Glioblastoma MultiformePhase 1NCT01353625
Study to Assess Safety and Tolerability of Oral CC-115 for Patients With Advanced Solid Tumors, and Hematologic Malignancies.
A Phase 1 study testing CC-115 in people with Glioblastoma Multiforme and Squamous Cell Carcinoma of Head and Neck, run by Celgene at 17 sites in 4 countries.
Trial summary
The main purpose of this first human study with CC-115 is to assess the safety and action of a new class of experimental drug (dual DNA-PK and TOR kinase inhibitors) in patients with advanced tumors unresponsive to standard therapies and to determine the appropriate dose and tumor types for later-stage clinical… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma Multiforme, Squamous Cell Carcinoma of Head and Neck, Prostate Cancer
- What is being tested?
- CC-115
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 118 participants
- Where
- 17 sitesin 4 countries
- Study dates
- 25 Apr 2011to 12 Mar 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically-confirmed advanced solid tumor, chronic lymphocytic leukemia, small lymphocytic lymphoma, T-cell prolymphocytic leukemia, Non-Hodgkin Lymphoma or multiple myeloma
- Progressed or not tolerated standard therapy, and no further standard therapy is available
- Archival and screening tumor biopsy
- Eastern Cooperative Oncology Group Performance Status: 0 or 1
- Adequate organ function
Who cannot join
- Prior cancer-directed modalities or investigational drugs within 4 wks or 5 half lives, whichever is shorter
- Symptomatic brain metastases (prior treatment and stable metastases are allowed)
- Acute or chronic renal disease or pancreatitis
- Diarrhea ≥ Grade 2, impaired gastrointestinal absorption
- Impaired cardiac function
- History of diabetes requiring treatment, glucose >126 mg/dL, Glycated hemoglobin (HbA1c) ≥6.5%
Show all 11Show fewer
- Peripheral neuropathy ≥ Grade 2
- Known Human Immunodeficiency Virus (HIV) infection, chronic hepatitis B or C (unless associated with hepatocellular cancer)
- Pregnant, inadequate contraception, breast feeding
- Most concurrent second malignancies
- Part B only: Prior treatment with agents targeting both mammalian target of rapamycin (mTOR) complexes (dual mammalian target of rapamycin complex 1/2 inhibitors) and/or PI3K/AKT pathways. However, prior treatment with isolated target of rapamycin complex 1 (TORC1) inhibitors (eg., rapalogs) is allowed in both parts of this study.
Trial locations and contacts
17 sites in 4 countries.
17 sites in 4 countries
United States10 sites
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109
Mary Crowley Medical Research Center
Dallas, Texas, 75201
Henry Ford Medical Center - New Center One
Detroit, Michigan, 48202
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77303
Cedars-Sinai Medical Center
Los Angeles, California, 90048
UCLA
Los Angeles, California, 90095
Sarah Cannon Research Institute Drug Development Unit
Nashville, Tennessee, 37203
Memorial Sloan-Kettering Cancer Center
New York, New York, 10021
University of California, San Francisco Comprehensive Cancer Center and Cancer Research Institiute
San Francisco, California, 94115
Moffitt Cancer Center
Tampa, Florida, 33612
Spain4 sites
Hospital Val d'Hebron
Barcelona, 08035
Hospital Universitario Madrid Sanchinarro
Madrid, 28050
Hospital de Donosti
San Sebastián (Guipuzcoa), 20014
Hospital Virgen del Rocio
Seville, 41013
Germany2 sites
Uniklinik Koln
Cologne, 50937
Universitatsklinikum Wurzburg
Würzburg, 97070
About this study
Official title: A Phase 1a/1b, Multicenter, Open Label, Dosefinding Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of the Dual Dna-pk and Tor Kinase Inhibitor, Cc-115, Administered Orally to Subjects With Advanced Solid Tumors and Hematologic Malignancies
The main purpose of this first human study with CC-115 is to assess the safety and action of a new class of experimental drug (dual DNA-PK and TOR kinase inhibitors) in patients with advanced tumors unresponsive to standard therapies and to determine the appropriate dose and tumor types for later-stage clinical trials. The bioavailability of tablet and capsule formulations under fasting and fed conditions will also be evaluated in some patients.
Read the detailed description
Latest amendment clarifies that Chronic Lymophocytic Leukemia (CLL) includes T-cell Prolymphocytic Leukemia (T-PLL). Prior treatment with some drugs targeting mTOR, P13K and related pathways is now permitted.
- Conditions
- Glioblastoma Multiforme, Squamous Cell Carcinoma of Head and Neck, Prostate Cancer, Ewing's Osteosarcoma, Chronic Lymphocytic Leukemia, Neoplasm Metastasis
- Being tested
- CC-115
- Keywords
- Neoplasm, Malignancy, Carcinoma, Lymphoma, Leukemia, Multiple myeloma, mTOR kinase inhibitor, Castration-resistant prostate cancer, Hormone-resistant prostate cancer, Diffuse Large B-cell lymphoma
- Medical subject headings
- Glioblastoma, Squamous Cell Carcinoma of Head and Neck, Prostatic Neoplasms, Leukemia, Lymphocytic, Chronic, B-Cell, Neoplasm Metastasis, Neoplasms, Carcinoma, Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CC-115Drug
Part A (actively recruiting): Dose level starts with 0.5mg daily by mouth in cycles of 28 days. Level increases for different patient cohorts in 100% or 50% increments until optimal dose schedule is established for further study. Treatment continues for as long as patient benefits (i.e., until disease progression or unacceptable toxicity).
Part B: Optimal dose schedule is administered in 28-day cycles until disease progression.
| Study group | Role | What they receive |
|---|---|---|
| CC-115 | Experimental | Not described Receives: Drug: CC-115 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose-Limiting Toxicity
Measured: Continuously for 28 days after starting treatment
Non-Tolerated Dose
Measured: Continuously for 28 days after starting treatment
Maximum Tolerated Dose
Measured: Continuously for 28 days after starting treatment
Maximum Observed Concentration in Plasma of CC-115
Measured: Days 1, 2, 15, 16 of treatment
Area Under the Concentration-Time Curve for CC-115
Measured: Days 1, 2, 15 and 16 of treatment
Time to Maximum Concentration of CC-115
Measured: Days 1, 2, 15, and 16 of treatment
Terminal Half-Life for CC-115
Measured: Days 1, 2, 15, and 16 of treatment
Apparent Total Body Clearance of CC-115
Measured: Days 1, 2, 15 and 16 of treatment
Apparent Volume of Distribution of CC-115
Measured: Days 1, 2, 15, and 16 of treatment
Accumulation Index of CC-115
Measured: Days 1, 2, 15 and 16 of treatment
Secondary outcomes (2)
Pharmacodynamics
Phosphorylation inhibition determined by changes in the levels of multiple biomarkers including S6 and, 4EBP (for mTORC1), AKT (for mTORC2) and other appropriate biomarkers in circulating granulocytes and tumor tissue (when available).
Measured: Screening (within 28 days prior to first dose of study drug) and Days 1, 2, 8, 15, 22, 28, 155, and end of treatment
Anti-Tumor Efficacy
Tumor response rates using appropriate objective criteria for various malignancies
Measured: Every 2-3 months until proof of tumor progression
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2011 (estimated)
- Study start25 Apr 2011
- Primary completion12 Mar 2021
- Study completion12 Mar 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Glioblastoma MultiformeStudies of the same condition, open and under way.
- More trials run by CelgeneThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 118 participants (actual)
Sponsor and investigators
- Lead sponsor
- Celgene
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01353625
- Sponsor's protocol ID
- CC-115-ST-001
- Status last verified
- Sep 2021
- First submitted
- 12 May 2011
- Last updated
- 5 Oct 2021
- Results posted
- No
- Data monitoring committee
- No
Publications
Thijssen R, Ter Burg J, Garrick B, van Bochove GG, Brown JR, Fernandes SM, Rodriguez MS, Michot JM, Hallek M, Eichhorst B, Reinhardt HC, Bendell J, Derks IA, van Kampen RJ, Hege K, Kersten MJ, Trowe T, Filvaroff EH, Eldering E, Kater AP. Dual TORK/DNA-PK inhibition blocks critical signaling pathways in chronic lymphocytic leukemia. Blood. 2016 Jul 28;128(4):574-83. doi: 10.1182/blood-2016-02-700328. Epub 2016 May 27.
PubMed 27235137Munster P, Mita M, Mahipal A, Nemunaitis J, Massard C, Mikkelsen T, Cruz C, Paz-Ares L, Hidalgo M, Rathkopf D, Blumenschein G Jr, Smith DC, Eichhorst B, Cloughesy T, Filvaroff EH, Li S, Raymon H, de Haan H, Hege K, Bendell JC. First-In-Human Phase I Study Of A Dual mTOR Kinase And DNA-PK Inhibitor (CC-115) In Advanced Malignancy. Cancer Manag Res. 2019 Dec 13;11:10463-10476. doi: 10.2147/CMAR.S208720. eCollection 2019.
PubMed 31853198
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1a/1b, Multicenter, Open Label, Dosefinding Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of the Dual Dna-pk and Tor Kinase Inhibitor, Cc-115, Administered Orally to Subjects With Advanced Solid Tumors and Hematologic Malignancies
- ClinicalTrials.gov ID
- NCT01353625
- Acronym / sponsor ID
- CC-115-ST-001
- Conditions
- Glioblastoma Multiforme, Squamous Cell Carcinoma of Head and Neck, Prostate Cancer, Ewing's Osteosarcoma, Chronic Lymphocytic Leukemia, Neoplasm Metastasis
- Keywords
- Neoplasm, Malignancy, Carcinoma, Lymphoma, Leukemia, Multiple myeloma, mTOR kinase inhibitor, Castration-resistant prostate cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 118 participants (actual)
- Lead sponsor
- CelgeneIndustry (pharma, biotech, devices)
- Study start
- 25 Apr 2011 (actual)
- Primary completion
- 12 Mar 2021 (actual)
- Study completion
- 12 Mar 2021 (actual)
- First posted
- 13 May 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main purpose of this first human study with CC-115 is to assess the safety and action of a new class of experimental drug (dual DNA-PK and TOR kinase inhibitors) in patients with advanced tumors unresponsive to standard therapies and to determine the appropriate dose and tumor types for later-stage clinical trials. The bioavailability of tablet and capsule formulations under fasting and fed conditions will also be evaluated in some patients.
Detailed description
Latest amendment clarifies that Chronic Lymophocytic Leukemia (CLL) includes T-cell Prolymphocytic Leukemia (T-PLL). Prior treatment with some drugs targeting mTOR, P13K and related pathways is now permitted.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CC-115 | Experimental | Drug: CC-115 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Histologically-confirmed advanced solid tumor, chronic lymphocytic leukemia, small lymphocytic lymphoma, T-cell prolymphocytic leukemia, Non-Hodgkin Lymphoma or multiple myeloma
- Progressed or not tolerated standard therapy, and no further standard therapy is available
- Archival and screening tumor biopsy
- Eastern Cooperative Oncology Group Performance Status: 0 or 1
- Adequate organ function
Key exclusion criteria (11 listed)
- Prior cancer-directed modalities or investigational drugs within 4 wks or 5 half lives, whichever is shorter
- Symptomatic brain metastases (prior treatment and stable metastases are allowed)
- Acute or chronic renal disease or pancreatitis
- Diarrhea ≥ Grade 2, impaired gastrointestinal absorption
- Impaired cardiac function
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CC-115Part A (actively recruiting): Dose level starts with 0.5mg daily by mouth in cycles of 28 days. Level increases for different patient cohorts in 100% or 50% increments until optimal dose schedule is established for further study. Treatment continues for as long as patient benefits (i.e., until disease progression or unacceptable toxicity). Part B: Optimal dose schedule is administered in 28-day cycles until disease progression. | Drug | CC-115 |
Primary outcome
Dose-Limiting Toxicity
Time frame: Continuously for 28 days after starting treatment
Non-Tolerated Dose
Time frame: Continuously for 28 days after starting treatment
Maximum Tolerated Dose
Time frame: Continuously for 28 days after starting treatment
Maximum Observed Concentration in Plasma of CC-115
Time frame: Days 1, 2, 15, 16 of treatment
Area Under the Concentration-Time Curve for CC-115
Time frame: Days 1, 2, 15 and 16 of treatment
Time to Maximum Concentration of CC-115
Time frame: Days 1, 2, 15, and 16 of treatment
Terminal Half-Life for CC-115
Time frame: Days 1, 2, 15, and 16 of treatment
Apparent Total Body Clearance of CC-115
Time frame: Days 1, 2, 15 and 16 of treatment
Apparent Volume of Distribution of CC-115
Time frame: Days 1, 2, 15, and 16 of treatment
Accumulation Index of CC-115
Time frame: Days 1, 2, 15 and 16 of treatment
2 secondary outcomes
Pharmacodynamics
Time frame: Screening (within 28 days prior to first dose of study drug) and Days 1, 2, 8, 15, 22, 28, 155, and end of treatment
Anti-Tumor Efficacy
Time frame: Every 2-3 months until proof of tumor progression
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2021.
- Background: PubMed 27235137Thijssen R, Ter Burg J, Garrick B, van Bochove GG, Brown JR, Fernandes SM, Rodriguez MS, Michot JM, Hallek M, Eichhorst B, Reinhardt HC, Bendell J, Derks IA, van Kampen RJ, Hege K, Kersten MJ, Trowe T, Filvaroff EH, Eldering E, Kater AP. Dual TORK/DNA-PK inhibition blocks critical signaling pathways in chronic lymphocytic leukemia. Blood. 2016 Jul 28;128(4):574-83. doi: 10.1182/blood-2016-02-700328. Epub 2016 May 27.
- Derived from this study: PubMed 31853198Munster P, Mita M, Mahipal A, Nemunaitis J, Massard C, Mikkelsen T, Cruz C, Paz-Ares L, Hidalgo M, Rathkopf D, Blumenschein G Jr, Smith DC, Eichhorst B, Cloughesy T, Filvaroff EH, Li S, Raymon H, de Haan H, Hege K, Bendell JC. First-In-Human Phase I Study Of A Dual mTOR Kinase And DNA-PK Inhibitor (CC-115) In Advanced Malignancy. Cancer Manag Res. 2019 Dec 13;11:10463-10476. doi: 10.2147/CMAR.S208720. eCollection 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bristol-Myers Squibb study director
Bristol-Myers Squibb
17 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CC-115 in people with Glioblastoma Multiforme and Squamous Cell Carcinoma of Head and Neck, run by Celgene at 17 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in United States, Spain, Germany, France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose-Limiting Toxicity (time frame: Continuously for 28 days after starting treatment). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01353625, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2021.