NeoplasmsPhase 1NCT01270906
Safety of CHIR-258 (TKI258) in Advanced Solid Tumors
A Phase 1 study testing CHIR-258 (TKI258) in people with Neoplasms and Cancer, run by Novartis Pharmaceuticals at 2 sites in United Kingdom.
Trial summary
Phase I dose finding study in solid tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- What is being tested?
- CHIR-258 (TKI258)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- Dec 2003to Oct 2006
- 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
- Diagnosis of histologically or cytologically documented, advanced-stage, primary or metastatic solid tumors that are refractory to standard therapy or for which no curative standard therapy exists.
- Evidence of measurable or evaluable disease.
- All acute toxic affects of any prior radiotherapy, chemotherapy, or surgical procedures must have resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, Version 3.0) Grade ≤1; surgery must have occurred at least 28 days prior to study enrollement.
- Age must be at least 18 years.
- Last dose of antineoplastic therapy (except for hormonal therapy) must be more than 21 days; subjects may continue to receive luteinizing hormone-releasing hormone analog therapy for prostate cancer.
- ECOG performance status must be 0 or 1.
- Life expectancy of at least 3 months.
- Patient must meet protocol-specified laboratory values.
Who cannot join
- Concurrent therapy with any other investigational agent.
- Intracranial edema, intracranial metastasis, or epidural disease.
- Pregnant or breastfeeing women. Female subjects must agree to use effective contraception, must be surgically sterile, or must be postmenopausal. Male subjects must agree to use effective contraception or be surgically sterile. The definition of effective contraception will be based on the judgment of the investigator or a designated associate. All at-risk female subjects must have a netative pregnancy test (serum or urine) within 10 days prior to the start of study treatment.
- Clinically significant cardiac disease (New York Heart Association Class III or IV) including pre-existing arrhythmia, congestive heart failure, cardiomyopathy, or subjects with baseline mean QTc interval greater than 450 msec (males) and 470 msec (females) or grade 2 or higher compromised left ventricular ejection fraction (LVEF) as determined by MUGA or ECHO.
- Dementia or altered mental status that would prohibit informed consent.
- Diabetes mellitus (insulin-dependent or -independent disease requiring chronic medication).
Show all 12Show fewer
- Previous pericarditis; clinically significant pleural effusion in the previous 12 months or current ascites requiring two or more interventions/month.
- Malabsorption syndrome or uncontrolled gastrointestinal toxicities (nausea, diarrhea, vomitting) with toxicity greater than NCI CTCAE grade 2.
- Prior acute or chonic pancreatitis of any etiology.
- Prior intra-or extra-hepatic biliary obstruction wtihin the previous 12 months or history of malignant obstruction requiring a bilary stent, unless stably treated with no prior obstruction or blockage of the stent.
- Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study-drug administration or may interfere with the interpretation of study results and, in the judgment of the investigator, make the subject inappropriate for this study.
- Other protocol-defined inclusion/exclusion criteria may apply
Trial locations and contacts
2 sites in 1 country.
United Kingdom2 sites
Novartis Investigative Site
Glasgow
Novartis Investigative Site
Sutton
About this study
Official title: A Phase 1 Dose Escalating Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodyniamics of CHIR-258 in Subjects With Advanced Solid Tumor Malignancies
Phase I dose finding study in solid tumors.
- Being tested
- CHIR-258 (TKI258)
- Keywords
- Neoplasms, Cancer, Tumors, Administration, oral, CHIR258, CHIR-258, CHIR 258, TKI258, TKI-258, TKI 258, dose finding
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CHIR-258 (TKI258)Drug
| Study group | Role | What they receive |
|---|---|---|
| CHIR-258 (TKI258) | Experimental | Not described Receives: Drug: CHIR-258 (TKI258) |
What is being measured
The primary outcome is the main question the study is designed to answer.
dose limiting toxicity (DLT) to define the maximum tolerated dose (MTD). The DLT is defined as treatment related grade 3 or grade 4 adverse events or abnormal lab test that occurred in the first 28 days after start of study drug.
Measured: continuous monitoring for the first 28 days after start of the study medication
Secondary outcomes (4)
characterize pharmacokinetic (PK) profile of study drug after single and repeated doses. The PK profile includes maximum blood concentration (Cmax) and time to reach maximum blood concentration (Tmax).
Measured: day 1 and day 15 at the following timepoints: pre-drug and 30 minutes, 1, 2, 3, 4, 5, 6, and 8 hours after dose
Pharmacodynamics (PD) in terms of serine-threonine kinase phosphorylation inhibition in blood before and after dose
Measured: day 1 and day 15 at the following timepoints: pre-drug, 4 and 24 hours after dose
Antitumor activity by comparing baseline and post-treatment changes. Tumor assessment will be performed using the Response Evaluation Criteria in Solid Tumors (RECIST)
Measured: baseline and once every two months thereafter
urinary metabolic profiling - examination of the ratio of beta-hydroxycortisol/cortisol
Measured: 24 hour urine collection on day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jan 2011 (estimated)
- Study startDec 2003
- Primary completionOct 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for NeoplasmsStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Chiron Corporation
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01270906
- Sponsor's protocol ID
- CTKI258A2101 (CHIR-258-001)
- Status last verified
- Jan 2011
- First submitted
- 2 Dec 2010
- Last updated
- 5 Jan 2011
- Results posted
- No
Publications
Wang X, Kay A, Anak O, Angevin E, Escudier B, Zhou W, Feng Y, Dugan M, Schran H. Population pharmacokinetic/pharmacodynamic modeling to assist dosing schedule selection for dovitinib. J Clin Pharmacol. 2013 Jan;53(1):14-20. doi: 10.1177/0091270011433330. Epub 2013 Jan 24.
PubMed 23400739
Study at a glance
From the registry record, last updated by the sponsor on 5 Jan 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Dose Escalating Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodyniamics of CHIR-258 in Subjects With Advanced Solid Tumor Malignancies
- ClinicalTrials.gov ID
- NCT01270906
- Acronym / sponsor ID
- CTKI258A2101 (CHIR-258-001)
- Keywords
- Neoplasms, Cancer, Tumors, Administration, oral, CHIR258, CHIR-258, CHIR 258
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Collaborators
- Chiron Corporation
- Study start
- Dec 2003
- Primary completion
- Oct 2006 (actual)
- First posted
- 5 Jan 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.
Phase I dose finding study in solid tumors.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CHIR-258 (TKI258) | Experimental | Drug: CHIR-258 (TKI258) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Diagnosis of histologically or cytologically documented, advanced-stage, primary or metastatic solid tumors that are refractory to standard therapy or for which no curative standard therapy exists.
- Evidence of measurable or evaluable disease.
- All acute toxic affects of any prior radiotherapy, chemotherapy, or surgical procedures must have resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, Version 3.0) Grade ≤1; surgery must have occurred at least 28 days prior to study enrollement.
- Age must be at least 18 years.
- Last dose of antineoplastic therapy (except for hormonal therapy) must be more than 21 days; subjects may continue to receive luteinizing hormone-releasing hormone analog therapy for prostate cancer.
Key exclusion criteria (12 listed)
- Concurrent therapy with any other investigational agent.
- Intracranial edema, intracranial metastasis, or epidural disease.
- Pregnant or breastfeeing women. Female subjects must agree to use effective contraception, must be surgically sterile, or must be postmenopausal. Male subjects must agree to use effective contraception or be surgically sterile. The definition of effective contraception will be based on the judgment of the investigator or a designated associate. All at-risk female subjects must have a netative pregnancy test (serum or urine) within 10 days prior to the start of study treatment.
- Clinically significant cardiac disease (New York Heart Association Class III or IV) including pre-existing arrhythmia, congestive heart failure, cardiomyopathy, or subjects with baseline mean QTc interval greater than 450 msec (males) and 470 msec (females) or grade 2 or higher compromised left ventricular ejection fraction (LVEF) as determined by MUGA or ECHO.
- Dementia or altered mental status that would prohibit informed consent.
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 |
|---|---|---|
| CHIR-258 (TKI258) | Drug | CHIR-258 (TKI258) |
Primary outcome
dose limiting toxicity (DLT) to define the maximum tolerated dose (MTD). The DLT is defined as treatment related grade 3 or grade 4 adverse events or abnormal lab test that occurred in the first 28 days after start of study drug.
Time frame: continuous monitoring for the first 28 days after start of the study medication
4 secondary outcomes
characterize pharmacokinetic (PK) profile of study drug after single and repeated doses. The PK profile includes maximum blood concentration (Cmax) and time to reach maximum blood concentration (Tmax).
Time frame: day 1 and day 15 at the following timepoints: pre-drug and 30 minutes, 1, 2, 3, 4, 5, 6, and 8 hours after dose
Pharmacodynamics (PD) in terms of serine-threonine kinase phosphorylation inhibition in blood before and after dose
Time frame: day 1 and day 15 at the following timepoints: pre-drug, 4 and 24 hours after dose
Antitumor activity by comparing baseline and post-treatment changes. Tumor assessment will be performed using the Response Evaluation Criteria in Solid Tumors (RECIST)
Time frame: baseline and once every two months thereafter
urinary metabolic profiling - examination of the ratio of beta-hydroxycortisol/cortisol
Time frame: 24 hour urine collection on day 1
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2011.
- Derived from this study: PubMed 23400739Wang X, Kay A, Anak O, Angevin E, Escudier B, Zhou W, Feng Y, Dugan M, Schran H. Population pharmacokinetic/pharmacodynamic modeling to assist dosing schedule selection for dovitinib. J Clin Pharmacol. 2013 Jan;53(1):14-20. doi: 10.1177/0091270011433330. Epub 2013 Jan 24.
Related trials for Neoplasms
Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
RecruitingPhase 2
Tafasitamab With Acalabrutinib and Venetoclax for the Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Active, not recruitingPhase 1/2
Selumetinib in Treating Young Patients With Recurrent or Refractory Low Grade Glioma
Low Grade Glioma, Recurrent Childhood Pilocytic Astrocytoma
Enrolling by invitationPhase 2
A Single-Arm Study of Nimotuzumab Combined With NALIRIFOX as First-Line Treatment for Pancreatic Cancer
Pancreatic Cancer Metastatic
Recruiting
Methylation Profiling in Self-Samples for Identification of (Epi)Genetic Biomarkers for Gynecological Cancers
Gynaecological Cancers, Ovarian Cancer
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.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CHIR-258 (TKI258) in people with Neoplasms and Cancer, run by Novartis Pharmaceuticals at 2 sites in United Kingdom.
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 8 inclusion and 12 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: stopped early, as of the sponsor's last update on 5 Jan 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United Kingdom. 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 was stopped early. Results are not available in the source record.
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 (DLT) to define the maximum tolerated dose (MTD). The DLT is defined as treatment related grade 3 or grade 4 adverse events or abnormal lab test that occurred in the first 28 days after start of study drug. (time frame: continuous monitoring for the first 28 days after start of the study medication). 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 NCT01270906, which also lists 1 linked publication.
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 Jan 2011.