Symptoms and General Pathology

All Conditions

Neoplasms

Skin and Connective Tissue Diseases

Rare Diseases

Recurrence

Melanoma

Sarcoma

Melanoma, Cutaneous Malignant

Skin Neoplasms

Disease Attributes

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Diseases

Neoplasms, Connective and Soft Tissue

Soft Tissue Sarcoma

Neuroendocrine Tumor

Neuroepithelioma

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

FACT Complex-targeting Curaxin CBL0137

Joseph Skitzki

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.

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.

CBL0137 in Treating Patients With Advanced Extremity Melanoma or Sarcoma

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

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.

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.

Responses will be tabulated, and complete response rate will be estimated with its exact 80% confidence interval.

Changes in clinical laboratory values while receiving CBL0137

Incuron

Roswell Park Cancer Institute

Behaviors and Mental Disorders

Histiocytoma, Malignant Fibrous

Aggression

Histiocytoma

Neoplasms, Fibrous Tissue

Neoplasms, Connective Tissue

Undifferentiated Pleomorphic Sarcoma

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Pembrolizumab

Doxorubicin

Liposomal doxorubicin

Daunorubicin

Immunomodulating Agents

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Patients receive doxorubicin IV over 3-10 minutes or up to 3 hours on day 1 of each cycle. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo ECHO or MUGA scan during screening, as well as standard imaging scans and blood sample collection throughout the study.

Patients receive doxorubicin IV over 3-10 minutes or up to 3 hours on day 1 of each cycle. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. At time of disease progression, patients may begin receiving pembrolizumab alone IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of additional progression or unacceptable toxicity. Patients also undergo ECHO or MUGA scan during screening, as well as standard imaging scans and blood sample collection throughout the study.

Biospecimen Collection

Diagnostic Imaging

Echocardiography

Multigated Acquisition Scan

Seth M Pollack

This phase II trial compares the effect of immunotherapy (pembrolizumab) plus chemotherapy (doxorubicin) to chemotherapy (doxorubicin) alone in treating patients with undifferentiated pleomorphic sarcoma (UPS) or a related poorly differentiated sarcoma that has spread from where it first started to other places in the body (metastatic) or that cannot be removed by surgery (unresectable). Doxorubicin is in a class of medications called anthracyclines. Doxorubicin damages the cell's DNA and may kill tumor cells. It also blocks a certain enzyme needed for cell division and DNA repair. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Adding immunotherapy (pembrolizumab) to the standard chemotherapy (doxorubicin) may help patients with metastatic or unresectable UPS or a related poorly differentiated sarcoma live longer without having disease progression.

PRIMARY OBJECTIVE:

I. To assess whether the combination of doxorubicin and pembrolizumab will improve progression free survival (PFS) in UPS and related poorly differentiated sarcomas relative to doxorubicin alone.

KEY SECONDARY OBJECTIVE:

I. To assess whether the combination of doxorubicin and pembrolizumab versus (vs) the re-introduction of pembrolizumab in the doxorubicin alone arm at disease progression (i.e., upfront pembrolizumab vs second line pembrolizumab) improves overall survival (OS).

SECONDARY OBJECTIVES:

I. To evaluate the safety and tolerability in each treatment arm. II. To quantify overall response rate (ORR) and durability of response (DOR) in each treatment.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive doxorubicin intravenously (IV) over 3-10 minutes or up to 3 hours on day 1 of each cycle. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive doxorubicin IV over 3-10 minutes or up to 3 hours on day 1 of each cycle. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. At time of disease progression, patients may begin receiving pembrolizumab alone IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of additional progression or unacceptable toxicity.

Patients in both arms also undergo echocardiogram (ECHO) or multigated acquisition (MUGA) scan during screening, as well as standard imaging scans and blood sample collection throughout the study.

After completion of study treatment, patients are followed up periodically for up to 5 years.

Measuring if Immunotherapy Plus Chemotherapy is Better Than Chemotherapy Alone for Patients With Aggressive Poorly Differentiated Sarcomas

A Randomized Phase II Trial of Doxorubicin + Pembrolizumab Versus Doxorubicin Alone for the Treatment of Undifferentiated Pleomorphic Sarcoma (UPS) and Related Poorly Differentiated Sarcomas

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Will be compared between the treatment arms (doxorubicin + pembrolizumab versus \[vs\] doxorubicin alone). The comparison of PFS between treatment arms will be done using a stratified (on Eastern Cooperative Oncology group \[ECOG\] performance status \[0 vs 1\]) log-rank test with a 5% type I error (1-sided).

Will be compared between doxorubicin + pembrolizumab vs doxorubicin alone to test the strategy of upfront pembrolizumab vs second line pembrolizumab.

National Cancer Institute (NCI)

Liposarcoma

Neoplasms, Adipose Tissue

Antibodies

Cemiplimab

Immunoglobulins

Immunoglobulin G

Palbociclib

Immunoglobulins, Intravenous

Immunologic Factors

Protein Kinase Inhibitors

Patients receive palbociclib PO on study. Patients will be allowed to cross over to Arm II following documentation of disease progression. Patients undergo MRI or CT scans throughout the trial. Patients may also undergo blood sample collection on study.

Patients receive palbociclib PO and cemiplimab IV on study. Patients undergo MRI or a CT scan throughout the trial. Patients may also undergo blood sample collection on study.

Magnetic Resonance Imaging

Computed Tomography

Biospecimen collection

Questionnaire Administration

Matthew Ingham, MD

Beth Smith

Site Public Contact

Vanessa Eulo

Shahzad Siddique

Steven I. Robinson

Tatjana Kolevska

Sosipatros A. Boikos

Tanmay Sahai

Bryan A. Faller

Pedro Viveiros

Bruce E. Brockstein

This phase II trial compares the effect of treatment with palbociclib alone to treatment with palbociclib plus cemiplimab for treating patients with dedifferentiated liposarcoma that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Palbociclib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Cemiplimab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. The combination of these two drugs may be more effective in shrinking or stabilizing advanced dedifferentiated liposarcoma compared to palbociclib alone.

PRIMARY OBJECTIVES:

I. To perform a safety lead-in among 6 patients to confirm that the combination of palbociclib and cemiplimab is safe and tolerable.

II. To evaluate whether palbociclib in combination with cemiplimab (Arm 2) demonstrates a superior progression-free survival (PFS) compared to palbociclib monotherapy (Arm 1) for patients with advanced dedifferentiated liposarcoma (DDLPS).

SECONDARY OBJECTIVES:

I. To evaluate the toxicity profile in and across each treatment arm as determined by both Common Terminology Criteria for Adverse Events (CTCAE) and Patient Reported Outcomes (PRO)-CTCAE criteria.

II. To evaluate and compare the objective response rate (ORR) and duration of response (DOR) in and across each treatment arm.

III. To evaluate and compare the overall survival (OS) in and across each treatment arm.

IV. To evaluate and compare progression-free rate at 8 weeks (PFR8) in and across each treatment arm.

EXPLORATORY OBJECTIVES:

I. To collect genomic sequencing data previously collected as standard of care, including data on CDK4 copy number (as determined by fluorescence in situ hybridization \[FISH\] or other molecular testing).

II. To conduct multiplex immunohistochemistry using archival tumor tissue (where available) to define densities of infiltrating immune cell subsets and tumor and immune cell major histocompatibility complex (MHC) and PD-L1 expression.

III. To perform an exploratory analysis to evaluate for any relationship between CDK4 copy number and (a) the tumor immune microenvironment as defined by multiplex immunohistochemistry and (b) clinical outcomes from study treatment.

IV. To explore efficacy and toxicity endpoints, including PFS and ORR, for patients who progress on palbociclib monotherapy and crossover to the palbociclib plus cemiplimab combination.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive palbociclib orally (PO) on study. Patients will be allowed to cross over to Arm II following documentation of disease progression. Patients undergo magnetic resonance imaging (MRI) or computed tomography (CT) scans throughout the trial. Patients may also undergo blood sample collection on study.

ARM II: Patients receive palbociclib PO and cemiplimab intravenously (IV) on study. Patients undergo MRI or CT scans throughout the trial. Patients may also undergo blood sample collection on study.

Testing the Addition of Cemiplimab to Palbociclib for the Treatment of Advanced Dedifferentiated Liposarcoma

Official Title A Randomized Phase 2 Trial With a Safety Lead-In to Evaluate Palbociclib Versus Palbociclib and Cemiplimab for the Treatment of Advanced Dedifferentiated Liposarcoma

Explore data on CDK4 copy number (by fluorescence in situ hybridization \[FISH\] or other molecular testing) through plots and summary statistics.

Conduct multiplex immunohistochemistry using archival tumor tissue (where available) to summarize densities of infiltrating immune cell subsets and tumor and immune cell MHC and PD-L1 expression.

Explore the relationship between CDK4 copy number and (a) the tumor immune microenvironment as defined by multiplex immunohistochemistry and (b) clinical outcomes from study treatment Clinical endpoints include PFS, objective response rate, OS, PFR8, and DoR. Cox regression will be used on time-to-event outcomes and T-test on binary outcomes

Explore the efficacy and toxicity endpoints for patients who progress on palbociclib monotherapy and crossover to the palbociclib plus cemiplimab combination A sensitivity analysis will be conducted to see how crossover effects overall survival. Rate and severity of adverse events will be used to assess differences between crossover and non-crossover patients.

Efficacy analyses will be based on intention to treat principles. PFS will be compared between the two treatment arms using Kaplan-Meier methods. The hazard ratio, median PFS, and estimated PFS rates at 12, 24, 36, and 48 months will be estimated along with corresponding 95% confidence intervals. A log-rank test will be used to compare the PFS distributions between the two treatment arms in this cohort. Cox proportional hazards models will also be used to assess the impact of treatment arm on PFS when stratifying on the stratification factors.

Patients will be evaluated for adverse events using the National Cancer Institute Common Toxicity Criteria for Adverse Events version 5.0. Summary statistics (e.g., mean, median, standard deviation) and frequency tables will be used to describe the distributions of adverse events. Rates of adverse events occurring in the treatment arm will be compared to the control arm with chi-squared tests (or suitable alternative) used for comparisons where applicable. Tolerability will also be evaluated, summarizing rates of dose delays or modifications, reasons patients end treatment, and time to end of active treatment.

Defined for all evaluable patients who have achieved an objective response as the date at which the patient's earliest best objective status is first noted to be either a complete response or partial response to the earliest date progression is documented, or death if no prior evidence of disease progression. The distribution of DoR will be estimated using the method of Kaplan-Meier.

Defined as the time from randomization to death due to any cause. Patients who are alive will be censored at last follow-up for OS. The distribution of survival time will be estimated using the method of Kaplan-Meier. OS will be compared between treatment arms using the log-rank test. OS medians, survival rates and hazard ratio will be estimated along with 95% confidence intervals.

Defined as the proportion of evaluable patients who are alive and without evidence of disease progression 8 weeks after initiation of study therapy. The final PFR8 point estimate and corresponding 95% confidence interval calculated using Clopper-Pearson method.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
CBL0137 in Treating Patients With Advanced Extremity Melanoma or Sarcoma	NCT03727789	Advanced Cutane... Advanced Sarcom... Clinical Stage ... Clinical Stage ... Pathologic Stag... Pathologic Stag... Pathologic Stag... Recurrent Cutan... Recurrent Sarco... Stage III Soft ... Stage IIIA Soft... Stage IIIB Soft... Stage IV Soft T...	FACT Complex-ta...	18 Years -	Roswell Park Cancer Institute
Measuring if Immunotherapy Plus Chemotherapy is Better Than Chemotherapy Alone for Patients With Aggressive Poorly Differentiated Sarcomas	NCT06422806	Stage III Soft ... Stage IV Soft T... Undifferentiate...	Biospecimen Col... Diagnostic Imag... Doxorubicin Echocardiograph... Multigated Acqu... Pembrolizumab	18 Years -	National Cancer Institute (NCI)
Measuring if Immunotherapy Plus Chemotherapy is Better Than Chemotherapy Alone for Patients With Aggressive Poorly Differentiated Sarcomas	NCT06422806	Stage III Soft ... Stage IV Soft T... Undifferentiate...	Biospecimen Col... Diagnostic Imag... Doxorubicin Echocardiograph... Multigated Acqu... Pembrolizumab	18 Years -	National Cancer Institute (NCI)
Testing the Addition of Cemiplimab to Palbociclib for the Treatment of Advanced Dedifferentiated Liposarcoma	NCT05694871	Advanced Dediff... Locally Advance... Metastatic Dedi... Stage III Soft ... Stage IV Soft T... Unresectable De...	Palbociclib Cemiplimab Magnetic Resona... Computed Tomogr... Biospecimen col... Questionnaire A...	18 Years -	Alliance for Clinical Trials in Oncology
CBL0137 in Treating Patients With Advanced Extremity Melanoma or Sarcoma	NCT03727789	Advanced Cutane... Advanced Sarcom... Clinical Stage ... Clinical Stage ... Pathologic Stag... Pathologic Stag... Pathologic Stag... Recurrent Cutan... Recurrent Sarco... Stage III Soft ... Stage IIIA Soft... Stage IIIB Soft... Stage IV Soft T...	FACT Complex-ta...	18 Years -	Roswell Park Cancer Institute

Spots Global Cancer Trial Database for stage iv soft tissue sarcoma of the trunk and extremities ajcc v8