Clinical Trials /

CBL0137 in Treating Patients With Advanced Extremity Melanoma or Sarcoma

NCT03727789

Description:

This phase I trial studies best dose and side effects of CBL0137 in treating patients with extremity melanoma or sarcoma that has spread to other places in the body. Drugs, such as CBL0137, may work by binding to tumor cell deoxyribonucleic acid (DNA) to stop the cell from growing further.

Related Conditions:
  • Melanoma
  • Sarcoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: CBL0137 in Treating Patients With Advanced Extremity Melanoma or Sarcoma
  • Official Title: A Single-Center Phase I Dose Escalation/Response Trial to Evaluate Safety, Tolerability, and Anti-Tumor Efficacy of Intra-Arterial CBL0137 for Patients With Advanced Extremity Melanoma or Sarcoma

Clinical Trial IDs

  • ORG STUDY ID: I 60017
  • SECONDARY ID: NCI-2018-01928
  • SECONDARY ID: I 60017
  • SECONDARY ID: P30CA016056
  • NCT ID: NCT03727789

Conditions

  • Advanced Cutaneous Melanoma of the Extremity
  • Advanced Sarcoma of the Extremity
  • Clinical Stage III Cutaneous Melanoma AJCC v8
  • Clinical Stage IV Cutaneous Melanoma AJCC v8
  • Pathologic Stage IIIB Cutaneous Melanoma AJCC v8
  • Pathologic Stage IIIC Cutaneous Melanoma AJCC v8
  • Pathologic Stage IV Cutaneous Melanoma AJCC v8
  • Recurrent Cutaneous Melanoma of the Extremity
  • Recurrent Sarcoma of the Extremity
  • Stage III Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8
  • Stage IIIA Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8
  • Stage IIIB Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8
  • Stage IV Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8

Interventions

DrugSynonymsArms
FACT Complex-targeting Curaxin CBL0137CBL0137Treatment (CBL0137)

Purpose

This phase I trial studies best dose and side effects of CBL0137 in treating patients with extremity melanoma or sarcoma that has spread to other places in the body. Drugs, such as CBL0137, may work by binding to tumor cell deoxyribonucleic acid (DNA) to stop the cell from growing further.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To estimate the maximum tolerated dose (MTD) and examine the dose-limiting toxicities of
      intra-arterial facilitates chromatin transcription (FACT) complex-targeting curaxin CBL0137
      (CBL0137) in patients with advanced extremity melanoma or sarcoma.

      SECONDARY OBJECTIVES:

      I. To assess the tumor response in advanced melanoma and sarcoma patients treated with
      intra-arterial administration of CBL0137.

      II. To define both response in-field (area of the limb distal to the infusion point) and
      out-of-field (any area proximal to the infusion point) in patients treated with CBL0137 based
      intra-arterial infusion.

      III. Assess the pharmacokinetics of CBL0137 in the study population pre-and post CBL0137
      intraarterial infusion.

      IV. Assess tumor protein expression profiles before and after treatment with CBL0137.

      TERTIARY OBJECTIVES:

      I. To assess if the proposed treatment has any effect on quality of life as measured by the
      Functional Assessment of Cancer Therapy ? Melanoma (assessment tool also applicable to
      sarcoma).

      OUTLINE: This is a dose-escalation study of FACT complex-targeting curaxin CBL0137.

      Patients receive FACT complex-targeting curaxin CBL0137 intra-arterially (IA) over 15
      minutes.

      After completion of study treatment, patients are followed up at 2, 6 and 12 weeks, every 3
      months for 12 months, then at 24 months.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (CBL0137)ExperimentalPatients receive FACT complex-targeting curaxin CBL0137 IA over 15 minutes.
  • FACT Complex-targeting Curaxin CBL0137

Eligibility Criteria

        Inclusion Criteria:

          -  Patient must have a life expectancy of > 6 months.

          -  Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.

          -  Patients either:

               -  Must not have undergone any limb-directed treatment.

               -  Have undergone a previous Melphalan based regional therapy for which they did not
                  respond optimally and, present with persistent, progressive, or recurrent
                  disease.

          -  Patient must have had a washout period for at least 30 days or 5 half-lives from any
             prior chemotherapy, radioactive or hormonal cancer therapy, or 4 weeks from any
             checkpoint inhibitors or other biologic, whichever is longer.

               -  NOTE: Patients with indeterminate staging must be reviewed by the Principal
                  Investigator prior to registration.

          -  Patient must have histologically proven primary or recurrent extremity melanoma (stage
             IIIB, IIIC, or IV), or advanced extremity sarcoma not amenable to surgical resection
             (American Joint Committee on Cancer [AJCC] staging must be documented in patient's
             medical record, as determined by computed tomography [CT] of the chest, abdomen and
             pelvis, and/or whole body positron emission tomography [PET] scan, within six weeks
             prior to administration of study drug).

          -  Patients with Stage IIIC disease must either have had regional lymph nodes previously
             removed or have stable or regressed disease on imaging from prior systemic therapy
             (defined as RECIST 1.1 SD, CR, or PR). Stable or regressed disease must be present for
             at least the 2 months prior to IA CBL0137 and patient is no longer receiving systemic
             therapy during this time period..

          -  Patients with Stage IV disease must have had all distant disease resected at least 30
             days prior to regional treatment, or exhibit stable or regressed disease .on imaging
             from prior systemic therapy (defined as RECIST 1.1 SD, CR, or PR). Stable or regressed
             disease must be present for at least the 2 months prior to IA CBL0137 and patient is
             no longer receiving systemic therapy during this time period.

          -  Melanoma patients who have stable or completely responded brain metastases from
             previous gamma knife surgery and/or systemic therapies are eligible.

          -  Patient's disease must be measured by caliper or radiological method as defined in the
             Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.

          -  Hemoglobin >= 9 g/dL.

          -  White blood count (WBC) of >= 3000 m^3.

          -  Absolute neutrophil count (ANC) >= 1,500/mm^3.

          -  Platelet count >= 100,000/mm^3.

          -  Total bilirubin =< 1.5 x upper limit of normal (ULN).

          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x the ULN.

          -  Creatinine clearance (CrCl) > 45 mL/minute.

          -  Patient must have a palpable femoral/radial pulse in the affected extremity.

          -  Recovery from relevant toxicity prior to first study drug administration.

          -  Participants of child-bearing potential must agree to use adequate contraceptive
             methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study
             entry. Should a woman become pregnant or suspect she is pregnant while she or her
             partner is participating in this study, she should inform her treating physician
             immediately.

          -  Ability to read and understand English and the ability to complete paper and/or
             electronic survey assessments.

          -  Participant or legal representative must understand the investigational nature of this
             study and sign an Independent Ethics Committee/Institutional Review Board approved
             written informed consent form prior to receiving any study related procedure.

        Exclusion Criteria:

          -  Cardiac disease: Congestive heart failure > Class II New York Heart Association
             (NYHA). Patients must not have unstable angina (angina symptoms at rest) or new onset
             angina (began within the last 3 months) or myocardial infarction within the past 6
             months

          -  Males with mean QTcF values of >450 msec and females with QTcF values of >470 msec,
             patients who are known to have congenital prolonged QT syndromes, or patients who are
             on medications known to cause prolonged QT intervals on ECG.

          -  Use of drugs known to prolong QT.

          -  Patients with known hypersensitivity to any of the components of CBL0137.

          -  Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic
             pressure > 90 mmHg, despite optimal medical management.

          -  Thrombotic or embolic events such as a cerebrovascular accident including transient
             ischemic attacks within the past 6 months.

          -  Patients with symptoms or signs of vascular insufficiency. Specifically, patients with
             any history of blood clots or lifestyle altering ischemic peripheral vascular disease
             will be excluded.

          -  Evidence or history of bleeding diathesis or coagulopathy.

          -  Patients with known heparin induced thrombocytopenia.

          -  Untreated or growing brain metastasis: Patients with neurological symptoms must
             undergo a CT scan/magnetic resonance imaging (MRI) of the brain to exclude untreated
             or growing brain metastasis.

          -  Known human immunodeficiency virus (HIV) infection or chronic hepatitis B or C.

          -  Active clinically serious infection > Common Terminology Criteria for Adverse Events
             (CTCAE) Grade 2.

          -  Serious non-healing wound, ulcer, or bone fracture.

          -  Major surgery or significant traumatic injury within 30 days of planned intra-arterial
             infusion.

          -  Current treatment or, treatment within the previous 24 months, for another
             non-melanoma or sarcoma malignancy.

          -  Patients who have already received 2 prior infusions of CBL0137.

          -  Pregnant or nursing female participants.

          -  Psychiatric conditions or diminished capacity that could compromise the giving of
             informed consent, or interfere with study compliance.

          -  Unwilling or unable to follow protocol requirements.

          -  Any condition which in the Investigator?s opinion deems the participant an unsuitable
             candidate to receive study drug.

          -  Received an investigational agent within 30 days prior to enrollment.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose-limiting toxicities (DLTs) defined based on the rate of drug-related grade 3-5 adverse events assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version (CTCAE) (v.) 5.
Time Frame:Up to 24 months
Safety Issue:
Description:The frequency of toxicities will be tabulated by grade across all dose levels. The frequency of toxicities will also be tabulated for the dose estimated to be the maximum tolerated dose.

Secondary Outcome Measures

Measure:Tumor response as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 modified for cutaneous, out-of-field, and deeper lesions
Time Frame:Up to 24 months
Safety Issue:
Description:Responses will be tabulated, and complete response rate will be estimated with its exact 80% confidence interval.
Measure:Duration of tumor response (both in the field of infusion therapy and out-of-field) assessed by RECIST 1.1
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Duration of regional progression free survival (PFS) assessed by RECIST 1.1
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Overall PFS assessed by RECIST 1.1
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Incidence and type of adverse events assessed using NCI CTCAE v.5
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Incidence of Adverse Events
Time Frame:Baseline up to 24 months
Safety Issue:
Description:Changes in clinical laboratory values while receiving CBL0137
Measure:Incidence of Adverse events
Time Frame:At pre- and post-intraarterial infusion assessed up to 24 months
Safety Issue:
Description:Drug safety
Measure:Tumor levels of p53^Ser392 and HSP70 assessed by enzyme-linked immunosorbent assay (ELISA)
Time Frame:Up to 24 months
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Roswell Park Cancer Institute

Last Updated

July 15, 2019