Solid TumorsPhase 1NCT01379287
Dose-Escalation Safety and Pharmacokinetic Study of Iso-Fludelone in Patients With Advanced Solid Tumors
A Phase 1 study testing Iso-Fludelone in people with Solid Tumors, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.
Trial summary
Iso-fludelone is a type of chemotherapy drug called an epothilone. Epothilones are drugs that attach to proteins in your body called "tubulins". Tubulins help cells to grow, and are found in both normal and cancer cells. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumors
- What is being tested?
- Iso-Fludelone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Jun 2011to 31 Jan 2023
- 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
- Pathologic confirmation of malignancy at Memorial Sloan-Kettering Cancer Center
- Diagnosis of advanced stage, primary or metastatic adult solid tumors refractory to standard therapy or for which no curative standard therapy exists
- Evidence of radiographically measurable or non-measurable disease by RECIST 1.1 criteria.
- All acute toxic effects of any prior radiotherapy, chemotherapy, or surgical procedures must have resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, version 4.0) Grade ≤1
- Age must be ≥ 18 years
- Last dose of antineoplastic therapy except for hormonal therapy must be > 21 days.
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- Patients with brain metastasis that have been treated and clinically stable following intervention with neurological signs or symptoms resolved to CTCAEv4 Grade ≤1
- ECOG performance status must be 0 or 1.
- Required baseline laboratory data within 14 days of iso-fludelone administration include
- Hemoglobin ≥ 8.5 g/dL
- Absolute neutrophils count ≥ 1.5 x 109 /L
- Platelet count ≥ 75 x 109 /L
- Serum bilirubin < or = to 1.5 x ULN
- AST and ALT < or = to 2.5 x ULN
- Serum creatinine < or = to 1.5 x ULN
- Willing and able to comply with scheduled visits, treatment plan, and laboratory tests.
Who cannot join
- Pre-existing diarrhea uncontrolled with supportive care. Prior hemorrhagic diarrhea due to ulcerative colitis, inflammatory bowel disease or other cause. Active, uncontrolled peptic ulcer disease (patients maintained with ranitidine or its equivalent are acceptable to enroll).
- Pre-existing neurological disease (including but not limited to peripheral sensory or motor neuropathy, seizures, gait disturbances, or tremors/involuntary movements) of CTCAEv4 Grade ≥ 2 due to any cause.
- Hypersensitivity reaction (CTCAEv4 Grade ≥ 2) to prior therapy containing hydroxypropyl-β-cyclodextrin, ethanol, propylene glycol, or patient may not be safely administered ethanol (e.g., current history of ethanol abuse or concomitant administration of Antabuse®).
- Concurrent therapy with any other investigational agent.
- Pregnant or breast-feeding women. Female patients must agree to use effective contraception, must be surgically sterile, or must be postmenopausal. Male patients must agree to use effective contraception or be surgically sterile. The definition of effective contraception will be based on the judgment of the Principal Investigator or a designated associate. All at-risk female patients must have a negative serum pregnancy test within 10 days prior to the start of study treatment.
- Clinically significant cardiac disease (New York Heart Association, Class III or IV); prior myocarditis from any cause; pre-existing Grade 2 or higher arrhythmias ("non-urgent medical attention indicated").
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- Dementia or altered mental status that would prohibit informed consent.
- Patients with untreated central nervous system (CNS) metastases.
- Patients with known leptomeningeal metastasis
- 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 Principal Investigator, would make the patient inappropriate for this study.
- Pre-existing ophthalmologic conditions (including glaucoma; history of demyelinating disease; vasculitis; retinal vascular occlusion and any optic neuropathy).
- History (or family history) of long QT syndrome or QTc > 450 msec on baseline ECG.
Trial locations and contacts
1 site in 1 country.
United States1 site
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
About this study
Official title: A Phase I, Open-Label, Dose-Escalation Safety and Pharmacokinetic Study of Iso-Fludelone in Patients With Advanced Solid Tumors
Iso-fludelone is a type of chemotherapy drug called an epothilone. Epothilones are drugs that attach to proteins in your body called "tubulins". Tubulins help cells to grow, and are found in both normal and cancer cells. When research animals with cancer were given the study drug, Iso-fludelone, the drug attached itself to "tubulin" and slowed or stopped the cancer cells from growing. Other types of epothilones have been tested in cancer patients and were found to be safe. A similar epothilone drug and other drugs called taxanes are currently approved by the FDA for treating certain types of cancers.
The purpose of this study is to see the effects, good and/or bad, of this investigational drug, Iso-fludelone, on cancer. The term "investigational" means the study drug being tested has not been approved by the United States Food and Drug Administration (FDA) or other regulatory agencies. This study is the first time the investigators are using iso-fludelone in people. This is a Phase I study. In a Phase I study, the first people to receive the drug are given a fairly low dose.
- Conditions
- Solid Tumors
- Being tested
- Iso-Fludelone
- Keywords
- Iso-Fludelone, KOS-1803, Dose-Escalation, 10-202
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Iso-FludeloneDrug
Also called KOS-1803
Iso-fludelone will be administered IV over 6 hours (+/- 30 mins) on Day 1 of every 3 week cycle.
| Study group | Role | What they receive |
|---|---|---|
| Patients with Advanced Solid Tumors | Experimental | The trial was initially designed as a 3 hour IV infusion of iso-fludelone every 3 weeks with three dose-escalation stages (12 patients), however it has been amended to study iso-fludelone administered over 6 hours (+/- 30 minutes) every 3 weeks schedule. Receives: Drug: Iso-Fludelone |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the maximum tolerated dose (MTD)
The MTD is defined as the dose that results in DLT in 25% of all evaluable patients.
Measured: 2 years
To determine the dose limiting toxicity (DLT), safety
Toxicities and adverse events will be assessed using the NCI CTC version 4.0
Measured: 2 years
Secondary outcomes (2)
To evaluate the plasma pharmacokinetics of iso-fludelone when administered intravenously
All PK analyses will be performed using the WinNonlin computer program; version 5.3 Pharsight Corporation, Mountain View, CA). PK Model selection will be based on a visual inspection of goodness of fit plots (observations vs. predictions, residuals and weighted residuals vs. predictions). The assay values (concentrations vs times) will be used to calculate individual-specific elimination rate constant (Ke), time to maximum Iso-fludelone concentration (Tmax), maximum Iso-fludelone concentration (Cmax) and area under the concentration-time curve (AUC) values.
Measured: over 6 hours (+/- 30 minutes) on a day 1 every 21 days schedule
To describe and assess any preliminary evidence of anti-tumor activity of iso-fludelone
Measured: every 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2011 (estimated)
- Study start20 Jun 2011
- Primary completion31 Jan 2023
- Study completion31 Jan 2023
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 Solid TumorsStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe 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
- 29 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- University of Pittsburgh, Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Mrinal Gounder, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01379287
- Sponsor's protocol ID
- 10-202
- Status last verified
- Jan 2023
- First submitted
- 20 Jun 2011
- Last updated
- 2 Feb 2023
- Results posted
- No
Publications
Christner SM, Parise RA, Levine ED, Rizvi NA, Gounder MM, Beumer JH. Quantitative method for the determination of iso-fludelone (KOS-1803) in human plasma by LC-MS/MS. J Pharm Biomed Anal. 2014 Nov;100:199-204. doi: 10.1016/j.jpba.2014.08.007. Epub 2014 Aug 12.
PubMed 25168219
Study at a glance
From the registry record, last updated by the sponsor on 2 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Open-Label, Dose-Escalation Safety and Pharmacokinetic Study of Iso-Fludelone in Patients With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT01379287
- Acronym / sponsor ID
- 10-202
- Conditions
- Solid Tumors
- Keywords
- Iso-Fludelone, KOS-1803, Dose-Escalation, 10-202
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (estimated)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- University of Pittsburgh, Bristol-Myers Squibb
- Study start
- 20 Jun 2011 (actual)
- Primary completion
- 31 Jan 2023 (actual)
- Study completion
- 31 Jan 2023 (actual)
- First posted
- 23 Jun 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.
Iso-fludelone is a type of chemotherapy drug called an epothilone. Epothilones are drugs that attach to proteins in your body called "tubulins". Tubulins help cells to grow, and are found in both normal and cancer cells. When research animals with cancer were given the study drug, Iso-fludelone, the drug attached itself to "tubulin" and slowed or stopped the cancer cells from growing. Other types of epothilones have been tested in cancer patients and were found to be safe. A similar epothilone drug and other drugs called taxanes are currently approved by the FDA for treating certain types of cancers.
The purpose of this study is to see the effects, good and/or bad, of this investigational drug, Iso-fludelone, on cancer. The term "investigational" means the study drug being tested has not been approved by the United States Food and Drug Administration (FDA) or other regulatory agencies. This study is the first time the investigators are using iso-fludelone in people. This is a Phase I study. In a Phase I study, the first people to receive the drug are given a fairly low dose.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients with Advanced Solid Tumors | Experimental | Drug: Iso-FludeloneThe trial was initially designed as a 3 hour IV infusion of iso-fludelone every 3 weeks with three dose-escalation stages (12 patients), however it has been amended to study iso-fludelone administered over 6 hours (+/- 30 minutes) every 3 weeks schedule. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Pathologic confirmation of malignancy at Memorial Sloan-Kettering Cancer Center
- Diagnosis of advanced stage, primary or metastatic adult solid tumors refractory to standard therapy or for which no curative standard therapy exists
- Evidence of radiographically measurable or non-measurable disease by RECIST 1.1 criteria.
- All acute toxic effects of any prior radiotherapy, chemotherapy, or surgical procedures must have resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, version 4.0) Grade ≤1
- Age must be ≥ 18 years
Key exclusion criteria (12 listed)
- Pre-existing diarrhea uncontrolled with supportive care. Prior hemorrhagic diarrhea due to ulcerative colitis, inflammatory bowel disease or other cause. Active, uncontrolled peptic ulcer disease (patients maintained with ranitidine or its equivalent are acceptable to enroll).
- Pre-existing neurological disease (including but not limited to peripheral sensory or motor neuropathy, seizures, gait disturbances, or tremors/involuntary movements) of CTCAEv4 Grade ≥ 2 due to any cause.
- Hypersensitivity reaction (CTCAEv4 Grade ≥ 2) to prior therapy containing hydroxypropyl-β-cyclodextrin, ethanol, propylene glycol, or patient may not be safely administered ethanol (e.g., current history of ethanol abuse or concomitant administration of Antabuse®).
- Concurrent therapy with any other investigational agent.
- Pregnant or breast-feeding women. Female patients must agree to use effective contraception, must be surgically sterile, or must be postmenopausal. Male patients must agree to use effective contraception or be surgically sterile. The definition of effective contraception will be based on the judgment of the Principal Investigator or a designated associate. All at-risk female patients must have a negative serum pregnancy test within 10 days prior to the start of study treatment.
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 |
|---|---|---|
| Iso-FludeloneAlso: KOS-1803Iso-fludelone will be administered IV over 6 hours (+/- 30 mins) on Day 1 of every 3 week cycle. | Drug | Patients with Advanced Solid Tumors |
Primary outcome
To determine the maximum tolerated dose (MTD)
Time frame: 2 years
The MTD is defined as the dose that results in DLT in 25% of all evaluable patients.
To determine the dose limiting toxicity (DLT), safety
Time frame: 2 years
Toxicities and adverse events will be assessed using the NCI CTC version 4.0
2 secondary outcomes
To evaluate the plasma pharmacokinetics of iso-fludelone when administered intravenously
Time frame: over 6 hours (+/- 30 minutes) on a day 1 every 21 days schedule
To describe and assess any preliminary evidence of anti-tumor activity of iso-fludelone
Time frame: every 6 weeks
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 2 Feb 2023.
- Derived from this study: PubMed 25168219Christner SM, Parise RA, Levine ED, Rizvi NA, Gounder MM, Beumer JH. Quantitative method for the determination of iso-fludelone (KOS-1803) in human plasma by LC-MS/MS. J Pharm Biomed Anal. 2014 Nov;100:199-204. doi: 10.1016/j.jpba.2014.08.007. Epub 2014 Aug 12.
- Memorial Sloan Kettering Cancer CenterLink provided by the sponsor.
Related trials for Solid Tumors
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A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
Neoplasms
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A Safety and Efficacy Extension Study of Pertuzumab in Patients With Solid Tumors Previously Enrolled in a Hoffmann-La Roche-Sponsored Pertuzumab Clinical Trial
Solid Tumors
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IL-12 Genetically Engineered Myeloid Cells in Participants With Relapsed, Refractory Solid Tumors
Relapsed Solid Tumor Malignancies, Refractory Solid Tumor Malignancies
RecruitingObservational study
Immune Checkpoint Inhibitor Toxicity Risk Prediction in Solid Tumors
Malignant Solid Neoplasm
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.
Mrinal Gounder, MD principal investigator
Memorial Sloan Kettering Cancer Center
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 Iso-Fludelone in people with Solid Tumors, run by Memorial Sloan Kettering Cancer Center 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 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: finished, as of the sponsor's last update on 2 Feb 2023. 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 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?
To determine the maximum tolerated dose (MTD) (time frame: 2 years). The study lists 2 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 NCT01379287, 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 2 Feb 2023.