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A Safety and Efficacy Study of CC-90011 in Subjects With Relapsed and/or Refractory Solid Tumors and Non-Hodgkin's Lymphomas

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ClinicalTrials.gov Identifier: NCT02875223
Recruitment Status : Recruiting
First Posted : August 23, 2016
Last Update Posted : July 30, 2021
Sponsor:
Information provided by (Responsible Party):
Celgene

Tracking Information
First Submitted Date  ICMJE August 18, 2016
First Posted Date  ICMJE August 23, 2016
Last Update Posted Date July 30, 2021
Actual Study Start Date  ICMJE August 31, 2016
Estimated Primary Completion Date September 12, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 28, 2018)
  • Dose-Limiting Toxicity (DLT) [ Time Frame: Up to approximately 28 days ]
    Number of participants with DLT
  • Adverse Events (AEs) [ Time Frame: Up to 6 years ]
    Number of participants with adverse events
Original Primary Outcome Measures  ICMJE
 (submitted: August 18, 2016)
  • Dose-Limiting Toxicity (DLT) [ Time Frame: Up to approximately 28 days ]
    Number of participants with DLT
  • Adverse Events (AEs) [ Time Frame: Up to 5 years ]
    Number of participants with adverse events
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 8, 2021)
  • Clinical Benefit Rate (CBR) [ Time Frame: Up to 8 years ]
    Is defined as tumor responses (as assessed by the Investigators) of complete response (CR), partial response (PR) and durable stable disease (SD) (SD of ≥ 4 months duration).
  • Objective Response Rate (ORR) [ Time Frame: Up to 8 years ]
    Is defined as the percent of subjects whose best response is complete response (CR) or partial response (PR).
  • Progression-Free Survival (PFS) [ Time Frame: Up to 8 years ]
    Is defined as the time from the first dose of CC-90011 to the first occurrence of disease progression or death from any cause.
  • Overall Survival (OS) [ Time Frame: Up to 8 years ]
    Is measured as the time from the first dose of CC-90011 to death due to any cause.
  • Pharmacokinetics - Cmax [ Time Frame: Up to 6 years ]
    Maximum observed plasma concentration
  • Pharmacokinetics - AUC [ Time Frame: Up to 6 years ]
    Area under the plasma concentration time-curve
  • Pharmacokinetics -Tmax [ Time Frame: Up to 6 years ]
    Time to maximum plasma concentration
  • Pharmacokinetics -t1/2 [ Time Frame: Up to 6 years ]
    Terminal half-life
  • Pharmacokinetics -CL/F [ Time Frame: Up to 6 years ]
    Apparent total body clearance
  • Pharmacokinetics -Vz/F [ Time Frame: Up to 6 years ]
    Apparent volume of distribution
Original Secondary Outcome Measures  ICMJE
 (submitted: August 18, 2016)
  • Clinical Benefit Rate (CBR) [ Time Frame: Up to 5 years ]
    Is defined as tumor responses (as assessed by the Investigators) of complete response (CR), partial response (PR) and durable stable disease (SD) (SD of ≥ 4 months duration).
  • Objective Response Rate (ORR) [ Time Frame: Up to 5 years ]
    Is defined as the percent of subjects whose best response is complete response (CR) or partial response (PR).
  • Progression-Free Survival (PFS) [ Time Frame: Up to 5 years ]
    Is defined as the time from the first dose of CC-90011 to the first occurrence of disease progression or death from any cause.
  • Overall Survival (OS) [ Time Frame: Up to 5 years ]
    Is measured as the time from the first dose of CC-90011 to death due to any cause.
  • Pharmacokinetics - Cmax [ Time Frame: Up to 5 years ]
    Maximum observed plasma concentration
  • Pharmacokinetics - AUC [ Time Frame: Up to 5 years ]
    Area under the plasma concentration time-curve
  • Pharmacokinetics -Tmax [ Time Frame: Up to 5 years ]
    Time to maximum plasma concentration
  • Pharmacokinetics -t1/2 [ Time Frame: Up to 5 years ]
    Terminal half-life
  • Pharmacokinetics -CL/F [ Time Frame: Up to 5 years ]
    Apparent total body clearance
  • Pharmacokinetics -Vz/F [ Time Frame: Up to 5 years ]
    Apparent volume of distribution
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Safety and Efficacy Study of CC-90011 in Subjects With Relapsed and/or Refractory Solid Tumors and Non-Hodgkin's Lymphomas
Official Title  ICMJE A Phase 1, Open-label, Dose Finding Study to Assess the Safety, Tolerability, Pharmacokinetic and Preliminary Efficacy of CC-90011 in Subjects With Advanced Solid Tumors and Non-Hodgkin Lymphomas
Brief Summary Study CC-90011-ST-001 is an open-label, Phase 1, dose escalation and expansion, First-In-Human (FIH) clinical study of CC-90011 in subjects with advanced unresectable solid tumors (enriched for grade 2 NENs, grade 2 NETs and NECs) and R/R NHL (MZL, including extranodal MZL [EMZL], splenic MZL [SMZL], nodal MZL [NMZL], and histologic transformation of MZL). The dose escalation part (Part A) of the study will explore escalating oral doses of CC-90011 to estimate the maximum tolerated dose (MTD) of CC-90011. The expansion part (Part B) will further evaluate the safety and efficacy of CC-90011 administered at or below the MTD in 3 selected expansion cohorts of approximately 10-20 evaluable subjects each, in order to further define the RP2D.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Lymphoma, Non-Hodgkin
  • Neoplasms
Intervention  ICMJE Drug: CC-90011
Study Arms  ICMJE Experimental: CC-90011 Administration
Subjects will administer CC-90011 orally once weekly in each 4 -week (28 day) Cycle. Alternative dosing schedules may be implemented based on the review of clinical safety and laboratory data by the SRC. CC-90011 will be administered with at least 240 mL of water. Subjects should fast for a minimum of 4 hours in both Parts A and B prior to CC-90011 administration and refrain from any food intake for up to 1 hour after dosing
Intervention: Drug: CC-90011
Publications * Hollebecque A, Salvagni S, Plummer R, Isambert N, Niccoli P, Capdevila J, Curigliano G, Moreno V, Martin-Romano P, Baudin E, Arias M, Mora S, de Alvaro J, Di Martino J, Parra-Palau JL, Sánchez-Pérez T, Aronchik I, Filvaroff EH, Lamba M, Nikolova Z, de Bono JS. Phase I Study of Lysine-Specific Demethylase 1 Inhibitor, CC-90011, in Patients with Advanced Solid Tumors and Relapsed/Refractory Non-Hodgkin Lymphoma. Clin Cancer Res. 2021 Jan 15;27(2):438-446. doi: 10.1158/1078-0432.CCR-20-2380. Epub 2020 Oct 12.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 9, 2021)
84
Original Estimated Enrollment  ICMJE
 (submitted: August 18, 2016)
70
Estimated Study Completion Date  ICMJE October 10, 2024
Estimated Primary Completion Date September 12, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Subjects must satisfy the following criteria to be enrolled in the study:

  1. ≥ 18 years of age
  2. Part A:

    - Subjects with histological or cytological confirmation of advanced unresectable solid tumors (including Grade 2 neuroendocrine neoplasms (NENs)/ neuroendocrine tumors (NETs), small cell lung cancer (SCLC), and other neuroendocrine carcinomas (NECs)) or R/R Non-Hodgkin's lymphomas (NHL) (diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL) or marginal cell lymphoma MZL))

  3. Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L without growth factor support for 7 days (14 days if subject received pegfilgastrim)

    • ANC ≥ 1.0 x 10^9/L (Part B, NHL cohort)
  4. Hemoglobin (Hgb) ≥ 10 g/dL (≥ 100 g/L or > 6.2 mmol/L)
  5. Platelet Count

    • Platelet count (plt) ≥ 100 x 109/L (≥ 50 x 10^9/L for NHL subjects) or ≥ 75 x 10^9/L for HCC or NEHCC subjects with portal hypertension without transfusion for 7 days (Part A).
    • Platelet count (plt) ≥ 150 x 10^9/L (Part B, solid tumor cohort in particular NET and CRPC).
    • Platelet count (plt) ≥ 50 x 10^9/L (Part B, NHL cohort)
  6. Part B:

Neuroendocrine tumors: Subjects with histological or cytological confirmation of advanced unresectable solid tumors (including low/intermediate-grade lung NETs, and Prostrate NECs (NEPCs)) which fall under one of the following categories:

B) Lung NETs:

Subjects with demonstrated tumor progression in the last 12 months on last prior therapy assessed by CT/MRI scan in the following 2 histologies.

i. Typical carcinoid (TC) ii. Atypical carcinoid (AC)

C) Prostate NECs (NEPCs):

  1. Appropriate pathological features according to WHO classification
  2. Expression of neuroendocrine markers
  3. Mitotic count ≥ 2 -10 per 10 HPF or ≥ 2-10 per 2mm2 and/or ≥ 3% Ki67 index (if reliably available)

D) R/R NHL:

Subjects with MZL (including EMZL, SMZL, NMZL and histologic transformation of MZL),relapsed/refractory after ≥2 prior therapies and ineligible for potentially curative therapy with the adequate immunohistochemistry markers.

Local therapy such as surgery, radiotherapy accounts for a first line treatment. Regarding gastric EMZL, antibiotics only does not count for one line of treatment. Prior therapies must contain at least one prior line with anti-CD20 antibody.

Subjects must have progressed on (or not been able to tolerate due to medical comorbidities or unacceptable toxicity), or following standard anticancer therapy or for whom no other approved conventional therapy exists or is acceptable

Exclusion Criteria:

The presence of any of the following will exclude a subject from enrollment:

  1. Low grade (G1) neuroendocrine tumors (<2 per high power fields (HPF) or < 2 per mm2 and/or ≤ 2% Ki67 index) such as carcinoid are excluded.
  2. Subject has received anti-cancer therapy (either approved or investigational) ≤ 4 weeks or 5 half-lives, whichever is shorter, prior to Cycle 1 Day 1.

    - < 42 days for prior nitrosureas or mitomycin C

  3. Toxicities resulting from prior systemic cancer therapies must have resolved to ≤National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 prior to starting CC-90011 treatment (with exception of grade 2 peripheral neuropathy and alopecia).
  4. Prior autologous stem cell transplant ≤ 3 months before first dose or those who have not recovered.
  5. Prior allogeneic stem cell transplant with either standard or reduced intensity conditioning.
  6. Subject has undergone major surgery ≤ 4 weeks or minor surgery ≤ 2 weeks prior to Cycle 1 Day 1 or who have not recovered from surgery.
  7. Subject has completed any radiation treatment < 4 weeks prior to Cycle 1 Day 1 or < 2 weeks for palliative bone radiotherapy (single fraction). Subjects with > 25% of myelopoetic BM radiation are not allowed to be enrolled on this study.
  8. 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 GI disorder that could affect the absorption of CC-90011.
  9. Subject with symptomatic or uncontrolled ulcers (gastric or duodenal), particularly those with a history of and/or risk of perforation and GI tract hemorrhages.
  10. Subject with any hemorrhage/bleeding event > CTCAE Grade 2 or haemoptysis > 1 teaspoon within 4 weeks prior to the first dose
  11. Symptomatic and untreated or unstable central nervous system (CNS) metastases as per protocol.
  12. Subject with SCLC that has history of interstitial lung disease (ILD) OR a history of pneumonitis that has required oral or Intra Venous (IV) steroids
  13. Subject has known symptomatic acute or chronic pancreatitis.
  14. Subject has impaired cardiac function or clinically significant cardiac diseases, as per protocol.
  15. Subject has other clinically significant heart disease such as congestive heart failure requiring treatment or uncontrolled hypertension (blood pressure ≥ 160/95 mm Hg).
  16. Subject is a pregnant or nursing female.
  17. Subject has known Human immunodeficiency virus (HIV) infection.
  18. Subject has known chronic active hepatitis B or C virus (HBV, HCV) infection.
  19. Subject with ongoing treatment with chronic, therapeutic dosing of anti-coagulants (eg, warfarin, low molecular weight heparin, Factor Xa inhibitors, thrombin antagonist). Low dose low molecular weight heparin for catheter maintenance and for short-term prophylaxis for subjects with prior PE and DVT are permitted under careful consideration by the Investigator.
  20. Subject has a history of concurrent second cancers requiring active, ongoing systemic treatment.
  21. Subject has any significant medical condition (eg, active or uncontrolled infection or renal disease), laboratory abnormality, or psychiatric illness that would prevent the subject from participating (or compromise compliance) in the study or would place the subject at unacceptable risk if he/she were to participate in the study.
  22. Subjects with poor bone marrow reserve as assessed by Investigator such as in the following conditions of (Part B only):

    • Having received extensive bone radiotherapy
    • Having experienced several episodes of bone marrow aplasia in previous treatments
    • Confirmed histological bone marrow cancer infiltration
    • Requiring regular hematopoietic support (blood transfusion, erythropoietin, GCSF).)
  23. Subject has any condition that confounds the ability to interpret data from the study.
  24. Previous SARS-CoV-2 infection within 10 days for mild or asymptomatic infections or 20 days for severe/critical illness prior to C1D1.

    • Acute symptoms must have resolved and based on investigator assessment in consultation with the Medical Monitor, there are no sequelae that would place the subject at a higher risk of receiving study treatment.

  25. Previous SARS-CoV-2 vaccine within 14 days of C1D1.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Associate Director Clinical Trial Disclosure 1-888-260-1599 clinicaltrialdisclosure@celgene.com
Listed Location Countries  ICMJE France,   Italy,   Japan,   Spain,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02875223
Other Study ID Numbers  ICMJE CC-90011-ST-001
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Celgene
Study Sponsor  ICMJE Celgene
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Zariana Nikolova, MD, PhD Celgene Corporation
Principal Investigator: Johann De Bono, MD, PhD Royal Marsden NHS Foundation Trust
Principal Investigator: Antoine Hollebecque, MD Gustave Roussy, Cancer Campus, Grand Paris
PRS Account Celgene
Verification Date July 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP