Solid TumorsPhase 1NCT01496534
Phase Ib Study of Gemcitabine Plus Cisplatin or Carboplatin Plus Dovitinib in Patients With Advanced Solid Tumors
A Phase 1 study testing Cisplatin and Carboplatin in people with Solid Tumors and Bladder Cancer, run by Matthew Galsky at 1 site in United States.
Trial summary
This is a phase Ib dose escalation study of dovitinib given in combination with either gemcitabine plus cisplatin or carboplatin in patients with advanced solid tumors. Patients with advanced solid tumors, for whom treatment with gemcitabine plus cisplatin or carboplatin would otherwise be warranted, will be enrolled. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumors, Bladder Cancer
- What is being tested?
- Cisplatin and Carboplatin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2012to Sep 2013
- 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
- Written informed consent and HIPAA authorization for release of personal health information.
- Age ≥ 18 years at the time of consent.
- Karnofsky Performance Status of ≥ 70%.
- Advanced/metastatic solid tumor for which treatment with gemcitabine plus carboplatin or gemcitabine plus cisplatin would otherwise be warranted.
- Prior treatment with chemotherapy is permitted. Patients must not have received more than three prior chemotherapeutic regimens.
- Adequate organ function as determined by the following laboratory values:
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- Hemoglobin (Hgb) ≥ 9 g/dL
- Platelets ≥ 100 x 109/L
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
- Creatinine of ≤ 1.5 OR Calculated creatinine clearance of ≥ 60 cc/min for the cisplatin cohort.
- Calculated creatinine clearance of ≥ 30 cc/min for the carboplatin cohort.
- Bilirubin ≤ 1.5 x ULN
- Aspartate aminotransferase (AST, SGOT) ≤ 1.5 ULN
- Alanine Aminotransferase (ALT, SGPT) < 1.5 ULN
- INR ≤ 1.5 and a PTT within normal limits
- LVEF assessed by 2-D echocardiogram (ECHO) > 50% or lower limit of normal or multiple gated acquisition scan (MUGA) > 45% or lower limit of normal
Who cannot join
- Prior treatment with more than three prior chemotherapy regimens.
- Has had major surgery within 30 days of starting the study treatment
- Have active CNS metastases.
- No treatment with any investigational agent within 30 days prior to being registered for protocol therapy.
- Prior cancer treatment must be completed at least 30 days prior to being registered for protocol therapy and the subject must have recovered from the acute toxic effects of the regimen.
- Prior radiation therapy must be completed at least 30 days prior to being registered for protocol therapy.
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- Pregnant or breastfeeding.
- Clinically significant infections as judged by the treating investigator.
- Impaired cardiac function or clinically significant cardiac diseases
- Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of dovitinib (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
- Patients who are currently receiving anticoagulation treatment with therapeutic doses of warfarin
- Women of child-bearing potential, who are biologically able to conceive, not employing two forms of highly effective contraception.
- Fertile males not willing to use contraception
Trial locations and contacts
1 site in 1 country.
United States1 site
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
About this study
Official title: Phase Ib Study of Dovitinib in Combination With Gemcitabine Plus Cisplatin or Gemcitabine Plus Carboplatin in Patients With Advanced Solid Tumors
This is a phase Ib dose escalation study of dovitinib given in combination with either gemcitabine plus cisplatin or carboplatin in patients with advanced solid tumors. Patients with advanced solid tumors, for whom treatment with gemcitabine plus cisplatin or carboplatin would otherwise be warranted, will be enrolled. The dose of dovitinib will be escalated in successive cohorts using standard "3+3" dose escalation rules. Patients will continue treatment, in the absence of prohibitive toxicity, until disease progression. The study will define the recommended phase II dose of these combination regimens.
Read the detailed description
This is a phase Ib study of dovitinib given in combination with gemcitabine plus cisplatin or carboplatin in patients with advanced solid tumors. This study will utilize standard 3+3 dose escalation rules to define the recommended phase II dose. Dose escalation will proceed independently in the two cohorts (cisplatin cohort: gemcitabine + cisplatin + dovitinib; carboplatin cohort: gemcitabine + carboplatin + dovitinib). Patients will receive treatment for up to 6 cycles, in the absence of toxicity, until disease progression
Primary Objective:
To determine the recommended phase II dose of dovitinib given in combination with gemcitabine plus cisplatin or carboplatin.
Secondary Objectives:
- To determine the response rate to treatment as per Response Evaluation Criteria in Solid Tumors (RECIST)
- To determine the toxicity of treatment at per the Common Terminology for Adverse Events (CTCAE v4)
- To determine the pharmacokinetics of dovitinib in combination with gemcitabine plus cisplatin or carboplatin.
- Conditions
- Solid Tumors, Bladder Cancer
- Being tested
- Cisplatin, Carboplatin
- Keywords
- advanced solid tumors, bladder cancer, gemcitabine, cisplatin, carboplatin, solid tumors
- Medical subject headings
- Urinary Bladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CisplatinDrug
Also called TKI258
Gemcitabine 1000 mg/m2 IV on days 1 + 8 Cisplatin 70 mg/m2 IV day 1 Dovitinib given orally on days 1-5, 8-12 and 15-19. Treatment will be recycled every 21-days. The dose of dovitinib will be escalated in successive cohorts
CarboplatinDrug
Also called TKI258
Gemcitabine 1000 mg/m2 IV on days 1 + 8 Carboplatin AUC 5 IV day 1 Dovitinib given orally on days 1-5, 8-12 and 15-19. Treatment will be recycled every 21-days. The dose of dovitinib will be escalated in successive cohorts
| Study group | Role | What they receive |
|---|---|---|
| Cisplatin | Active comparator | Gemcitabine 1000 mg/m2 IV on days 1 + 8 Cisplatin 70 mg/m2 IV day 1 Dovitinib given orally on days 1-5, 8-12 and 15-19. Treatment will be recycled every 21-days. The dose of dovitinib will be escalated in successive cohorts. Receives: Drug: Cisplatin |
| Carboplatin | Active comparator | Gemcitabine 1000 mg/m2 IV on days 1 + 8 Carboplatin AUC 5 IV day 1 Dovitinib given orally on days 1-5, 8-12 and 15-19. Treatment will be recycled every 21-days. The dose of dovitinib will be escalated in successive cohorts. Receives: Drug: Carboplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recommended phase II dose of combination regimen
The primary objectives of this study are to determine the recommended phase II dose of dovitinib given in combination with gemcitabine plus carboplatin or cisplatin.
Measured: Within the first 21 days of treatment
Secondary outcomes (1)
Antitumor activity
A CT scan of the chest, abdomen, and pelvis will be performed after every 2 cycles (or sooner if there is evidence of disease progression) while on combination therapy until disease progression (eg, after cycle 2, after cycle 4, and after cycle 6). Response to treatment will be determined using RECIST.
Measured: After every 2 cycles (42 days) of combination therapy up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Dec 2011 (estimated)
- Study startJan 2012
- Primary completionSep 2013
- Study completionSep 2013
Why it stopped: toxicity of combination of medications
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Solid TumorsStudies of the same condition, open and under way.
- 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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Matthew Galsky
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Sponsor-investigator, Matthew Galsky, Icahn School of Medicine at Mount Sinai
- Investigators
- Matthew D. Galsky, M.D., Principal investigator, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01496534
- Sponsor's protocol ID
- GCO 11-0946
- Status last verified
- Nov 2013
- First submitted
- 12 Dec 2011
- Last updated
- 27 Nov 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
Turner N, Grose R. Fibroblast growth factor signalling: from development to cancer. Nat Rev Cancer. 2010 Feb;10(2):116-29. doi: 10.1038/nrc2780.
PubMed 20094046Knowles MA. Novel therapeutic targets in bladder cancer: mutation and expression of FGF receptors. Future Oncol. 2008 Feb;4(1):71-83. doi: 10.2217/14796694.4.1.71.
PubMed 18241002Sarker D, Molife R, Evans TR, Hardie M, Marriott C, Butzberger-Zimmerli P, Morrison R, Fox JA, Heise C, Louie S, Aziz N, Garzon F, Michelson G, Judson IR, Jadayel D, Braendle E, de Bono JS. A phase I pharmacokinetic and pharmacodynamic study of TKI258, an oral, multitargeted receptor tyrosine kinase inhibitor in patients with advanced solid tumors. Clin Cancer Res. 2008 Apr 1;14(7):2075-81. doi: 10.1158/1078-0432.CCR-07-1466.
PubMed 18381947
Study at a glance
From the registry record, last updated by the sponsor on 27 Nov 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase Ib Study of Dovitinib in Combination With Gemcitabine Plus Cisplatin or Gemcitabine Plus Carboplatin in Patients With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT01496534
- Acronym / sponsor ID
- GCO 11-0946
- Conditions
- Solid Tumors, Bladder Cancer
- Keywords
- advanced solid tumors, bladder cancer, gemcitabine, cisplatin, carboplatin, solid tumors
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: toxicity of combination of medications
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Matthew GalskyUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- Jan 2012
- Primary completion
- Sep 2013 (actual)
- Study completion
- Sep 2013 (actual)
- First posted
- 21 Dec 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.
This is a phase Ib dose escalation study of dovitinib given in combination with either gemcitabine plus cisplatin or carboplatin in patients with advanced solid tumors. Patients with advanced solid tumors, for whom treatment with gemcitabine plus cisplatin or carboplatin would otherwise be warranted, will be enrolled. The dose of dovitinib will be escalated in successive cohorts using standard "3+3" dose escalation rules. Patients will continue treatment, in the absence of prohibitive toxicity, until disease progression. The study will define the recommended phase II dose of these combination regimens.
Detailed description
This is a phase Ib study of dovitinib given in combination with gemcitabine plus cisplatin or carboplatin in patients with advanced solid tumors. This study will utilize standard 3+3 dose escalation rules to define the recommended phase II dose. Dose escalation will proceed independently in the two cohorts (cisplatin cohort: gemcitabine + cisplatin + dovitinib; carboplatin cohort: gemcitabine + carboplatin + dovitinib). Patients will receive treatment for up to 6 cycles, in the absence of toxicity, until disease progression
Primary Objective:
To determine the recommended phase II dose of dovitinib given in combination with gemcitabine plus cisplatin or carboplatin.
Secondary Objectives:
- To determine the response rate to treatment as per Response Evaluation Criteria in Solid Tumors (RECIST)
- To determine the toxicity of treatment at per the Common Terminology for Adverse Events (CTCAE v4)
- To determine the pharmacokinetics of dovitinib in combination with gemcitabine plus cisplatin or carboplatin.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cisplatin | Active comparator | Drug: CisplatinGemcitabine 1000 mg/m2 IV on days 1 + 8 Cisplatin 70 mg/m2 IV day 1 Dovitinib given orally on days 1-5, 8-12 and 15-19. Treatment will be recycled every 21-days. The dose of dovitinib will be escalated in successive cohorts. |
| Carboplatin | Active comparator | Drug: CarboplatinGemcitabine 1000 mg/m2 IV on days 1 + 8 Carboplatin AUC 5 IV day 1 Dovitinib given orally on days 1-5, 8-12 and 15-19. Treatment will be recycled every 21-days. The dose of dovitinib will be escalated in successive cohorts. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Written informed consent and HIPAA authorization for release of personal health information.
- Age ≥ 18 years at the time of consent.
- Karnofsky Performance Status of ≥ 70%.
- Advanced/metastatic solid tumor for which treatment with gemcitabine plus carboplatin or gemcitabine plus cisplatin would otherwise be warranted.
- Prior treatment with chemotherapy is permitted. Patients must not have received more than three prior chemotherapeutic regimens.
Key exclusion criteria (13 listed)
- Prior treatment with more than three prior chemotherapy regimens.
- Has had major surgery within 30 days of starting the study treatment
- Have active CNS metastases.
- No treatment with any investigational agent within 30 days prior to being registered for protocol therapy.
- Prior cancer treatment must be completed at least 30 days prior to being registered for protocol therapy and the subject must have recovered from the acute toxic effects of the regimen.
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 |
|---|---|---|
| CisplatinAlso: TKI258Gemcitabine 1000 mg/m2 IV on days 1 + 8 Cisplatin 70 mg/m2 IV day 1 Dovitinib given orally on days 1-5, 8-12 and 15-19. Treatment will be recycled every 21-days. The dose of dovitinib will be escalated in successive cohorts | Drug | Cisplatin |
| CarboplatinAlso: TKI258Gemcitabine 1000 mg/m2 IV on days 1 + 8 Carboplatin AUC 5 IV day 1 Dovitinib given orally on days 1-5, 8-12 and 15-19. Treatment will be recycled every 21-days. The dose of dovitinib will be escalated in successive cohorts | Drug | Carboplatin |
Primary outcome
Recommended phase II dose of combination regimen
Time frame: Within the first 21 days of treatment
The primary objectives of this study are to determine the recommended phase II dose of dovitinib given in combination with gemcitabine plus carboplatin or cisplatin.
1 secondary outcome
Antitumor activity
Time frame: After every 2 cycles (42 days) of combination therapy up to 3 years
Results and safety
The study was stopped early (reason given: toxicity of combination of medications). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Nov 2013.
- Background: PubMed 20094046Turner N, Grose R. Fibroblast growth factor signalling: from development to cancer. Nat Rev Cancer. 2010 Feb;10(2):116-29. doi: 10.1038/nrc2780.
- Background: PubMed 18241002Knowles MA. Novel therapeutic targets in bladder cancer: mutation and expression of FGF receptors. Future Oncol. 2008 Feb;4(1):71-83. doi: 10.2217/14796694.4.1.71.
- Background: PubMed 18381947Sarker D, Molife R, Evans TR, Hardie M, Marriott C, Butzberger-Zimmerli P, Morrison R, Fox JA, Heise C, Louie S, Aziz N, Garzon F, Michelson G, Judson IR, Jadayel D, Braendle E, de Bono JS. A phase I pharmacokinetic and pharmacodynamic study of TKI258, an oral, multitargeted receptor tyrosine kinase inhibitor in patients with advanced solid tumors. Clin Cancer Res. 2008 Apr 1;14(7):2075-81. doi: 10.1158/1078-0432.CCR-07-1466.
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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.
Matthew D. Galsky, M.D. principal investigator
Icahn School of Medicine at Mount Sinai
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Cisplatin and Carboplatin in people with Solid Tumors and Bladder Cancer, run by Matthew Galsky at 1 site in United States.
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 16 inclusion and 13 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 27 Nov 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 (reason given: toxicity of combination of medications). 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?
Recommended phase II dose of combination regimen (time frame: Within the first 21 days of treatment). 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 NCT01496534, which also lists 3 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 27 Nov 2013.