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
Overview
- Phase
- Phase 1
- Intervention
- CC-90011
- Conditions
- Small Cell Lung Carcinoma
- Sponsor
- Celgene
- Enrollment
- 90
- Locations
- 13
- Primary Endpoint
- Dose-Limiting Toxicity (DLT)
- Status
- Completed
- Last Updated
- last year
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male and female subject is 18 years of age or older at the time of signing the informed consent form (ICF).
- •Subject with histological or cytological confirmation of extensive stage SCLC according to 2015 WHO classification (Travis, 2015).
- •Subject must be able to provide fresh or archival tumor tissues
- •Subject is found suitable for at least 4 cycles of platinum-based standard chemotherapy.
- •Subject has at least 1 site of measurable disease per RECIST 1.
- •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
Exclusion Criteria
- •Subject has received anticancer therapy (either approved or investigational, including radiation with curative intent) for SCLC prior to study entry.
- •Subject has undergone major surgery ≤ 4 weeks prior to Cycle 1 Day 1 or has not recovered from surgery.
- •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-
- •Subject with symptomatic or uncontrolled ulcers (gastric or duodenal), particularly those with a history of and/or risk of perforation and GI tract hemorrhages.
- •Subject with any hemorrhage/bleeding event \> CTCAE Grade 2 or hemoptysis \> 1 teaspoon within 4 weeks prior to the first dose.
- •Subject with symptomatic and untreated or unstable central nervous system (CNS) metastases.
- •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.
Arms & Interventions
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.
Intervention: CC-90011
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.
Intervention: Cisplatin
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
Intervention: Carboplatin
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
Intervention: Etoposide
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 IV 240 mg Day 1 of each chemotherapy cycle, will be explored. For CC-90011 in combination with chemotherapy and nivolumab, the starting dose will be the RP2D of CC-90011 in combination with chemotherapy. A maintenance therapy will be given to subjects responding to the combination of CC-90011 with chemotherapy or to chemotherapy with nivolumab, as per RECIST 1.1. These subjects will receive 60 mg or 40 mg (in case of combination with nivolumab) of CC-90011 orally once weekly on Days 1, 8, 15, and 22, during cycles of 28-day each and, in the case of the combination with nivolumab, nivolumab IV 480 mg on Day 1 during cycles of 28-day each.
Intervention: Nivolumab
Outcomes
Primary Outcomes
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
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
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 Outcomes
- Pharmacokinetics- t1/2(Up to approximately 2 years)
- Pharmacokinetics- AUC(Up to approximately 2 years)
- Pharmacokinetics- Cmax(Up to approximately 2 years)
- Objective Response Rate (ORR)(Up to approximately 2 years)
- Pharmacokinetics- Tmax(Up to approximately 2 years)
- Progression-free Survival (PFS)(Up to approximately 2 years)
- Overall Survival (OS)(Up to approximately 2 years)
- Pharmacokinetics- CL/F(Up to approximately 2 years)
- Pharmacokinetics- VzF(Up to approximately 2 years)