Dose-Escalation Safety and Pharmacokinetic Study of Iso-Fludelone in Patients With Advanced Solid Tumors

NCT01379287 | Completed Phase 1

• 1 other identifier: 10-202
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief 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. 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

Keywords

Iso-Fludelone; KOS-1803; Dose-Escalation; 10-202

Outcome Measures

Primary Outcomes (2)

• To determine the maximum tolerated dose (MTD)

  The MTD is defined as the dose that results in DLT in 25% of all evaluable patients.

  2 years

• To determine the dose limiting toxicity (DLT), safety

  Toxicities and adverse events will be assessed using the NCI CTC version 4.0

  2 years

Secondary Outcomes (2)

• To evaluate the plasma pharmacokinetics of iso-fludelone when administered intravenously

  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

  every 6 weeks

Study Arms (1)

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.

Drug: Iso-Fludelone

Interventions

Iso-Fludelone DRUG

Iso-fludelone will be administered IV over 6 hours (+/- 30 mins) on Day 1 of every 3 week cycle.

Also known as: KOS-1803

Patients with Advanced Solid Tumors

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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").
• 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.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• University of Pittsburgh: collaborator
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Publications (1)

• 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.

  PMID: 25168219 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

Study Officials

• Mrinal Gounder, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 20, 2011
• First Posted: June 23, 2011
• Study Start: June 20, 2011
• Primary Completion: January 31, 2023
• Study Completion: January 31, 2023
• Last Updated: February 2, 2023

Record last verified: 2023-01

Locations

US (1)