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A Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of CC-90010 in Subjects With Advanced Solid Tumors and Relapsed/Refractory Non-Hodgkin's Lymphomas

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ClinicalTrials.gov Identifier: NCT03220347
Recruitment Status : Recruiting
First Posted : July 18, 2017
Last Update Posted : February 12, 2018
Sponsor:
Information provided by (Responsible Party):
Celgene

Brief Summary:
Study CC-90010-ST-001 is an open-label, Phase 1a, dose escalation and expansion, First-in-human (FIH) clinical study of CC-90010 in subjects with advanced or unresectable solid tumors and relapsed and/or refractory advanced Non-Hodgkin's lymphoma (NHL). The dose escalation part (Part A) of the study will explore escalating oral doses of CC-90010 to estimate the maximum tolerated dose (MTD) of CC-90010. The expansion part (Part B) will further evaluate the safety and efficacy of CC-90010 administered at or below the MTD in selected expansion cohorts of approximately 20 evaluable subjects each in order to further define the recommended Phase 2 (RP2D) dose of CC-90010.

Condition or disease Intervention/treatment Phase
Lymphoma, Non-Hodgkin Neoplasms Drug: CC-90010 Phase 1

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-90010. 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-90010.

Treatment Period:

During the Treatment Period, CC-90010 will initially be administered orally once daily for 3 consecutive days followed by 4 consecutive days off in each 28-day cycle. Alternative dosing schedules (eg, 2-days- on/5-days- off each week, 3-days-on/4-days-off every other week, 2-weeks-on/2-weeks-off, 4-days on/24 days off, 5-days on/23-days- off, etc.) may be evaluated one dosing schedule at a time or ≥ 2 dosing schedules given in parallel, based on the review of available safety, PK, pharmacodynamic (PD), and efficacy data by the SRC.

Follow-up Period:

In the Follow-up Period, subjects will be followed for 28 days (± 3 days) after the last dose of CC-90010 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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 115 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, Open-label, Dose-finding Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of CC-90010 in Subjects With Advanced Solid Tumors and Relapsed/Refractory Non-Hodgkin's Lymphomas
Actual Study Start Date : July 24, 2017
Estimated Primary Completion Date : May 13, 2020
Estimated Study Completion Date : April 15, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: CC-90010 in patients with solid tumors and NHL
Subjects will administer CC-90010 starting on Day 1 for 3 consecutive days followed by 4 consecutive days off drug every week (3/7-days schedule) in each 28 day cycle.
Drug: CC-90010
CC-90010 is an oral, potent and reversible inhibitor of the epigenetic target bromodomain and extra-terminal (BET) proteins.




Primary Outcome Measures :
  1. Adverse Events (AEs) [ Time Frame: Up to 3 years ]
    Number of participants with adverse events

  2. Dose Limiting Toxicities (DLTs) [ Time Frame: Up to 18 months ]
    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-90010.

  3. Maximum tolerated dose (MTD) [ Time Frame: Up to 2 years ]
    The 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.


Secondary Outcome Measures :
  1. 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 stable disease (SD) (SD of ≥ 4 months duration).

  2. Objective response rate (ORR) [ Time Frame: Up to 5 years ]
    Is defined as the percent of subjects whose best response is CR or PR.

  3. Duration of Response Rate [ Time Frame: Up to 5 years ]
    Is measured from the time when criteria for CR/PR are first met (whichever is first recorded) until the first date at which progressive disease is objectively documented

  4. Duration of stable disease [ Time Frame: Up to 5 years ]
    For subjects with best response of SD, duration of SD is measured from the first dose date until the criteria for progression are met

  5. Progression-free survival (PFS) [ Time Frame: Up to 5 years ]
    Is defined as the time from the first dose of CC-90010 to the first occurrence of disease progression or death from any cause.

  6. Overall survival [ Time Frame: Up to 5 years ]
    Is measured as the time from the first dose of CC-90010 to death due to any cause.

  7. Pharmacokinetic- Cmax [ Time Frame: Up to 3 years ]
    Maximum observed plasma concentration

  8. Pharmacokinetic- AUC [ Time Frame: Up to 3 years ]
    Area under the plasma concentration time-curve

  9. Pharmacokinetic- Tmax [ Time Frame: Up to 3 years ]
    Time to maximum plasma concentration

  10. Pharmacokinetic- t1/2 [ Time Frame: Up to 3 years ]
    Terminal half-life

  11. Pharmacokinetic- CL/F [ Time Frame: Up to 3 years ]
    Apparent clearance

  12. Pharmacokinetic- Vz/F [ Time Frame: Up to 3 years ]
    Apparent volume of distribution



Information from the National Library of Medicine

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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:

Principal Inclusion Criteria

  1. Age = or > 18 years.
  2. At least one site of measurable disease for subjects with solid tumors; bi-dimensionally measurable disease on cross sectional imaging with at least one lesion >1.5 cm for subjects with NHL. For subjects with rare malignancies evaluable disease can be considered.
  3. Tumor biopsies whenever safe and feasible will be collected in Part A. Subject consents to mandatory tumor biopsies (Screening and on treatment) in Part B, except for subjects with GBM. In exceptional circumstances an exemption waiver may be granted by the Sponsor for this criterion
  4. ECOG PS of 0 to 1.
  5. Either commit to true abstinence or agree to use effective contraceptive methods and follow pregnancy precautions.

Exclusion Criteria:

Principal Exclusion Criteria

  • 1. Subject has received anti-cancer therapy (either approved or investigational) within <or= 4 weeks or 5 half-lives, whichever is shorter prior to starting CC-90010.

    2. Toxicities resulting from prior systemic cancer therapies must have resolved. to ≤ NCI CTCAE Grade 1 prior to starting CC-90010 treatment 3. Subject has received autologous hematologic stem cell transplant (HSCT) <or= 3 months prior to starting CC-90010 treatment. Subjects with allogeneic HSCT will not be allowed on this protocol. 4. Major surgery <or= 4 weeks or minor surgery <or= 2 weeks prior to starting CC-90010 or subjects who have not recovered from surgery.

    5. Completed radiation treatment < 4 weeks prior to starting CC-90010. 6. Symptomatic, untreated, or unstable central nervous system (CNS) metastases. 7. Known symptomatic acute or chronic pancreatitis. 8. Impaired cardiac function or clinically significant cardiac diseases. 9. Pregnant or nursing females. 10. History of concurrent second cancers requiring active, ongoing systemic treatment.

    11. History of clinically significant cognitive disorder(s) or active cognitive disorder(s).

    12. Evidence of history of bleeding diathesis. 13. Subjects with known prior episodes of non-arteritic anterior ischemic optic neuropathy (NAION) should be excluded from the study. CC-90010 should be used with caution in subjects with retinitis pigmentosa 14. Any significant medical condition 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.

    15. Patients with poor bone marrow reserve as assessed by the Investigator such as in the following conditions:

  • Having received extensive bone radiotherapy
  • Having experienced several episodes of bone marrow aplasia in previous treatments
  • Confirmed histological bone marrow cancer infiltration (with exemption of NHL)
  • Requiring regular hematopoietic support (blood transfusion, erythropoietin, GCSF)

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): NCT03220347


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

Locations
France
Centre Georges Francois Leclerc Not yet recruiting
Dijon, France, 21079
Institut Gustave Roussy Hematologie Not yet recruiting
Villejuif, France, 94805
Spain
Hospital Vall d'Hebron Recruiting
Barcelona, Spain, 08035
Hospital Universitario Fundacion Jimenez Diaz Recruiting
Madrid, Spain, 28040
Hospital 12 de Octubre Recruiting
Madrid, Spain, 28041
Sponsors and Collaborators
Celgene
Investigators
Study Director: Zariana Nikolova, MD, PhD Celgene

Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT03220347     History of Changes
Other Study ID Numbers: CC-90010-ST-001
U1111-1194-8570 ( Registry Identifier: WHO )
2015-004371-79 ( EudraCT Number )
First Posted: July 18, 2017    Key Record Dates
Last Update Posted: February 12, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Celgene:
Non-Hodgkin's Lymphomas
Safety
Efficacy
CC-90010
Solid Tumors
Relapsed/Refractory

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases