Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Eye Diseases

Rare Diseases

Melanoma

Uveal Neoplasms

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 Neoplasms

Skin Diseases

Eye Neoplasms

Uveal Diseases

Intraocular Melanoma

Neuroendocrine Tumor

Neuroepithelioma

All Drugs and Chemicals

Entrectinib

Protein Kinase Inhibitors

Enzyme Inhibitors

Phase 1b will determine the MTD of PAC-1 in combination with entrectinib. Study treatment will include: PAC-1 will be taken orally on Days 1-21 and Entrectinib will be taken orally on Days 1-28 of each 28-day cycle. Treatment will continue until disease progression (based on RECIST 1.1 criteria), unacceptable toxicity, subject withdrawal of informed consent, or subject death either from progression of disease, the therapy itself, or from other causes.

Pharmacokinetic (PK) and pharmacodynamic (PD) assay for PAC-1 will be performed during Days 1 and 21 of Cycle 1. PAC-1 will be given on Day 1 of Cycle 1, withheld on Day 2 and Day 3 of Cycle 1 then reinitiated on Day 4 of Cycle 1 to continue for 21 days of the 28-day cycle. For each successive cycle, PAC-1 therapy will be initiated on Day 1 and continue for 21 days of the 28-day cycle.

PAC-1

Pharmacokinetic and pharmacodynamic assay for entrectinib will be performed during Days 3 and 21 of Cycle 1. Entrectinib therapy will be withheld on Day 1 and Day 2 of Cycle 1, initiated on Day 3 of Cycle 1 and continue for the remainder of the 28 day cycle. For each successive cycle, entrectinib will be intiated on Day 1 and continue for 28 days of the 28-day cycle.

Arkadiusz Dudek, MD, PhD

Single arm study with dose escalation Phase Ib cohort followed by a Phase II cohort. PAC-1 (PO) will be given daily on Days 1 through 21 of each cycle (28-day cycle). Entrectinib (PO) will be given daily on Days 1 through 28 of each cycle. Response will be evaluated after every 2 cycles. Treatment will continue until disease progression based on RECIST criteria or intolerable toxicity.

Study of PAC-1 and Entrectinib for Patients With Metastatic Uveal Melanoma

Phase 1B/2 Study of PAC-1 and Entrectinib for Patients With Metastatic Uveal Melanoma

The MTD of PAC-1 in combination with entrectinib is the highest tested dose of PAC-1 combined with entrectinib with DLT rate of less than 33% in first cycle of therapy (i.e., ≤1 out of 6 subjects with DLT)

PFS is defined as proportion of alive subjects with metastatic uveal melanoma at 3 months from treatment initiation with PAC-1 in combination with entrectinib without evidence of radiological disease progression by RECIST 1.1.

The frequency and severity of all treatment related grade 1 and 2 adverse events are reported by CTCAEv5 term and grade.

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD.

ORR is defined as the proportion of all subjects with confirmed PR or CR according to RECIST 1.1.

DoR is defined as the time that measurement criteria are met for complete or partial response (whichever status is recorded first) until the date that recurrent or progressive disease is objectively documented

OS is defined as the time from treatment initiation with PAC-1 in combination with entrectinib until death as a result of any cause

HealthPartners Regions Cancer Care and Frauenshuh Cancer Care Centers

Vanquish Oncology, Inc.

Genentech, Inc.

Midwest Melanoma Partnership

Arkadiusz Z. Dudek, MD

Sponsor-Investigator

Phase 1b will determine the MTD of PAC-1 in combination with entrectinib. Study treatment will include: PAC-1 will be taken orally on Days 1-21 and Entrectinib will be taken orally on Days 1-28 of each 28-day cycle. Treatment will continue until disease progression (based on RECIST 1.1 criteria), unacceptable toxicity, subject withdrawal of informed consent, or subject death either from progression of disease, the therapy itself, or from other causes.

PAC-1: Pharmacokinetic (PK) and pharmacodynamic (PD) assay for PAC-1 will be performed during Days 1 and 21 of Cycle 1. PAC-1 will be given on Day 1 of Cycle 1, withheld on Day 2 and Day 3 of Cycle 1 then reinitiated on Day 4 of Cycle 1 to continue for 21 days of the 28-day cycle. For each successive cycle, PAC-1 therapy will be initiated on Day 1 and continue for 21 days of the 28-day cycle.

Entrectinib: Pharmacokinetic and pharmacodynamic assay for entrectinib will be performed during Days 3 and 21 of Cycle 1. Entrectinib therapy will be withheld on Day 1 and Day 2 of Cycle 1, initiated on Day 3 of Cycle 1 and continue for the remainder of the 28 day cycle. For each successive cycle, entrectinib will be intiated on Day 1 and continue for 28 days of the 28-day cycle.

Study Treatment Arm

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Fauzia Sharmin

PAC-1(Dose level 1)

Entrectinib(Dose level 1)

Because of episodes of neutropenia in two patients and grade 2 dizziness and ataxia in two patients after the first cycle of therapy, dose interruptions and reductions to a lower dose level (Dose level -1: 625 mg PAC-1 + 400 mg Entrectinib) were required. The new dose level (Dose level -1) was not further explored due to lack of funding. Therefore, the study did not determine an MTD.

Phase 1b: Determine Maximum Tolerated Dose (MTD)

This study is terminated at phase 1b without reaching MTD due to lack of funding. Therefore, there is no accrual in phase 2.

Phase 2: Progression Free Survival at 3 Months

Dizziness

Dysarthria

Anemia

Increased creatinine

Fatigue

Ataxia

Dysgeusia

Neutropenia

AST elevation

Face edema

Constipation

Skin pain

ALT elevation

Flashing lights

Eye Floaters

Tinnitus

Akathisia

Dyspepsia

Nausea

Abdominal pain

Urinary incontinence

Urinary hesitancy

Euphoria

Memory impairment

Numbness

Back pain

Edema limbs

Sensory neuropathy

Macular rash

Thrombocytopenia

Presyncope

Mental fog

This study is terminated at phase 1b due to lack of funding. Therefore, no accrual in phase 2.

Assess Adverse Events

This study is terminated at phase 1b without reaching MTD due to lack of funding. Therefore, no accrual in phase 2 and no result available for ORR.

Phase 2: Overall Response Rate (ORR)

This study is terminated at phase 1b due to lack of funding. Therefore, no accrual in phase 2 and no result for DoR.

Spots Global Cancer Trial Database for Study of PAC-1 and Entrectinib for Patients With Metastatic Uveal Melanoma

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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