Safety, Dose Tolerance, Pharmacokinetics, and Pharmacodynamics Study of CPX-POM in Patients With Advanced Solid Tumors

Study Description

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Brief Summary:

This is a first-in-human, Phase I, multicenter, open label, dose escalation study to evaluate the DLTs and MTD and to determine the recommended Phase 2 dose (RP2D) of CPX-POM administered IV in patients with any histologically- or cytologically-confirmed solid tumor type.

Condition or disease	Intervention/treatment	Phase
Advanced Solid Tumors	Drug: CPX-POM	Phase 1

Detailed Description:

The study will initially employ an accelerated escalation design, with a single patient enrolled in each cohort (i.e., Single-Patient Cohorts). The initial patient will receive CPX-POM at a starting dose of 30 mg/m2. Doses will be escalated (doubling), until a ≥Grade 2 toxicity (with the exception of alopecia), is encountered. Subsequently that and all subsequent cohorts will follow a classical "3 + 3" dose escalation design.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	24 participants
Allocation:	Non-Randomized
Intervention Model:	Single Group Assignment
Intervention Model Description:	This is a Phase I, first-in-human, multicenter, open label, dose escalating study to evaluate the DLTs and MTD and to determine the recommended Phase 2 dose (RP2D) of CPX-POM administered IV in patients with any histologically- or cytologically-confirmed solid tumor type.
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Phase 1, First-in-Human, Safety, Dose Tolerance, Pharmacokinetics, and Pharmacodynamics Study of CPX-POM in Patients With Advanced Solid Tumors
Actual Study Start Date :	January 15, 2018
Estimated Primary Completion Date :	July 31, 2019
Estimated Study Completion Date :	July 31, 2019

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Accelerated Escalation Design	Drug: CPX-POM; CPX-POM
Experimental: "3+3" Dose Escalation Design	Drug: CPX-POM; CPX-POM

Outcome Measures

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Primary Outcome Measures :

1. Evaluate the dose limiting toxicities (DLTs) and maximum tolerated dose (MTD)of CPX-POM [ Time Frame: 21 days ]

   The primary objective of this study is to evaluate the dose limiting toxicities (DLTs) and maximum tolerated dose (MTD) of ciclopirox phosphoryloxymethyl ester (CPX-POM) administered intravenously (IV) and establish the CPX POM dose recommended for further investigation.

   A DLT will include some Grade 3 or 4 AEs if deemed related to study drug. In addition, any patient who is unable to receive 80% of the expected dose of CPX-POM (i.e., patients who are unable to receive at least 4 of the 5 scheduled doses) because of AEs will be considered to have a DLT.

   In order to identify any DLTs, safety assessments including AEs, physical examinations, vital signs, and clinical laboratory tests will be conducted during each study visit through Day 22.

   The MTD is defined as the dose BELOW that dose which causes DLTs in ≥33% of patients.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria Include:

1. Patient has histologically- or cytologically- confirmed metastatic or advanced-stage solid malignant tumor that is refractory to standard therapy. Patients should only be included if no therapy exists or if they have already received all standard therapies that would be potentially curative or might provide significant benefit.
2. Patient may have received up to 4 prior lines of cytotoxic chemotherapy or immunotherapy for their metastatic disease (e.g., docetaxel + doxorubicin ± cyclophosphamide), and also may have received additional prior endocrine therapy, as appropriate (e.g., for breast or prostate cancer), or non-myelosuppressive therapy (e.g., bevacizumab, trastuzumab).
3. Patient has experienced progressive disease during or following or was intolerant of their most recent treatment regimen. Supporting information about prior progressive disease will be collected, if available.
4. Patient is male or female aged ≥18 years.
5. Patient provided signed and dated informed consent prior to initiation of any study procedures.
6. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 (fully active, able to carry out all pre-disease activities without restriction) or 1 (unable to perform physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature), as assessed on Composite International Diagnostic Interview (CIDI), before the first dose of CPX-POM.
7. Patient has adequate renal function (creatinine ≤1.5 × the upper limit of normal [ULN]) or a glomerular filtration rate (GFR) of ≥50 mL/min).
8. Patient has adequate hepatic function, as evidenced by a total bilirubin ≤1.5 × ULN, aspartate transaminase (AST), and /or alanine transaminase (ALT) ≤3 × ULN or ≤5 ×ULN, if due to liver involvement by tumor.
9. Patient has adequate bone marrow function, as evidenced by hemoglobin ≥9.0 g/dL in the absence of transfusion within the previous 72 hours, platelet count ≥100×109cells/L, and absolute neutrophil count (ANC) ≥1.5×109 cells/L.
10. Patient has no significant ischemic heart disease or myocardial infarction (MI) within 6 months before the first dose of CPX-POM. The eligibility of patients with ventricular pacemakers for whom the QT interval may not be accurately measurable will be determined on a case-by-case basis by the Sponsor in consultation with the Medical Monitor.

11. Patient and his/her partner agree to use adequate contraception after providing written informed consent through 3 months after the last dose of CPX-POM, as follows:

    1. For women: Negative pregnancy test during Screening and at CIDI and compliant with a medically-approved contraceptive regimen during and for 3 months after the treatment period or documented to be surgically sterile or postmenopausal.
    2. For men: Compliant with a medically-approved contraceptive regimen during and for 3 months after the treatment period or documented to be surgically sterile. Men whose sexual partners are of child-bearing potential must agree to use 2 methods of contraception prior to study entry, during the study, and for 3 months after the treatment period.
12. Patient is willing and able to participate in the study and comply with all study requirements.

Exclusion Criteria Include:

Patients who meet any of the following exclusion criteria are not to be enrolled in this study

1. Patient has a history of risk factors for torsade de pointes (e.g., heart failure, hypokalemia, family history of long QT syndrome) or requires the use of concomitant medications that prolong the QT/QTc interval during study participation (refer to the following for examples: http://www.azcert.org/medical-pros/drug-lists/drug-lists.cfm).
2. Patient has an abnormal cardiac appearance/heart size, as evidenced by chest X-ray or computed tomography (CT) scan.
3. Patient has an uncontrolled or severe intercurrent medical condition.
4. Patient underwent major surgery within 4 weeks before the first dose of CPX-POM or received cancer-directed therapy (chemotherapy, radiotherapy, hormonal therapy, biologic or immunotherapy, etc.) or an investigational drug or device within 4 weeks (6 weeks for mitomycin C and nitrosoureas) or 5 half-lives of that agent (whichever is shorter) before the first dose of CPX-POM. A minimum of 10 days between termination of the investigational drug and administration of CPX-POM is required. In addition, any drug-related toxicity, with the exception of alopecia, should have recovered to ≤Grade 1.
5. If female, patient is pregnant or breast-feeding.
6. Patient has evidence of a serious active infection (e.g., infection requiring treatment with intravenous antibiotics).
7. Patient has an important medical illness or abnormal laboratory finding that, in the Investigator's opinion, would increase the risk of participating in this study.
8. Patient is taking warfarin.
9. Patient has a history of other malignancy treated with curative intent within the previous 5 years with the exception of adequately treated non-melanoma skin cancer or carcinoma in situ of the cervix. Subjects with previous invasive cancers are eligible if the treatment was completed more than 5 years prior to initiating current study treatment, and there is no evidence of recurrent disease.

Contacts and Locations

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Locations

United States, Colorado
Sarah Cannon Research Institute	Not yet recruiting
Denver, Colorado, United States, 80218
Contact: Kari Koga 720-754-4650 kari.koga@sarahcannon.com
Principal Investigator: Gerald Falchook
United States, Florida
Florida Cancer Specialists & Research Institute	Recruiting
Sarasota, Florida, United States, 34232
Contact: Michele LaRoc 941-377-9993 Mlaroc@flcancer.com
Principal Investigator: Manish Patel
United States, Tennessee
Tennessee Oncology PLLC	Recruiting
Nashville, Tennessee, United States, 37203
Contact: Rachell Bellamy 615-341-7851 Rachell.Bellamy@sarahcannon.com
Principal Investigator: Howard Burris

Sponsors and Collaborators

CicloMed LLC

Cmed Clinical Services

More Information

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Responsible Party:	CicloMed LLC
ClinicalTrials.gov Identifier:	NCT03348514 History of Changes
Other Study ID Numbers:	CPX-POM-01-001
First Posted:	November 21, 2017
Last Update Posted:	February 13, 2018
Last Verified:	November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Undecided

Studies a U.S. FDA-regulated Drug Product:		Yes
Studies a U.S. FDA-regulated Device Product:		No