Clinical Trials /

A Phase 1 Study Evaluating the Safety, PK, and Clinical Effects of PT-112 in Subjects With Advanced Solid Tumors

NCT02266745

Description:

This is a Phase 1/2, open-label, multi-center, non-randomized, dose-escalation study to be conducted in two parts: the Dose Escalation Phase and the Dose Expansion Phase. The Dose Escalation Phase will determine the Maximum Tolerated Dose (MTD) and recommended Phase 2 dose(s) (RP2D) of PT-112 Injection and evaluate its safety and tolerability, and PK (pharmacokinetics). The Dose Escalation Phase and is no longer enrolling. The Dose Expansion Phase currently has two cohorts: one for the study of PT-112 in patients with thymoma and thymic carcinoma, and the second in the study of PT-112 in metastatic castrate-resistant prostate cancer (mCRPC). Condition or disease: Advanced Solid Tumors; Thymoma and Thymic Carcinoma; Metastatic Castrate Resistant Prostate Cancer (mCRPC) Intervention/treatment: Drug: PT-112 Injection Phase: Phase 1/2

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Phase 1 Study of PT-112 Injection in Subjects With Advanced Solid Tumors
  • Official Title: A Phase 1, Open-Label, Dose-Escalation Study Evaluating the Safety, Pharmacokinetics, and Clinical Effects of Intravenously Administered PT-112 Injection in Subjects With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: PT-112-101
  • NCT ID: NCT02266745

Conditions

  • Advanced Solid Tumors

Interventions

DrugSynonymsArms
PT-112 InjectionPT-112PT-112 injection

Purpose

This is a Phase I, open-label, multi-center, non-randomized, dose-escalation study to be conducted in two parts: the Dose Escalation Phase and the Dose Confirmation Phase. The Dose Escalation Phase will determine the Maximum Tolerated Dose (MTD) and recommended Phase 2 dose(s) (RP2D) of PT-112 Injection and evaluate its safety and tolerability, PK (pharmacokinetic) and preliminary clinical effects. The Dose Confirmation Phase will be a cohort expansion at or below the MTD of PT-112 Injection. Subjects who tolerate the drug and who do not experience progressive disease may continue to receive PT-112 Injection at the discretion of the Principal Investigator for up to 6 cycles. For subjects who tolerate PT-112 Injection and who experience an objective response or stable disease through 6 cycles, the Sponsor will continue to provide PT-112 Injection under a separate mechanism, e.g., an extension protocol.

Detailed Description

      This is a Phase I, open-label, multi-center, non-randomized, dose-escalation study to be
      conducted in two parts: the Dose Escalation Phase and the Dose Confirmation Phase. The Dose
      Escalation Phase will determine the Maximum Tolerated Dose (MTD) and recommended Phase 2
      dose(s) (RP2D) of PT-112 Injection and evaluate its safety and tolerability, PK
      (pharmacokinetic) and preliminary clinical effects. The Dose Confirmation Phase will be a
      cohort expansion at or below the MTD of PT-112 Injection. Subjects who tolerate the drug and
      who do not experience progressive disease may continue to receive PT-112 Injection at the
      discretion of the Principal Investigator for up to 6 cycles. For subjects who tolerate
      PT-112 Injection and who experience an objective response or stable disease through 6
      cycles, the Sponsor will continue to provide PT-112 Injection under a separate mechanism,
      e.g., an extension protocol.
    

Trial Arms

NameTypeDescriptionInterventions
PT-112 injectionExperimentalPT-112 Injection, administered by intravenous infusion
  • PT-112 Injection

Eligibility Criteria

        Key Inclusion Criteria:

          -  Pathologically confirmed advanced solid tumor for which standard therapy proven to
             provide clinical benefit does not exist or is no longer effective.

          -  Eastern Collaborative Oncology Group (ECOG) Performance Status of 0-1 (Appendix 1).

          -  Evaluable disease, either measurable on physical examination or imaging by Response
             Evaluation Criteria in Solid Tumors (RECIST v1.1, Appendix 2), or by informative
             tumor marker(s).

          -  Laboratory values at the Screening Visit:

               1. Absolute neutrophil count (ANC) ≥1,500/mm3;

               2. Platelets ≥100,000/mm3;

               3. Total bilirubin ≤1.5 × the upper limit of normal (ULN) (subjects with Gilbert's
                  Syndrome are allowed if direct bilirubin is within normal limits);

               4. Aspartate aminotransferase (AST [SGOT]) ≤2.5 × the ULN;

               5. Alanine aminotransferase (ALT [SGPT]) ≤2.5 × the ULN;

               6. Serum albumin ≥3.0 gm/dL;

               7. Serum creatinine ≤1.5 mg/dL or a measured creatinine clearance ≥60 mL/min; and
                  Negative serum β hCG (human chorionic gonadotropin) test in women of
                  childbearing potential (defined as women ≤50 years of age, or >50 years of age
                  with a history of amenorrhea for ≤12 months prior to study entry).

          -  Subjects with primary liver cancer or hepatic metastasis are eligible to enroll,
             provided that, at the Screening Visit, the following criteria are met:

               1. Total bilirubin is no higher than the ULN;

               2. AST and ALT are each ≤5 × the ULN;

               3. Severe liver dysfunction (Child-Pugh Class B or C) is not present; and

               4. Subjects with a history of esophageal bleeding have varices that have been
                  sclerosed or banded and no bleeding episodes have occurred during the prior 6
                  months.

          -  If there is a known history of brain metastases, either treated with radiation
             therapy or untreated, the metastatic disease must be stable in the judgment of the
             Principal Investigator and must not require ongoing treatment with corticosteroids or
             anticonvulsants.

          -  Willing and able to provide written Informed Consent and comply with the requirements
             of the study.

        Key Exclusion Criteria:

          -  Any cytotoxic chemotherapy within 21 days prior to initiation of study drug.

          -  Any immunomodulatory drug therapy, anti-neoplastic hormonal therapy (unless dose has
             been stable for 3 months prior to Baseline and will remain stable during the trial),
             immunosuppressive therapy, corticosteroids >20 mg/day prednisone or equivalent, or
             growth factor treatment (e.g., erythropoietin) within 14 days prior to initiation of
             study drug.

          -  Presence of an acute or chronic toxicity of prior chemotherapy, with the exception of
             alopecia, that has not resolved to ≤Grade 1, as determined by National Cancer
             Institute Common Toxicity Criteria for Adverse Effects (CTCAE) v 4.0
             (http://evs.nci.nih.gov/ftp1/CTCAE/About.html).

          -  Receipt of more than 3 prior regimens of cytotoxic chemotherapy for metastatic
             disease unless prior approval is granted by the Sponsor.

          -  Bone marrow reserve which, in the clinical judgment of the Principal Investigator, is
             not adequate for participation in this trial.

          -  Radiotherapy within 28 days prior to baseline.

          -  Receipt of radiotherapy to >25 % of bone marrow.

          -  Major surgery within 28 days prior to initiation of study drug.

          -  Life expectancy <12 weeks.

          -  Active bacterial, viral, or fungal infection requiring systemic therapy.

          -  Known human immunodeficiency virus or acquired immunodeficiency syndrome related
             illness.

          -  Clinically significant hearing impairment, as judged by the Principal Investigator.

          -  Uncontrolled congestive heart failure (New York Heart Association Classification 3 or
             4), angina, myocardial infarction, cerebrovascular accident, coronary/peripheral
             artery bypass graft surgery, transient ischemic attack, or pulmonary embolism within
             3 months prior to initiation of study drug.

          -  Unstable cardiac dysrhythmias or persistent prolongation of the corrected QT interval
             (QTc) (Fridericia) to >450 msec for males or >470 msec for females.

          -  Previous malignancy, except for non-squamous-cell carcinoma of skin or carcinoma
             in-situ of the uterine cervix, unless the tumor was treated with curative intent more
             than 2 years prior to study entry.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Determine the safety and tolerability, Dose Limiting Toxicity(ies) (DLT), Maximum Tolerated Dose (MTD), and recommended Phase 2 dose(s) (RP2D)
Time Frame:28-day cycle
Safety Issue:
Description:The primary endpoint is to determine the safety profile and MTD of PT-112 Injection. Assessments will include drug exposure; characterization of DLTs; characterization of the type, incidence, severity, seriousness, and relationship to treatment of adverse events (AEs), and effects on vital signs and laboratory parameters.

Secondary Outcome Measures

Measure:Document any observed anti-tumor effects
Time Frame:Day 1, Day 56 and every 56 days subsequently
Safety Issue:
Description:Subjects will be assessed for clinical activity of PT-112 Injection every 2 cycles by appropriate physical examination or computed tomography imaging techniques, using RECIST v1.1; and, where appropriate, informative tumor markers every cycle.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Phosplatin Therapeutics

Last Updated

November 9, 2016