About Bolder Science

Our mission is to provide healthcare professionals with unbiased clinical research information, easily.

Currently, you can access the following clinical trials being conducted worldwide:

359,057 studies
in
219 countries
Clinical trial information and results are updated daily from ClinicalTrials.gov. The latest data update was conducted on 01/20/2021.
 Menu
This website is for US healthcare professionals
close-icon

Log In to Bolder Science

logo-iconLog in with Doximity
or
Forgot Password

Don't have an account? Sign Up

close-icon

Please enter your email address.

You will receive a link to create a new password via email.

Log In

close-icon

Create an Account

logo-iconLog in with Doximity
or
(optional) ?

Welcome, !

Please complete the following 4 questions to ensure you receive the information that best suits your needs.

Specialties

Choose 1 or more specialties that you are interested in:

Subspecialties

You can specify a subspecialty for areas you selected (if available):

Clinical Trials of Interest

When I’m looking for information on clinical trials, I usually am interested in...

finding clinical trials in which to enroll my patients

Rarely Often

finding newly launched clinical trials (for all phases)

Rarely Often

updates on status changes for clinical trials

Rarely Often

pipeline molecules

Rarely Often

Drug Interventions

Enter up to 3 drug interventions you are currently interested in:

Clinical trial information and results are updated daily from ClinicalTrials.gov. The latest data update was conducted on 01/20/2021.
Previous Next skip
Back

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

Clinicaltrials.gov identifier NCT03220347

Recruitment Status Recruiting

First Posted July 18, 2017

Last update posted August 5, 2020

Save Trial
study description
Study Description

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 the following cohorts: Cohort 1: relapsed and/or refractory DLBCL approximately 20-25 evaluable subjects at 45 mg CC-90010 4-days-on/24-days-off in each 28-day cycle Cohort 2: advanced BCC -enrollment stopped due to recruitment challenges Cohort 3: relapsed and/or refractory DLBCL -approximately 15 evaluable subjects at 30mg CC-90010 3-dayson/11-days-offin each 28-day cycle The food effect assessment (Part C, Spain only) will evaluate the impact of food on CC-90010 when administered at the RP2D of 45 mg 4-days-on/24-days-off (180 mg per 28-day cycle), by comparison of the PK parameters following fasted and fed (high-fat, high-calorie meal) conditions.

  • Condition or Disease:Lymphoma, Non-Hodgkin
    Neoplasms
  • Intervention/Treatment: Drug: CC-90010
  • Phase: Phase 1
Detailed Description

Parts A, B and C 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 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 was initially administered orally once daily for 3 consecutive days followed by 4 consecutive days off drug every week (3/7-days schedule) in each 28-day cycle in Part A. Alternative dosing schedules (eg, 2-days-on/5-days- off each week, 3-days-on/4-days-off every other week, 4-days on/24 days off) 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. Following completion of dose escalation in Part A, selected expansion cohorts will receive CC-90010 in Part B. The SRC determined the RP2D for Part B to be 45 mg CC-90010 given once daily for 4 consecutive days on followed by 24 consecutive days off (4-days-on/24-days-off) in each 28-day cycle. A cohort s of up to approximately 20-25 subjects with relapsed and/or refractory DLBCL (Cohort 1) will be enrolled in Part B expansion. Enrollment in advanced BCC (Cohort 2) will be stopped due to recruitment challenges. An additional cohort of approximately 15 evaluable subjects with R/R DLBCL (Cohort 3) will be enrolled under an alternative dosing regimen of 30 mg CC-90010 3days-on/11-days off in each 28-day cycle. The food effect assessment (Part C, Spain only) will evaluate the impact of food on CC-90010 when administered at the RP2D of 45 mg 4-days-on/24-days-off, by comparison of PK parameters following fasted and fed (high-fat, high-calorie meal) conditions in approximately 24 subjects with advanced solid tumors. 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 Design
  • Study Type: Interventional
  • Estimated Enrollment: 140 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 2017
  • Estimated Primary Completion Date: August 2021
  • Estimated Study Completion Date: August 2023
Arms and interventions
Arm Intervention/treatment
Experimental: CC-90010 in patients with solid tumors and NHL
Subjects will be administered orally once daily for 3 consecutive days followed by 4 consecutive days off drug every week (3/7-days schedule) in each 28 day cycle in Part A. Alternative dosing schedules (eg, 2-days-on/5-days- off each week, 3-days-on/4-days-off every other week, 4-days on/24 days off) 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.		 Drug: CC-90010
CC-90010 is an oral, potent and reversible inhibitor of the epigenetic target bromodomain and extra-terminal (BET) proteins.
Outcome Measures
  • Primary Outcome Measures: 1. Adverse Events (AEs) [ Time Frame: Up to 5 years ]
    Number of participants with adverse events
  • 2. Dose Limiting Toxicities (DLTs) [ Time Frame: Up to 5 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-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 5 years ]
    Maximum observed plasma concentration on first and last day of dosing within a cycle
  • 8. Pharmacokinetic- AUC [ Time Frame: Up to 5 years ]
    Area under the plasma concentration time-curve on first and last day of dosing within a cycle
  • 9. Pharmacokinetic- Tmax [ Time Frame: Up to 5 years ]
    Time to maximum plasma concentration on first and last day of dosing within a cycle
  • 10. Pharmacokinetic- t1/2 [ Time Frame: Up to 5 years ]
    Terminal half-life on last day of dosing within a cycle
  • 11. Apparent Clearance [ Time Frame: Up to 5 years ]
    Apparent total systemic clearance to be estimated following the last dose in cycle 1
  • 12. Apparent Volume of Distribution [ Time Frame: Up to 5 years ]
    Apparent steady state volume of distribution to be estimated following the last dose in cycle 1
  • 13. Pharmacokinetic- AUClast [ Time Frame: Up to 5 years ]
    Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration
  • 14. Pharmacokinetic- AUC0-24 [ Time Frame: Up to 5 years ]
    Area under the plasma concentration-time curve calculated from time zero to 24 hours
  • 15. Pharmacokinetic- AUC0-∞ [ Time Frame: Up to 5 years ]
    Area under the concentration-time curve calculated from time zero to infinity
Eligibility Criteria
  • Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
  • Sexes Eligible for Study: All
  • Accepts Healthy Volunteers: No
Criteria

Inclusion Criteria:

1. Age = or > 18 years.

2. For subjects enrolling in food-effect assessment (Part C) only: a. Subject must agree
and be willing to consume a standard high-fat, high-calorie meal. b. Subject must be
willing to refrain from caffeine or xanthene-containing products (coffee, tea, cola,
chocolate, etc.) for 48 hours prior to dosing on Cycle 1 Day 4 and Cycle 2 Day 4 and
up to 24 hours post dose.

3. Subjects with histological or cytological confirmation of either:

1. In Part A, advanced or unresectable solid tumors or advanced relapsed and/or
refractory Non-Hodgkin lymphoma (ie, Diffuse large B-cell lymphoma and Follicular
lymphoma or Marginal zone lymphoma) including those who have progressed on (or
not been able to tolerate due to medical comorbidities or unacceptable toxicity)
standard anticancer therapy or for whom no other approved conventional therapy
exists.

2. In Part B dose expansion, - Cohorts 1 and 3: relapsed and/or refractory DLBCL
following at least 2 prior lines of therapy (e.g. have failed at least one line
of standard therapy and have received at least one prior line of salvage therapy)
OR have failed at least one prior line of standard therapy and are not eligible
for autologous stem cell transplant (ASCT) or have declined ASCT; transformed
lymphoma following chemotherapy for lower grade lymphoma and at least two
standard treatment regimen for DLBCL.

Subjects with two or more lines of systemic therapy must have been treated with and
have lack of response after chimeric antigen receptor (CAR) T-cell therapy, if such
therapy is available, OR be ineligible for CAR T-cell therapy at the time of
enrollment, OR subject declined CAR T-cell therapy.

- Cohort 2: advanced basal cell carcinoma including those who have progressed on (or
not been able to tolerate due to medicalcomorbidities or unacceptable toxicity)
standard anticancer therapy or for whom no other approved conventional therapy exists.

In Part C, advanced or unresectable solid tumors including those who have progressed
on (or not been able to tolerate due to medical comorbidities or unacceptable
toxicity) standard anticancer therapy or for whom no other approved conventional
therapy exist

4. 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.

5. Tumor biopsies whenever safe and feasible will be collected in Part A, except for
subjects with GBM. Subject consents to mandatory tumor biopsies (Screening and on
treatment) in Part B. In exceptional circumstances an exemption waiver may be granted
by the Sponsor for this criterion

6. ECOG PS of 0 to 1.

7. 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. Subject has received prior CAR T-cell therapy or other T-cell targeting treatment (approved or investigational) ≤ 4 weeks prior to starting CC-90010. 3. Toxicities resulting from prior systemic cancer therapies must have resolved. to ≤ NCI CTCAE Grade 1 prior to starting CC-90010 treatment 4. 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. 5. Major surgery <or= 4 weeks or minor surgery <or= 2 weeks prior to starting CC-90010 or subjects who have not recovered from surgery. 6. Completed radiation treatment < 4 weeks prior to starting CC-90010. 7. Symptomatic, untreated, or unstable central nervous system (CNS) metastases. 8. Known symptomatic acute or chronic pancreatitis. 9. Impaired cardiac function or clinically significant cardiac diseases. 10. Pregnant or nursing females. 12. History of concurrent second cancers requiring active, ongoing systemic treatment. 13. History of clinically significant cognitive disorder(s) or active cognitive disorder(s). 13. Evidence of history of bleeding diathesis. 14. 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 15. 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. 16. 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)

Contacts and Locations
Contacts

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

Locations
Show 11 Study Locations
Sponsors and Collaborators

Celgene

Investigators

Study Director: Zariana Nikolova, MD, PhD Celgene

More Information
  • Responsible Party: Celgene
  • ClinicalTrials.gov Identifier: NCT03220347 History of Changes
  • Other Study ID Numbers: CC-90010-ST-001, U1111-1194-8570, 2015-004371-79
  • First Posted: July 18, 2017 Key Record Dates
  • Last Update Posted: August 5, 2020
  • Last Verified: August 2020
  • 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: Safety
    Efficacy
    CC-90010     Non-Hodgkin's Lymphomas
    Solid Tumors
    Relapsed/Refractory
  • Additional relevant MeSH terms: Lymphoma Lymphoma, Non-Hodgkin
= Our trial