Advanced Cutaneous Melanoma of the ExtremityPhase 1NCT03727789

CBL0137 in Treating Patients With Advanced Extremity Melanoma or Sarcoma

A Phase 1 study testing FACT Complex-targeting Curaxin CBL0137 in people with Advanced Cutaneous Melanoma of the Extremity and Advanced Sarcoma of the Extremity, run by Roswell Park Cancer Institute at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Advanced Cutaneous Melanoma of the Extremity, Advanced Sarcoma of the Extremity, Clinical Stage III Cutaneous Melanoma AJCC v8
What is being tested?: FACT Complex-targeting Curaxin CBL0137
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 7 participants
Where: 1 siteUnited States
Study dates: 1 Jul 2019to 16 Jan 2024
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

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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
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
Melanoma or sarcoma 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 measurable by caliper or radiological method as defined in the modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
Patient must have adequate bone marrow, liver and renal function as assessed by the following:
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.
Patients must have recovered from adverse events from previously administered agents (<=grade 2) 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 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.

Who cannot join

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.

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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.
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.

Trial locations and contacts

1 site in 1 country.

United States1 site

Roswell Park Cancer Institute
Buffalo, New York, 14263

Other trials in United States

About this study

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

Read the detailed description

PRIMARY OBJECTIVES:

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:

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:

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.

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
Being tested: FACT Complex-targeting Curaxin CBL0137

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

FACT Complex-targeting Curaxin CBL0137Drug
Also called CBL0137
Given IA

Study groups in NCT03727789
Study group	Role	What they receive
Treatment (CBL0137)	Experimental	Patients receive FACT complex-targeting curaxin CBL0137 IA over 15 minutes. Receives: Drug: FACT Complex-targeting Curaxin CBL0137

What is being measured

The primary outcome is the main question the study is designed to answer.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Jul 201916 Jan 2024

First posted1 Nov 2018
Study start1 Jul 2019
Primary completion16 Jan 2024
Study completion16 Jan 2024

Why it stopped: low accrual

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Advanced Cutaneous Melanoma of the ExtremityStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 7 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03727789
Sponsor's protocol ID: I 60017
Other IDs: NCI-2018-01928, I 60017
Status last verified: Mar 2024
First submitted: 12 Oct 2018
Last updated: 27 Mar 2024
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Study at a glance

From the registry record, last updated by the sponsor on 27 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT03727789
Acronym / sponsor ID: I 60017
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
Phase: Phase 1
Study type: Interventional
Recruitment status: TerminatedReason stopped: low accrual
Enrolment: 7 participants (actual)
Lead sponsor: Roswell Park Cancer InstituteUniversity, hospital or other
Collaborators: Incuron
Study start: 1 Jul 2019 (actual)
Primary completion: 16 Jan 2024 (actual)
Study completion: 16 Jan 2024 (actual)
First posted: 1 Nov 2018 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

PRIMARY OBJECTIVES:

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:

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

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:

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 design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Treatment (CBL0137)	Experimental	Drug: FACT Complex-targeting Curaxin CBL0137Patients receive FACT complex-targeting curaxin CBL0137 IA over 15 minutes.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (31 listed)

Patient must have a life expectancy of > 6 months.
Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.
Patients either:
* 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

Key exclusion criteria (21 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
FACT Complex-targeting Curaxin CBL0137Also: CBL0137Given IA	Drug	Treatment (CBL0137)

Primary outcome

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.

8 secondary outcomes

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
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
Incidence of Adverse events
Time frame: At pre- and post-intraarterial infusion assessed up to 24 months
Tumor levels of p53^Ser392 and HSP70 assessed by enzyme-linked immunosorbent assay (ELISA)
Time frame: Up to 24 months

Results and safety

The study was stopped early (reason given: low accrual). Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2024.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Joseph Skitzki principal investigator

Roswell Park Cancer Institute

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 31 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 27 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: low accrual). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome 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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03727789.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Mar 2024; AzTrials last refreshed its copy on 26 Oct 2026.