Clinical Trials /

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

NCT04608045

Description:

The expansion study is a Phase I, multicenter, open label feasibility trial to characterize the pharmacologic activity of IV CPX-POM in bladder tumor tissues obtained from patients with MIBC (Stage ≥T2, N0-N1, M0) who will be scheduled for RC with bilateral (standard or extended) pelvic lymph node dissection (PLND). The Dose Escalation study was a 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 and was completed.

Related Conditions:
  • Infiltrating Bladder Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Safety, Dose Tolerance, Pharmacokinetics, and Pharmacodynamics Study of CPX-POM in Patients With Advanced Solid Tumors
  • Official Title: A Phase 1, First-in-Human, Safety, Dose Tolerance, Pharmacokinetics, and Pharmacodynamics Study of CPX-POM in Patients With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: CPX-POM-01-001EXP
  • NCT ID: NCT04608045

Conditions

  • Advanced Solid Tumor

Interventions

DrugSynonymsArms
CPX-POMCPX-POM, 900 mg/m2 by 20 minute IV infusion

Purpose

The expansion study is a Phase I, multicenter, open label feasibility trial to characterize the pharmacologic activity of IV CPX-POM in bladder tumor tissues obtained from patients with MIBC (Stage ≥T2, N0-N1, M0) who will be scheduled for RC with bilateral (standard or extended) pelvic lymph node dissection (PLND). The Dose Escalation study was a 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 and was completed.

Detailed Description

      The expansion cohort of this study will be conducted at up to 3 study sites. It will be an
      open-label feasibility trial to characterize the pharmacologic activity of IV CPX-POM in
      bladder tumor tissues obtained from patients with MIBC (Stage ≥T2, N0-N1,M0) who will be
      scheduled for RC with bilateral (standard or extended) pelvic lymph node dissection (PLND).
      Approximately half of the patients enrolled will be cisplatin eligible and half will be
      chemotherapy eligible and scheduled to receive neoadjuvant chemotherapy with gemcitabine +
      cisplatin. Neoadjuvant treatment with CPX-POM, whether alone or in combination with
      gemcitabine +cisplatin, will start within 8 weeks of transurethral resection of the bladder
      tumor (TURBT) that showed muscularis propria invasion.

      Approximately 12 patients will be enrolled. Patients who are cisplatinin eligible will be
      treated with two 21-day treatment cycles of CPX-POM (Cycle 1, Days 1-5 treatment, rest days
      6-21; Cycle 2, Days 22-26 treatment, rest days 27-43) before a planned RC.
      Chemotherapy-eligible patients who are scheduled to receive neoadjuvant chemotherapy
      (gemcitabine + cisplatin in three 21-day treatment cycles) will be treated in addition with
      three 21-day treatment cycles of CPX-POM (Cycle 1, Days 1-5 treatment, rest days 6-21; Cycle
      2, Days 22-26 treatment, rest days 27-42; Cycle 3, Days 43-47, rest days 48-63), i.e.
      concurrently with the prescribed chemotherapy. The cisplatin + gemcitabine dosing regimen for
      chemotherapy-eligible patients in the Expansion Cohort will be administered per the
      institution's standard of care. After each infusion of CPX-POM, patients will remain in the
      clinic for at least a 1-hour observation period. On Day 1 of Cycle 1, single blood and clean
      catch urine samples will be collected prior to the first CPX-POM infusion.
    

Trial Arms

NameTypeDescriptionInterventions
CPX-POM, 900 mg/m2 by 20 minute IV infusionExperimental
  • CPX-POM

Eligibility Criteria

        Inclusion Criteria:

          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. 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.

         11. Patients must have histologically confirmed MIBC (≥T2, N0-N1, M0 per AJCC) pure or
             mixed histology urothelial carcinoma. Clinical node-positive (N1) patients are
             eligible provided the lymph nodes (LNs) are confined to the true pelvis and are within
             the planned surgical LN dissection template.

         12. The initial TURBT that showed muscularis propria invasion should be within 8 weeks
             prior to beginning study therapy, when feasible. There must be adequate evaluable
             tumor burden in the tissue blocks (from initial or repeat TURBT with highest tumor
             content) to allow for analysis as determined by the local site pathologist.

         13. Patients must be ineligible for cisplatin-based chemotherapy due to any of the
             following:

               1. Creatinine clearance(CrCl) <60 mL/min with Eastern Cooperative Oncology Group
                  (ECOG) Performance Status (PS) 0-1

               2. Hearing impaired ≥ Grade 2 by CTCAE criteria

               3. Neuropathy ≥ Grade 2 by CTCAE criteria

               4. Heart failure New York Heart Association (NYHA) ≥ III

        Exclusion Criteria:

        Patients who meet any of the following exclusion criteria are not to be enrolled in the
        Expansion Cohort.

          1. Baseline GFR <30 mL/min/1.73 m^2.

          2. Women must not be pregnant or breastfeeding since we do not know the effects of
             CPX-POM on the fetus or breastfeeding child.

          3. Patients may not have concurrent upper urinary tract (i.e. ureter, renal pelvis)
             invasive urothelial carcinoma. Patients with history of non-invasive (Ta, Tis) upper
             tract urothelial carcinoma that has been definitively treated with at least one
             post-treatment disease assessment (i.e. cytology, biopsy, imaging) that demonstrates
             no evidence of residual disease are eligible.

          4. Patients may not have another malignancy that could interfere with the evaluation of
             safety or efficacy of the study drugs. Patients with a prior malignancy will be
             allowed without study chair approval in the following circumstances:

               1. Not currently active and diagnosed at least 3 years prior to the date of
                  registration.

               2. Non-invasive diseases such as low risk cervical cancer or any cancer in situ.

               3. Localized (early stage) cancer treated with curative intent (without evidence of
                  recurrence and intent for further therapy), and in which no chemotherapy was
                  indicated.( (e.g. low/ intermediate risk prostate cancer, etc.).

          5. Patients may not have undergone major surgery with the exception of TURBT (e.g.
             intra-thoracic, intra-abdominal or intra-pelvic), open biopsy or significant traumatic
             injury or specific anti-cancer treatment ≤ 4 weeks prior to starting study drug, or
             patients who have had percutaneous biopsies or placement of vascular access device ≤ 1
             week prior to starting study drug, or who have not recovered from side effects of such
             procedure or injury.

          6. Patients must not have clinically significant cardiac disease.

          7. Patients may not have chronic active liver disease or evidence of acute or chronic
             Hepatitis B Virus (HBV) or Hepatitis C (HCV).

          8. Patients may not have known diagnosis of human immunodeficiency virus (HIV) infection.
             Testing is not required in absence of clinical suspicion.

          9. Patients may not have known diagnosis of any condition (e.g. post hematopoietic or
             solid organ transplant, pneumonitis, inflammatory bowel disease, etc.) that requires
             chronic immunosuppressive therapy. Usage of non-steroidal anti-inflammatory
             medications (NSAIDS) for the treatment of osteoarthritis and uric acid synthesis
             inhibitors for the treatment of gout are permitted.

         10. Patients with any serious and/or uncontrolled concurrent medical conditions (e.g..,
             active or uncontrolled infection, uncontrolled diabetes) or psychiatric illness that
             could, in the investigator's opinion, cause unacceptable safety risks or potentially
             interfere with the completion of the treatment according to the protocol are not
             eligible.

         11. Patients may not have any live viral vaccine used for prevention of infectious
             diseases within 4 weeks prior to study drug(s).

         12. Patients unwilling or unable to comply with the protocol.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:determine disease response following 2 or 3 CPX-POM treatment cycles by assessing the complete and partial pathologic response rate at the time of radical cystectomy (RC)
Time Frame:56 days
Safety Issue:
Description:Tumors will be assessed in a standard manner and given grade/stage according to the American Joint Commission on Cancer (AJCC) criteria. Efficacy will be assessed based on pathologic criteria and evidence of pharmacologic activity in the target tissue.

Secondary Outcome Measures

Measure:Number of Participant with any Serious Adverse Events (SAEs) as assessed by Common Terminology Criteria for Adverse Events (CTCAE version 4.03)
Time Frame:56 days
Safety Issue:
Description:Incidence of Serious Adverse Events in subjects receiving CPX-POM.
Measure:Number of Participant with any Adverse Events (AEs) as assessed by Common Terminology Criteria for Adverse Events (CTCAE version 4.03)
Time Frame:56 days
Safety Issue:
Description:Incidence of Adverse Events in subjects receiving CPX-POM.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:CicloMed LLC

Last Updated

October 28, 2020