February 21, 2019
March 2, 2021
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.
|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.
|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
|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
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
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
- 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
- Prothrombin time (or international normalized ratio [INR]) and activated partial
thromboplastin time (APTT) ≤ 1.5 ULN
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)
7. Subject has impaired cardiac function or clinically significant cardiac diseases,
including any of the following:
- Left ventricular ejection fraction (LVEF) 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.
Contact: Associate Director Clinical Trial Disclosure 1-888-260-1599 email@example.com
Hospital Le Timone
Marseille Cedex 5
CHU Nantes Hopital Nord Laennec
Azienda Ospedaliero Universitaria Ospedali Riuniti "Umberto I, G.M. Lancisi, G. Salesi"
Polyclinic S. Orsola-Malpighi
Istituto Clinico Humanitas
Vall d´Hebron University Hospital
Hospital Universitario Germans Trias i Pujol
Hospital Doce de Octubre
Hospital Universitario Puerta de Hierro
Hospital Universitario Virgen de la Victoria
Hospital Clinico Universitario de Valencia
Hospital Universitario La Fe
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
Kanouni T, Severin C, Cho RW, Yuen NY, Xu J, Shi L, Lai C, Del Rosario JR, Stansfield RK, Lawton LN, Hosfield D, O'Connell S, Kreilein MM, Tavares-Greco P, Nie Z, Kaldor SW, Veal JM, Stafford JA, Chen YK. Discovery of CC-90011: A Potent and Selective Reversible Inhibitor of Lysine Specific Demethylase 1 (LSD1). J Med Chem. 2020 Dec 10;63(23):14522-14529. doi: 10.1021/acs.jmedchem.0c00978. Epub 2020 Oct 9.