Safety, Dose Tolerance, Pharmacokinetics, and Pharmacodynamics Study of CPX-POM in Patients With Advanced Solid Tumors
Condition: Advanced Solid Tumors
MeSH terms: Neoplasms
Intervention: CPX-POM - 30 mg/m^2; CPX-POM - 60 mg/m^2; CPX-POM - 120 mg/m^2; CPX-POM - 240 mg/m^2; CPX-POM - 360 mg/m^2; CPX-POM - 600 mg/m^2; CPX-POM - 900 mg/m^2; CPX-POM - 1200 mg/m^2
Intervention description: CPX-POM; CPX-POM; CPX-POM; CPX-POM; CPX-POM; CPX-POM; CPX-POM; CPX-POM
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential 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)
Enrollment: 19.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        Inclusion Criteria Include:

          1. Patient is male or female aged ≥18 years.

          2. Patient provided signed and dated informed consent prior to initiation of any study
             procedures.

          3. 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).

          4. Patient has a predicted life expectancy of ≥3 months.

          5. Dose escalation cohorts only: Patient has adequate renal function (creatinine ≤1.5 ×
             the upper limit of normal [ULN]) or a glomerular filtration rate (GFR) of ≥50
             mL/min/1.73 m^2). Expansion cohort only: Patient has a GFR of ≥30 mL/min/1.73 m^2.

          6. 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.

          7. 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 ≥100×10^9cells/L,
             and absolute neutrophil count (ANC) ≥1.5×10^9 cells/L.

          8. Patient has no significant ischemic heart disease or myocardial infarction (MI) within
             6 months before the first dose of CPX-POM and currently has adequate cardiac function,
             as evidenced by a left ventricular ejection fraction of >50% as assessed by
             multi-gated acquisition (MUGA) or ultrasound/echocardiography (ECHO); and corrected QT
             interval (QTc) <470 msec by Fridericia (QTcF). 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.

          9. 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 Day 1 of each
                  treatment cycle 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.

         10. 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. Patients
             should not receive anti-emetic medications before and following Dose 1 of Cycle 1 for
             each treatment cohort. However, anti-emetics such as ondansetron or granisetron that
             have a mild QTc prolonging effect are allowed starting with Dose 2 of Cycle 1, if used
             with caution and attention to the approved labelling.

          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 (including
             uncontrolled brain metastases). Patients with stable brain metastases either treated
             or being treated with a stable dose of steroids/anticonvulsants, with no dose change
             within 4 weeks before the first dose of CPX-POM and no anticipated dose change, are
             allowed. The decision to exclude a patient from the study for an uncontrolled or
             severe intercurrent medical condition will be made by the Principal Investigator.
             Examples could include epilepsy, resistant infection, or any other neurological
             disease that would make clinical assessment difficult.

          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 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 active Hepatitis A infection.

          8. Patient known human immunodeficiency virus (HIV) or Hepatitis B or C infection, as
             such patients may be at increased risk for toxicity due to concomitant treatment and
             disease-related symptoms may preclude accurate assessment of the safety of CPX POM.

          9. 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.

         10. Patient is taking warfarin.

         11. 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. Patients 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.

         12. Patient has known allergy or hypersensitivity to components of CPX-POM.

         13. Patient is taking any iron replacement therapy administered IV, IM, or orally due to
             the potential for loss of anticancer activity due to drug and metabolites chelating
             iron.