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CBL0137 in Treating Patients With Advanced Extremity Melanoma or Sarcoma

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ClinicalTrials.gov Identifier: NCT03727789
Recruitment Status : Recruiting
First Posted : November 1, 2018
Last Update Posted : July 16, 2019
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Incuron
Information provided by (Responsible Party):
Roswell Park Cancer Institute

Tracking Information
First Submitted Date  ICMJE October 12, 2018
First Posted Date  ICMJE November 1, 2018
Last Update Posted Date July 16, 2019
Actual Study Start Date  ICMJE July 1, 2019
Estimated Primary Completion Date August 8, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 31, 2018)
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 ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03727789 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 31, 2018)
  • 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 ]
    Responses will be tabulated, and complete response rate will be estimated with its exact 80% confidence interval.
  • 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 ]
  • Duration of regional progression free survival (PFS) assessed by RECIST 1.1 [ Time Frame: Up to 24 months ]
  • Overall PFS assessed by RECIST 1.1 [ Time Frame: Up to 24 months ]
  • Incidence and type of adverse events assessed using NCI CTCAE v.5 [ Time Frame: Up to 24 months ]
  • Incidence of Adverse Events [ Time Frame: Baseline up to 24 months ]
    Changes in clinical laboratory values while receiving CBL0137
  • Incidence of Adverse events [ Time Frame: At pre- and post-intraarterial infusion assessed up to 24 months ]
    Drug safety
  • Tumor levels of p53^Ser392 and HSP70 assessed by enzyme-linked immunosorbent assay (ELISA) [ Time Frame: Up to 24 months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: October 31, 2018)
  • Quality of life (QOL) measured using the Functional Assessment of Cancer Therapy - Melanoma (FACT-M v.4) and the associated Melanoma Cancer subscale (MCS) [ Time Frame: Up to 24 months ]
    Median and range baseline subscale and total QOL scores, as well as single item scores, will be presented, followed by mean change scores for subscales, the total scale and single items, compared between different study intervention groups.
  • Quality of life (QOL) measured using the associated Melanoma Cancer subscale (MCS) [ Time Frame: Up to 24 months ]
    Median and range baseline subscale and total QOL scores, as well as single item scores, will be presented, followed by mean change scores for subscales, the total scale and single items, compared between different study intervention groups.
  • Melanoma-related symptoms measured using the FACT-M v.4 [ Time Frame: Up to 24 months ]
  • Melanoma-related symptoms measured using the associated Melanoma Cancer Subscale [ Time Frame: up to 24 months ]
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE CBL0137 in Treating Patients With Advanced Extremity Melanoma or Sarcoma
Official Title  ICMJE 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
Brief Summary 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE Drug: FACT Complex-targeting Curaxin CBL0137
Given IA
Other Name: CBL0137
Study Arms  ICMJE Experimental: Treatment (CBL0137)
Patients receive FACT complex-targeting curaxin CBL0137 IA over 15 minutes.
Intervention: Drug: FACT Complex-targeting Curaxin CBL0137
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 26, 2019)
36
Original Estimated Enrollment  ICMJE
 (submitted: October 31, 2018)
56
Estimated Study Completion Date  ICMJE August 8, 2022
Estimated Primary Completion Date August 8, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03727789
Other Study ID Numbers  ICMJE I 60017
NCI-2018-01928 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
I 60017 ( Other Identifier: Roswell Park Cancer Institute )
P30CA016056 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Roswell Park Cancer Institute
Study Sponsor  ICMJE Roswell Park Cancer Institute
Collaborators  ICMJE
  • National Cancer Institute (NCI)
  • Incuron
Investigators  ICMJE
Principal Investigator: Joseph Skitzki Roswell Park Cancer Institute
PRS Account Roswell Park Cancer Institute
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP