CBL0137 in Treating Patients With Advanced Extremity Melanoma or Sarcoma

NCT03727789 | Terminated Phase 1 DMC FDA Drug

• 2 other identifiers: I 60017NCI-2018-01928
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

  Up to 24 months

Secondary Outcomes (8)

• Tumor response as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 modified for cutaneous, out-of-field, and deeper lesions

  Up to 24 months

• Duration of tumor response (both in the field of infusion therapy and out-of-field) assessed by RECIST 1.1

  Up to 24 months

• Duration of regional progression free survival (PFS) assessed by RECIST 1.1

  Up to 24 months

• Overall PFS assessed by RECIST 1.1

  Up to 24 months

• Incidence and type of adverse events assessed using NCI CTCAE v.5

  Up to 24 months

Other Outcomes (4)

• Quality of life (QOL) measured using the Functional Assessment of Cancer Therapy - Melanoma (FACT-M v.4) and the associated Melanoma Cancer subscale (MCS)

  Up to 24 months

• Quality of life (QOL) measured using the associated Melanoma Cancer subscale (MCS)

  Up to 24 months

• Melanoma-related symptoms measured using the FACT-M v.4

  Up to 24 months

Study Arms (1)

Treatment (CBL0137)

EXPERIMENTAL

Patients receive FACT complex-targeting curaxin CBL0137 IA over 15 minutes.

Drug: FACT Complex-targeting Curaxin CBL0137

Interventions

FACT Complex-targeting Curaxin CBL0137 DRUG

Given IA

Also known as: CBL0137

Treatment (CBL0137)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 OR
• Have undergone a previous Melphalan based regional therapy for which they did not have a complete response and, present with persistent, progressive, or recurrent disease.
• \* NOTE: Patients with indeterminate staging must be reviewed by the Principal Investigator prior to registration.
• 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 (including TVEC), whichever is longer
• 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 \[AJCC\] melanoma staging must be documented in patient's medical record, as determined by computed tomography \[CT\] of the chest, abdomen and pelvis, within six weeks prior to administration of study drug;
• Due to the heterogeneous nature of sarcoma, AJCC sarcoma staging is NOT required
• 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 modified 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 (with the exception of immunotherapy) during this time period for melanoma.
• 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 for sarcoma
• 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 modified 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 not receiving systemic therapy (with the exception of immunotherapy) during this time period for melanoma

You may not qualify if:

• 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 ((excluding prior catheter-related thrombus that has been adequately treated) 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 (excluding prior catheter-related thrombus that has been adequately treated) 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 active 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.

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead
• Incuron: collaborator

Study Sites (1)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

MeSH Terms

Interventions

CBLC137

Study Officials

• Joseph Skitzki

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2018
• First Posted: November 1, 2018
• Study Start: July 1, 2019
• Primary Completion: January 16, 2024
• Study Completion: January 16, 2024
• Last Updated: March 27, 2024

Record last verified: 2024-03

Locations

US (1)