation of CC-90011 Given in Combination With Cisplatin and Etoposide in Subjects With First Line, Extensive Stage Small Cell Lung Cancer

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: NCT03850067
Recruitment Status : Recruiting
First Posted : February 21, 2019
Last Update Posted : August 31, 2020
Sponsor:
Information provided by (Responsible Party):
Celgene

Brief Summary:

CC-90011-SCLC-001 is a multicenter, Phase 1b, open-label, dose finding study to assess the safety, tolerability, and preliminary efficacy of CC-90011 given concurrently and sequentially to standard of care platinum-based, cisplatin and etoposide, carboplatin and etoposide and/or etoposide and Nivolumab to subjects with first line ES SCLC.

The dose finding part of the study will explore escalating oral doses of CC-90011 in combination with cisplatin, etoposide and/or carboplatin with or without Nivolumab (chemotherapy), to determine the maximum tolerated dose of CC- 90011 in combination with chemotherapy with or without Nivolumab to subjects with first line ES SCLC.


Condition or disease Intervention/treatment Phase
Small Cell Lung Carcinoma Drug: CC-90011 Drug: Cisplatin Drug: Carboplatin Drug: Etoposide Drug: Nivolumab Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b, Multicenter, Open-label, Dose Finding Study to Assess the Safety, Tolerability, and Preliminary Efficacy of CC-90011 Given in Combination With Cisplatin and Etoposide in First -Line, Extensive Stage Subjects With Small Cell Lung Cancer
Actual Study Start Date : March 12, 2019
Estimated Primary Completion Date : September 30, 2021
Estimated Study Completion Date : December 30, 2022


Arm Intervention/treatment
Experimental: CC-90011 in combination with Cisplatin and Etoposide
During the Chemotherapy Treatment Period, the dose escalation is designed to explore three dose levels of CC-90011, for example 20, 40, and 60 mg as determined by Bayesian design, administered orally Days 1 and 8, in combination with cisplatin intravenous (IV) 75 mg/m2, Day 1, and etoposide iv 100 mg/m2 on Days 1, 2, and 3, for 4 cycles of 21 days each. Subjects completing the chemotherapy and being responders as per RECIST 1.1 will enter the Maintenance Treatment Period. Subjects completing 6 cycles of maintenance treatment subject will be treated only with CC-90011 at RP2D (60 mg) and continuing on CC-90011 are only required to have clinic visits/assessments performed on Day 1 (± 3 days) of each subsequent cycle (Cycles 6 and higher) unless more frequent visits are clinically indicated.
Drug: CC-90011
CC-90011

Drug: Cisplatin
Cisplatin

Experimental: CC-90011 in combination with Carboplatin and Etoposide
During the Chemotherapy Treatment Period, the dose escalation is designed to explore three dose levels of CC-90011, for example 20, 40, and 60 mg as determined by Bayesian design, administered orally Days 1 and 8, in combination with cisplatin intravenous (IV) 75 mg/m2, Day 1, and etoposide iv 100 mg/m2 on Days 1, 2, and 3, for 4 cycles of 21 days each. Subjects completing the chemotherapy and being responders as per RECIST 1.1 will enter the Maintenance Treatment Period. Subjects completing 6 cycles of maintenance treatment subject will be treated only with CC-90011 at RP2D (60 mg) and continuing on CC-90011 are only required to have clinic visits/assessments performed on Day 1 (± 3 days) of each subsequent cycle (Cycles 6 and higher) unless more frequent visits are clinically indicated
Drug: Carboplatin
Carboplatin

Drug: Etoposide
Etoposide

Experimental: Nivolumab combination
When the RP2D of CC-90011 in combination with cisplatin or carboplatin and etoposide is determined, the combination of CC-90011 at RP2D with cisplatin or carboplatin and etoposide plus nivolumab (Nivo) IV 240 mg Day 1 of each chemotherapy cycle, will be explored. For CC-90011 in combination with chemotherapy and Nivo, the starting dose will be the RP2D of CC-90011 in combination with chemotherapy. For subjects responding to the initial combination of CC-90011 and chemotherapy, as per RECIST 1.1, CC-90011 single agent will be given as maintenance therapy. These subjects will receive 60 mg of CC-90011 orally once weekly, Days 1, 8, 15, and 22, during cycles of 28 days each. For subjects responding to the initial combination of CC-90011 and chemotherapy with Nivo, CC-90011 with Nivo will be given as maintenance therapy. These subjects will receive 60 mg of CC-90011 orally once weekly, Days 1, 8, 15, and 22, and Nivo IV 240 mg Days 1 and 15 during cycles of 28 days each
Drug: Nivolumab
Nivolumab




Primary Outcome Measures :
  1. Dose-Limiting Toxicity (DLT) [ Time Frame: Up to approximately 2 years ]
    A DLT is defined as any of the toxicities described in the protocol occurring within the DLT assessment unless the event can clearly be determined to be unrelated to CC-90011

  2. Maximum Tolerated Dose (MTD) [ Time Frame: Up to approximately 2 years ]
    MTD is the highest dose that causes DLTs in not more than 33% of the subjects treated with CC-90010 in the first cycle with at least 6 evaluable subjects treated at this dose

  3. Adverse Events (AEs) [ Time Frame: Up to approximately 3 years ]
    An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values, regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) should be considered an AE


Secondary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: Up to approximately 2 years ]
    Is defined as the percent of subjects whose best response is complete response (CR) or partial response (PR).

  2. Progression-free Survival (PFS) [ Time Frame: Up to approximately 2 years ]
    Is defined as the time from the first dose of study drug to the first occurrence of disease progression or death from any cause.

  3. Overall Survival (OS) [ Time Frame: Up to approximately 2 years ]
    Is measured as the time from the first dose of CC-90011 to death due to any cause.

  4. Pharmacokinetics- Cmax [ Time Frame: Up to approximately 2 years ]
    Maximum observed plasma concentration

  5. Pharmacokinetics- AUC [ Time Frame: Up to approximately 2 years ]
    Area under the plasma concentration time-curve

  6. Pharmacokinetics- Tmax [ Time Frame: Up to approximately 2 years ]
    Time to maximum plasma concentration

  7. Pharmacokinetics- t1/2 [ Time Frame: Up to approximately 2 years ]
    Terminal half-life

  8. Pharmacokinetics- CL/F [ Time Frame: Up to approximately 2 years ]
    Apparent clearance

  9. Pharmacokinetics- VzF [ Time Frame: Up to approximately 2 years ]
    Apparent volume of distribution



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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 and female subject is 18 years of age or older at the time of signing the informed consent form (ICF).
  2. Subject with histological or cytological confirmation of extensive stage SCLC according to 2015 WHO classification (Travis, 2015).
  3. Subject must be able to provide fresh or archival tumor tissues
  4. Subject is found suitable for at least 4 cycles of platinum-based standard chemotherapy.
  5. Subject has at least 1 site of measurable disease per RECIST 1.1.
  6. Subject must have the following laboratory values:

    • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
    • Hemoglobin (Hgb) ≥ 10 g/dL (≥ 100 g/L or > 6.2 mmol/L)
    • Platelet count (Plt) ≥ 150 x 109/L
    • Serum aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase/serum glutamate pyruvate transaminase (ALT/SGPT) ≤ 3.0 x upper limit of normal (ULN) or ≤ 5.0 x ULN if liver metastases are present
    • Serum total bilirubin ≤ 1.5 x ULN
    • Serum albumin ≥ 3.0 g/dL
    • Serum creatinine ≤ 1.5 mg/dL or creatinine clearance ≥ 60 mL/min (see Appendix G to see creatinine clearance formula). For the purposes of this protocol, the glomerular filtration rate (GFR) is considered to be equivalent to the creatinine clearance.
    • Prothrombin time (or international normalized ratio [INR]) and activated partial thromboplastin time (APTT) ≤ 1.5 ULN

Exclusion Criteria:

  1. Subject has received anticancer therapy (either approved or investigational, including radiation with curative intent) for SCLC prior to study entry.
  2. Subject has undergone major surgery ≤ 4 weeks prior to Cycle 1 Day 1 or has not recovered from surgery.
  3. Subject has persistent diarrhea due to a malabsorptive syndrome (such as celiac sprue or inflammatory bowel disease) ≥ NCI CTCAE Grade 2, despite medical management), or any other significant gastrointestinal (GI) disorder that could affect the absorption of CC- 90011.
  4. Subject with symptomatic or uncontrolled ulcers (gastric or duodenal), particularly those with a history of and/or risk of perforation and GI tract hemorrhages.
  5. Subject with any hemorrhage/bleeding event > CTCAE Grade 2 or hemoptysis > 1 teaspoon within 4 weeks prior to the first dose.
  6. Subject with symptomatic and untreated or unstable central nervous system (CNS) metastases.
  7. Subject has impaired cardiac function or clinically significant cardiac diseases, including any of the following:

    • Left ventricular ejection fraction (LVEF) < 45% as determined by multigated acquisition (MUGA) scan or echocardiogram (ECHO).
    • Complete left bundle branch or bifascicular block.
    • Congenital long QT syndrome.
    • Persistent or clinically meaningful ventricular arrhythmias or atrial fibrillation.
    • QTcF ≥ 480 msec on Screening ECG (mean of triplicate recordings).
  8. Subject has other clinically significant heart disease such as congestive heart failure requiring treatment or uncontrolled hypertension (blood pressure ≥ 160/95 mm Hg).
  9. Subject is a pregnant or nursing female.
  10. Subject has known human immunodeficiency virus (HIV) infection.
  11. Subject has known chronic active hepatitis B or C virus (HBV, HCV) infection.
  12. Subject with ongoing treatment with chronic, therapeutic dosing of anticoagulants (eg, warfarin, low molecular weight heparin, Factor Xa inhibitors, thrombin antagonist).
  13. Subject has a history of concurrent second cancers requiring active, ongoing systemic treatment.
  14. Subject has Grade 2 peripheral sensory neuropathy.
  15. Subject with poor bone marrow reserve as assessed by Investigator.
  16. Subject has any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
  17. Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
  18. Subject has any condition that confounds the ability to interpret data from the study.

    For the subjects treated with nivolumab:

  19. Subject has received prior therapies targeting PD-1 or PD-L1
  20. Subject has a history of persistent skin rash ≥ NCI CTCAE Grade 2.
  21. Subject with an autoimmune disease, or any other condition, requiring systemic treatment with either corticosteroids within 14 days (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 30 days of enrollment. Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.

    • Subjects with type 1 diabetes mellitus, hypothyroidism only requiring hormone replacement, disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.

  22. Subject has received treatment with botanical preparations (eg, herbal supplements or traditional Chinese medicines) to treat the disease under study within 2 weeks prior to randomization. Refer to Section 8.2 for prohibited therapies.
  23. Subject has history of allergy or hypersensitivity to study drug components.
  24. Subject has received a live/attenuated vaccine within 30 days of first treatment.

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): NCT03850067


Contacts
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Contact: Associate Director Clinical Trial Disclosure 1-888-260-1599 clinicaltrialdisclosure@celgene.com

Locations
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France
Hospital Le Timone Active, not recruiting
Marseille Cedex 5, France, 13385
CHU Nantes Hopital Nord Laennec Active, not recruiting
Saint-Herblain, France, 44800
Gustave Roussy Active, not recruiting
Villejuif CEDEX, France, 94805
Italy
Azienda Ospedaliero Universitaria Ospedali Riuniti "Umberto I, G.M. Lancisi, G. Salesi" Recruiting
Ancona, Italy, 60126
Polyclinic S. Orsola-Malpighi Recruiting
Bologna, Italy, 40138
Istituto Clinico Humanitas Recruiting
Rozzano (MI), Italy, 20089
Spain
Vall d´Hebron University Hospital Recruiting
Barcelona, Spain, 08035
Hospital Universitario Germans Trias i Pujol Recruiting
Barcelona, Spain, 08916
Hospital Doce de Octubre Recruiting
Madrid, Spain, 28041
Hospital Universitario Puerta de Hierro Recruiting
Majadahonda, Madrid, Spain, 28222
Hospital Universitario Virgen de la Victoria Recruiting
Malaga, Spain, 29010
Hospital Clinico Universitario de Valencia Recruiting
Valencia, Spain, 46010
Hospital Universitario La Fe Recruiting
Valencia, Spain, 46026
Sponsors and Collaborators
Celgene
Investigators
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Study Director: Zariana Nikolova, MD, PHD Celgene Corporation
Principal Investigator: Oscar Juan Vidal, MD, PhD Hospital Universitario La Fe
Principal Investigator: Stefania Salvagni, MD Azienda Ospedaliero Universitarua, Policlinico S. Orsola Malpighi
Principal Investigator: Rossana Berardi, MD Ospedali Riuniti di Ancona
Principal Investigator: Armando Santoro, MD IRCCS Instituto Clinic Humanitas
Principal Investigator: Benjamin Besse, MD, PhD Gustave Roussy, Ditep
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT03850067    
Other Study ID Numbers: CC-90011-SCLC-001
U1111-1228-2067 ( Registry Identifier: WHO )
2018-002799-42 ( EudraCT Number )
First Posted: February 21, 2019    Key Record Dates
Last Update Posted: August 31, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Information relating to our policy on data sharing and the process for requesting data can be found at the following link:

https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/

Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: See Plan Description
Access Criteria: See Plan Description
URL: https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/

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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 Celgene:
Safety
CC-90011
Extensive stage small cell lung cancer
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
Etoposide
Nivolumab
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological