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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

NCT02875223

Description:

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 relapsed and/or refractory solid tumors (including neuroendocrine carcinomas (NEC)) and Non-Hodgkin's lymphomas (NHLs). 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.

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
  • Follicular Lymphoma
  • Marginal Zone Lymphoma
  • Neuroendocrine Carcinoma
  • Neuroendocrine Tumor
  • Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: CC-90011-ST-001
  • NCT ID: NCT02875223

Conditions

  • Lymphoma, Non-Hodgkin
  • Neoplasms

Interventions

DrugSynonymsArms
CC-90011CC-90011 Administration

Purpose

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 relapsed and/or refractory solid tumors (including neuroendocrine carcinomas (NEC)) and Non-Hodgkin's lymphomas (NHLs). 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.

Detailed Description

      Parts A and B will consist of 3 periods: Screening, Treatment and Follow-up. Screening Period
      The Screening Period starts 28 days (± 3 days) prior to first dose of CC-90011. The informed
      consent document (ICD) must be signed and dated by the subject and the administering staff
      prior to the start of any other study procedures. All screening tests and procedures must be
      completed within the 28 days (±3 days) prior to the first dose of CC-90011.

      Treatment Period During the Treatment Period, CC-90011 will initially be administered orally
      in each 4-week (28 day) Cycle.

      Follow-up Period In the Follow-up Period, subjects will be followed for 28 days (± 3 days)
      after the last dose of CC-90011 for safety.

      After the Safety Follow-up visit, all subjects will be followed every subsequent 3 months (±
      2 weeks) for survival follow-up for up until 2 years or until death, lost to follow-up, or
      the End of Trial, whichever occurs first.
    

Trial Arms

NameTypeDescriptionInterventions
CC-90011 AdministrationExperimentalCC-90011 will be administered once weekly in the morning on an empty stomach (ie, ≥ 1 hour before breakfast) with at least 240 mL of water after an overnight fast lasting ≥ 4 hours in both Parts A and B.
  • CC-90011

Eligibility Criteria

        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
             advanced Non-Hodgkin's lymphomas (NHL) (diffuse large B cell lymphoma (DLBCL) and
             follicular lymphoma (FL) or marginal cell lymphoma MZL).) 3. Part B:

          -  Enrichment for bronchial and prostate NENs will be targeted. Subjects with
             histological or cytological confirmation of advanced unresectable solid tumors
             (including G2 NENs/NETs, SCLC, and other NECs) which fall under one of the following
             categories (G1 NETs are excluded from this study):

          -  NECs and G2 NENs/NETs must have:

               1. Appropriate pathological features according to WHO classification

               2. Expression of neuroendocrine markers

               3. Mitotic count ≥ 2 per 10 HPF or ≥ 2 per 2mm2 and/or ≥ 3% Ki67 index

        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. Subject has any condition that confounds the ability to interpret data from the study.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose‐Limiting Toxicity (DLT)
Time Frame:Up to approximately 28 days
Safety Issue:
Description:Number of participants with DLT

Secondary Outcome Measures

Measure:Clinical Benefit Rate (CBR)
Time Frame:Up to 6 years
Safety Issue:
Description: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).
Measure:Objective Response Rate (ORR)
Time Frame:Up to 6 years
Safety Issue:
Description:Is defined as the percent of subjects whose best response is complete response (CR) or partial response (PR).
Measure:Progression-Free Survival (PFS)
Time Frame:Up to 6 years
Safety Issue:
Description:Is defined as the time from the first dose of CC-90011 to the first occurrence of disease progression or death from any cause.
Measure:Overall Survival (OS)
Time Frame:Up to 6 years
Safety Issue:
Description:Is measured as the time from the first dose of CC-90011 to death due to any cause.
Measure:Pharmacokinetics ‐ Cmax
Time Frame:Up to 6 years
Safety Issue:
Description:Maximum observed plasma concentration
Measure:Pharmacokinetics ‐ AUC
Time Frame:Up to 6 years
Safety Issue:
Description:Area under the plasma concentration time-curve
Measure:Pharmacokinetics ‐Tmax
Time Frame:Up to 6 years
Safety Issue:
Description:Time to maximum plasma concentration
Measure:Pharmacokinetics ‐t1/2
Time Frame:Up to 6 years
Safety Issue:
Description:Terminal half-life
Measure:Pharmacokinetics ‐CL/F
Time Frame:Up to 6 years
Safety Issue:
Description:Apparent total body clearance
Measure:Pharmacokinetics ‐Vz/F
Time Frame:Up to 6 years
Safety Issue:
Description:Apparent volume of distribution

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Celgene

Trial Keywords

  • Safety
  • CC-90011
  • Relapsed and/or Refractory Solid Tumors
  • Non-Hodgkin's Lymphomas

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