Neoplasms

Symptoms and General Pathology

All Conditions

Skin and Connective Tissue Diseases

Neoplasm Metastasis

Neoplasms, Second Primary

Skin Neoplasms

Neoplastic Processes

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

0.15% SOR007 (Uncoated Nanoparticle Paclitaxel) Ointment applied topically twice daily for 28 days

1.0% SOR007 (Uncoated Nanoparticle Paclitaxel) Ointment applied topically twice daily for 28 days

2.0% SOR007 (Uncoated Nanoparticle Paclitaxel) Ointment applied topically twice daily for 28 days or up to 56 days

One (1) Finger Tip Unit (FTU), or approximately 0.5 g, of SOR007 ointment will be applied topically to a 50 cm2 treatment area.

SOR007 (Uncoated Nanoparticle Paclitaxel) Ointment

Rose Marie Cavanna-Mast

Julie E Lang, MD

This study evaluates a topical nanoparticle paclitaxel ointment (SOR007) for the treatment of cutaneous metastases from non-melanoma cancer in adults. Three concentrations of SOR007 will be evaluated in dose-rising cohorts of three. An expanded cohort will treat additional subjects at the maximum tolerated dose.

This is a Phase 1/2, open-label, dose-rising study evaluating the safety, tolerability and preliminary efficacy of three concentrations of SOR007 (Uncoated Nanoparticle Paclitaxel) Ointment (0.15%, 1.0%, and 2.0%) applied to non-melanoma cutaneous metastases. A treatment area of 50 cm2 will be selected by the Investigator. Using a gloved hand, subjects will apply one Finger Tip Unit (FTU) of SOR007 to the 50 cm2 treatment area twice daily at approximately the same time each day for 28 days, with the option of extending treatment an additional 28 days to total 56 days for subjects in the dose expansion phase. At each visit (Days 1, 8, 15, 29, and 43 for 28 treatment days; Days 8, 15, 29, 57, and 70 for 56 treatment days), at least two global and two close-up color photographs of the treatment area will be taken (with a ruler for scale). The photographs will be analyzed with ImageJ. Eligible lesions will be determined at baseline by the RECIST definition of measurable tumors (≥ 10mm in its longest diameter). The study will include a dose escalation phase and a dose expansion phase.

In the dose escalation phase, formal safety reviews will be conducted after the last subject in each cohort of three subjects completes 15 days of treatment. The next dose level will enroll upon a finding of safety and tolerability. The top dose or the maximum tolerated dose (if DLT occurs) will be taken into the dose expansion phase and additional subjects will be enrolled to reach a maximum of 16 subjects at that dose.

Phase 1/2, open-label, dose-rising trial of three concentrations of SOR007 (0.15%, 1.0%, 2.0%).

During the dose escalation phase, the study will follow a standard 3+3 dose-ascending design. If a single dose limiting toxicity (DLT) is identified in one of three subjects in the cohort, a further three subjects will be enrolled at the same dose level. If one or more DLT occur in the three additional subjects enrolled in the cohort, dose escalation will stop and the prior dose level will be regarded as the Maximum Tolerated Dose (MTD) and taken forward into the dose expansion phase. If no further DLT are identified, dose escalation will continue, until either a DLT is identified at a higher dose or the top dose of 2% is reached.

In the dose expansion phase, additional subjects will be enrolled up to a maximum of 12 subjects at the dose determined to be the MTD (or the top dose, 2.0% SOR007).

Study of Topical SOR007 Ointment for Cutaneous Metastases

Phase 1/2 Dose-Rising, Safety, Tolerability and Efficacy Study of Topical SOR007 for Cutaneous Metastases

Treatment emergent adverse events will include all reported adverse events, laboratory assessments, physical examination findings, and vital signs.

Objective Clinical Response (Complete Clinical Response (CR) + Partial Response (PR)) is defined as the percentage of study subjects who achieve complete clinical response or partial response 14 days after last treatment (Day 43 or Day 70).

Complete clinical response (CR) is defined as absence of any detectable residual disease in the treatment area; partial response (PR) as at least a 30% decrease in the sum of the diameters of eligible lesion(s) within the treatment area compared to baseline; progressive disease (PD) as at least a 20% increase in the sum of diameters of eligible lesion(s) within the treatment area, taking as reference the smallest sum on study (the sum must also demonstrate an absolute increase of at least 5 mm); and stable disease (SD) as between that defined as PR or PD. Eligible lesions will be determined at baseline by the RECIST definition of measurable tumors (≥ 10mm in its longest diameter).

Change in pain at the treatment area will be measured by the Numeric Rating Scale (NRS-11). The numerical scale ranges from 0 to 10, with 0 being "no pain" and 10 being "the worst pain imaginable." A lower score equates to less severe pain (better outcome) and a higher score equates to more severe pain (worse outcome).

Objective Tumor Response (OTR), defined as the difference in the lesion size within the treatment area between baseline and 14 days after the last dose in the dose group i.e. Day 43 for dose escalation Subjects, and dose expansion Group A Subjects; Day 70 for dose expansion Group B Subjects; or between baseline and last tumor assessment for early terminators. Four OTRs are calculated based on different definitions of "lesion size": 1) Area of the primary eligible lesion, 2) Sum of area of all eligible lesions, 3) Longest diameter of the primary eligible lesion, and 4) Sum of longest diameter of all eligible lesions.

US Biotest, Inc.

NanOlogy, LLC

AEs were collected at all study visits from the time of first study drug application. Study personnel were required to review the Subject's diary at each visit to confirm it was adequately completed and to address and document discrepancies, missing entries and errors. Study personnel also asked open-ended questions to obtain information about AEs at every visit.

0.15% SOR007 (Uncoated Nanoparticle Paclitaxel) Ointment applied topically twice daily for 28 days

SOR007 (Uncoated Nanoparticle Paclitaxel) Ointment: One (1) Finger Tip Unit (FTU), or approximately 0.5 g, of SOR007 ointment will be applied topically to a 50 cm2 treatment area.

SOR007 0.15%

1.0% SOR007 (Uncoated Nanoparticle Paclitaxel) Ointment applied topically twice daily for 28 days

SOR007 (Uncoated Nanoparticle Paclitaxel) Ointment: One (1) Finger Tip Unit (FTU), or approximately 0.5 g, of SOR007 ointment will be applied topically to a 50 cm2 treatment area.

SOR007 1.0%

2.0% SOR007 (Uncoated Nanoparticle Paclitaxel) Ointment applied topically twice daily for 28 days

SOR007 (Uncoated Nanoparticle Paclitaxel) Ointment: One (1) Finger Tip Unit (FTU), or approximately 0.5 g, of SOR007 ointment will be applied topically to a 50 cm2 treatment area.

SOR007 2.0% Group A

2.0% SOR007 (Uncoated Nanoparticle Paclitaxel) Ointment applied topically twice daily for 56 days

SOR007 (Uncoated Nanoparticle Paclitaxel) Ointment: One (1) Finger Tip Unit (FTU), or approximately 0.5 g, of SOR007 ointment will be applied topically to a 50 cm2 treatment area.

SOR007 2.0% Group B

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Body Mass Index

The ECOG performance status scale is a measurement that describes a patient's level of functioning in terms of their ability to care for themselves, daily activity, and physical ability. The scale ranges from 0 to 5, with a lower score indicating a more functional patient and a higher score indicating a patient with more negative impacts to their daily functions.

ECOG Performance Status

All enrolled subjects are included in the baseline analysis population.

Gere diZerega, MD

All subjects who received SOR007 were included in the analysis population.

Incidence of Treatment Emergent Adverse Events

Of the 23 Subjects enrolled, evaluable photography 14 days after the last dose of SOR007 was provided in 14 (60.9%) Subjects; two in the 0.15% treatment group, three in the 1.0% treatment group, four in 2.0% A treatment group, and five in 2.0% B treatment group.

Objective Clinical Response

Baseline (Day 1)

2 Weeks after Last Dose (Day 43 for 28-day treatment groups or Day 70 for 56-day treatment groups)

Change in Pain at the Treatment Area

Based on Area of the Primary Eligible Lesion

Based on Total Area of all Eligible Lesions

Based on Longest Diameter of the Primary Eligible Lesion

Based on Total Longest Diameter of all Eligible Lesions

2.0% SOR007 (Uncoated Nanoparticle Paclitaxel) Ointment applied topically twice daily for 28 days or up to 56 days

SOR007 (Uncoated Nanoparticle Paclitaxel) Ointment: One (1) Finger Tip Unit (FTU), or approximately 0.5 g, of SOR007 ointment will be applied topically to a 50 cm2 treatment area.

SOR007 2.0%

One subject in SOR007 2.0% Group A was not included in the analysis.

Objective Tumor Response (OTR)

Overall Study

Mouth and Tooth Diseases

Infections

Rare Diseases

Carcinoma

Carcinoma, Squamous Cell

Carcinoma, Basal Cell

Sarcoma

Mouth Neoplasms

Soft Tissue Neoplasms

Sarcoma, Kaposi

Head and Neck Neoplasms

Mouth Diseases

Stomatognathic Diseases

Soft Tissue Sarcoma

Oral Cancer

Kaposi Sarcoma

Tongue Cancer

Intratumoral Diffusing alpha-emitters Radiation Therapy (DaRT) Seeds

An intratumoral insertion of a seed(s), loaded with Radium-224, securely fixed in the seeds. The seeds release by recoil into the tumor short-lived alpha-emitting atoms.

Radiation: Diffusing Alpha Radiation Emitters Therapy (DaRT)

Liron Dimnik

Aron Popovtzer, MD

Aron Popovtzer

A unique approach for cancer treatment employing intratumoral diffusing alpha radiation emitter device for superficial cutaneous, mucosal or soft tissue neoplasia

This will be a prospective, open label, single arm, controlled study, assessing the safety and efficacy of diffusing alpha emitters radiation therapy (DaRT) delivered through radioactive seeds inserted into the tumor.

This approach combines the advantages of local intratumoral irradiation of the tumor, as used in conventional brachytherapy, with the power of the alpha radiation emitting atoms, that will be introduced in quantities considerably lower than radiation therapy already used in patients.

Superficial lesions with histopathological confirmation of malignancy will be treated using DaRT seeds.

Reduction in tumor size 70 days after DaRT insertion will be assessed. Safety will be assessed by the incidence, severity and frequency of all Adverse Events (AE).

Alpha Radiation Emitters Device (DaRT) for the Treatment of Cutaneous, Mucosal or Superficial Soft Tissue Neoplasia

A Safety and Effectiveness Study of Intratumoral Diffusing Alpha Radiation Emitters for the Treatment of Malignant Cutaneous, Mucosal or Superficial Soft Tissue Neoplasia

All Adverse Events (AE) related and unrelated to the study treatment

Assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) (Version 1.1)

The incidence, frequency, severity and causality of acute adverse events related to the DaRT treatment according to Common Terminology and Criteria for adverse events (CTCAE) version 5.0.

Assessment by localization of the DaRT seeds in the tumor using CT imaging on the day of DaRT insertion

Assessment of patient reported health-related Quality of Life outcome after DaRT, using QoL questionnaire Skindex-16 questionnaire score

Assessment of patient reported health-related Quality of Life outcome after DaRT, using QoL questionnaire Skin Cancer Index (SCI) questionnaire score

Time elapsed from response to disease progression

Alpha Tau Medical LTD.

Recurrence

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Pembrolizumab

Immunomodulating Agents

Adjuvants, Immunologic

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Intratumoral Diffusing alpha-emitters Radiation Therapy (DaRT) Seeds in Combination with Standard Treatment of Pembrolizumab

Diffusing Alpha Radiation Emitters Therapy (DaRT)

200 mg administered as an intravenous infusion over 30 minutes every 3 weeks

Tami Granot

Iris Gluck, MD

Inbar Finkel, MD

A unique combinational treatment for cancer employing intratumoral diffusing alpha radiation emitter device with check point inhibitor for recurrent unresectable or metastatic Head and Neck Squamous Cell Carcinoma

This will be a prospective, open-label, one arm, single center two-stage adaptive trial designed to stop for either futility or efficacy after the first stage.

This approach will combine Diffusing Alpha Radiation Emitters seeds implantation along with standard treatment of Pembrolizumab for patients with recurrent unresectable or metastatic Head and Neck Squamous Cell Carcinoma (mHNSCC).

The DaRT seeds will be implanted in the target lesion and removed 15-22 days after implantation. Concurrently, patient will receive standard treatment of Pembrolizumab.

Disease evaluation will be assessed by a radiological imaging every 6 weeks starting at day 42 after the DaRT insertion procedure.

A Safety and Efficacy Study for Combinational Treatment of DaRT and Check Point Inhibitor for Recurrent Unresectable or mHNSCC

A Safety and Efficacy Study of Intratumoral Diffusing Alpha Radiation Emitters in Recurrent Unresectable or Metastatic Head and Neck Squamous Cell Carcinoma

This study will assess the change in immune related biomarkers in peripheral blood using Fluorescence-activated cell sorting (FACS) analysis. These biomarkers include: CD3, CD4, CD8, CD69, CD137

Assessed via the Confirmed Best Overall Response (BOR) as defined by Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1)

Assessment of the frequency, severity and causality of acute adverse events related to the DaRT treatment in combination with immune checkpoint inhibitors. This will be assessed and graded according to Common Terminology and Criteria for Adverse Events (CTCAE) version 5.0. (graded 1-5, 1 is mild and 5 is death)

PFS will be defined as time from Pembrolizumab treatment start date to progressive disease according to RECIST v1.1 or death due to any cause, whichever occurs first

Defined as the time from Pembrolizumab treatment start date to death due to any cause or lost to follow up.

Duration of response is defined as the interval from the time measurement criteria are first met for Complete Response (CR), Partial Response (PR), or Stable Disease (SD) (whichever is first recorded) until the first date recurrent or progressive disease is objectively documented.

Adi Cohen

Naama Barel

Aron Popovtzer, M.D

This will be a prospective, open label, single arm, controlled study, assessing the safety and efficacy of re-treatment with diffusing alpha emitters radiation therapy (DaRT) delivered through radioactive seeds inserted into the tumor.

This approach combines the advantages of local intratumoral irradiation of the tumor, as used in conventional brachytherapy, with the power of the alpha radiation emitting atoms, that will be introduced in quantities considerably lower than radiation therapy already used in patients.

Superficial lesions with histopathological confirmation of either recurrent or persistent disease following DaRT treatment. .

Reduction in tumor size 70 days after DaRT insertion will be assessed. Safety will be assessed by the incidence, severity and frequency of all Adverse Events (AE).

Retreatment With Intratumoral Diffusing Alpha Radiation Emitters

A Safety and Efficacy Study of Retreatment With Intratumoral Diffusing Alpha Radiation Emitters

Incidence of all Adverse Events (AE) related and unrelated to the study treatment.

Frequency, severity and causality of acute adverse events related to the DaRT treatment. Adverse events will be assessed and graded according to Common Terminology and Criteria for adverse events (CTCAE) version 5.0.

Will be assessed as the number of complete responses, partial responses and stable disease divided by the total numbers of tumors treated.

Immune System Diseases

Melanoma

Hypersensitivity

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Neuroendocrine Tumor

Neuroepithelioma

This research program is in keeping with the chemistry/biology/clinical interface and gathers 4 teams with complementary expertise in these respective fields. It will allow deciphering the mechanism(s) of action of new Thiazole-Benzenesulfonamide family (TZB) derivatives on metastatic melanoma sensitive and resistant to BRAF and MEK inhibitors. Investigators will use melanoma cell lines and primary cells from patients to validate these compounds in collaboration with clinical team 2 and 4. In conclusion, the investigators expect to establish the proof of concept that this new class of bioactive molecules (first in class) we developed in collaboration with Team 3 have the potential to go to the clinic for the treatment of highly aggressive cancers and particularly metastatic melanoma sensitive and resistant B-Raf and MEK inhibitors. Furthermore, the realization of this project can undoubtedly increase the knowledge of mechanisms and signaling pathways that are involved in resistant to BRAF and MEK inhibitors, and allow the selection of drug candidates capable of restoring the sensitivity of these melanoma cells.

biopsy of a target lesion (skin, lymph node or visceral metastases)

Preclinical Validation of New Anti-melanoma Compounds

Preclinical Validation of New Anti-melanoma Compounds: Study on Patient Melanoma Cells Sensitive and Resistant to BRAF/MEK Inhibitors

The status of the BRAF mutation will be expressed through laboratory analysis of the samples collected, i.e. positive or negative.

Centre Hospitalier Universitaire de Nice

Tomer Charas, MD

Alpha Radiation Emitters Device (DaRT) for the Treatment of Cutaneous, Mucosal or Superficial Soft Tissue Neoplasia.

Assessment of the rate of malignant cutaneous, mucosal or superficial soft tissue tumors response using the Response Evaluation Criteria in Solid Tumors (RECIST) (Version 1.1)

The incidence, frequency, severity and causality of acute adverse events related to the DaRT treatment

Assessment of the reduction in tumor volume based on CT / PET-CT measured tumor volume

Assessment of the DaRT seeds placement by localization of the DaRT seeds in the tumor using CT imaging on the day of DaRT insertion.

Assessment of patient reported health-related Quality of Life outcome after DaRT, using QoL questionnaire Skindex-16 questionnaire score. An overall score ranging from 0 (best) to 100 (worst).

Assessment of patient reported health-related Quality of Life outcome after DaRT, using QoL questionnaire Skin Cancer Index (SCI) questionnaire score. An overall score ranging from 0 (best) to 100 (worst).

Device: Radiation: Diffusing Alpha Radiation Emitters Therapy (DaRT)

Laura Eibenschuz, MD

This will be a prospective, open label, single arm, controlled study, assessing the safety and efficacy of diffusing alpha emitters radiation therapy (DaRT) delivered through radioactive seeds inserted into the tumor.

This approach combines the advantages of local intratumoral irradiation of the tumor, as used in conventional brachytherapy, with the power of the alpha radiation emitting atoms, that will be introduced in quantities considerably lower than radiation therapy already used in patients.

Superficial lesions with histopathological confirmation of malignancy will be treated using DaRT seeds.

Reduction in tumor volume and evaluation the percent of necrotic tissue in the tumor 30-45 days after DaRT seeds insertion (15-30 days after seed removal) will be assessed. Safety will be assessed by the cumulative incidence, worst severity and frequency of adverse events (AEs) observed including the follow-up period.

Alpha Radiation Emitters Device for the Treatment of Cutaneous, Mucosal and Superficial Soft Tissue Neoplasia (DaRT)

A Safety and Preliminary Effectiveness Study of Intratumoral Diffusing Alpha Radiation Emitters on Cutaneous, Mucosal and Superficial Soft Tissue Neoplasia

Evaluate the effectiveness of the DaRT treatment, in terms of percent of necrotic tissue present in the remaining tumor tissue surgically removed 15-30 days after removal of DaRT seeds.

The study primary objective is to evaluate the safety of the DaRT treatment in terms of incidence of device related Serious Adverse Events (SAE).

Evaluation on the effectiveness of the DaRT treatment, in terms of tumor volume reduction.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Topical SOR007 Ointment for Cutaneous Metastases	NCT03101358	Cutaneous Metas...	SOR007 (Uncoate...	18 Years -	NanOlogy, LLC
Study of Topical SOR007 Ointment for Cutaneous Metastases	NCT03101358	Cutaneous Metas...	SOR007 (Uncoate...	18 Years -	NanOlogy, LLC
Alpha Radiation Emitters Device (DaRT) for the Treatment of Cutaneous, Mucosal or Superficial Soft Tissue Neoplasia	NCT04534127	Skin Cancer Mucosal Neoplas... Soft Tissue Neo...	Radiation: Diff...	18 Years -	Alpha Tau Medical LTD.
A Safety and Efficacy Study for Combinational Treatment of DaRT and Check Point Inhibitor for Recurrent Unresectable or mHNSCC	NCT05047094	Head and Neck S... Skin Cancer Metastatic Head...	Diffusing Alpha... Pembrolizumab	18 Years -	Alpha Tau Medical LTD.
Retreatment With Intratumoral Diffusing Alpha Radiation Emitters	NCT04540588	Skin Cancer Mucosal Neoplas... Soft Tissue Neo...	Radiation: Diff...	18 Years -	Alpha Tau Medical LTD.
Preclinical Validation of New Anti-melanoma Compounds	NCT03798977	Melanoma		18 Years -	Centre Hospitalier Universitaire de Nice
Alpha Radiation Emitters Device (DaRT) for the Treatment of Cutaneous, Mucosal or Superficial Soft Tissue Neoplasia.	NCT03889899	Skin Cancer Mucosal Neoplas... Soft Tissue Neo...	Radiation: Diff...	18 Years -	Alpha Tau Medical LTD.
Alpha Radiation Emitters Device for the Treatment of Cutaneous, Mucosal and Superficial Soft Tissue Neoplasia (DaRT)	NCT03886181	Skin Cancer Mucosal Neoplas... Soft Tissue Neo...	Device: Radiati...	18 Years -	Alpha Tau Medical LTD.
Alpha Radiation Emitters Device for the Treatment of Cutaneous, Mucosal and Superficial Soft Tissue Neoplasia (DaRT)	NCT03886181	Skin Cancer Mucosal Neoplas... Soft Tissue Neo...	Device: Radiati...	18 Years -	Alpha Tau Medical LTD.
Alpha Radiation Emitters Device for the Treatment of Cutaneous, Mucosal or Superficial Soft Tissue Neoplasia (DaRT)	NCT03737734	Skin Cancer Mucosal Neoplas... Soft Tissue Neo...	Radiation: Diff...	18 Years -	Alpha Tau Medical LTD.
Alpha Radiation Emitters Device (DaRT) for the Treatment of Cutaneous, Mucosal or Superficial Soft Tissue Neoplasia.	NCT03889899	Skin Cancer Mucosal Neoplas... Soft Tissue Neo...	Radiation: Diff...	18 Years -	Alpha Tau Medical LTD.

Spots Global Cancer Trial Database for skin metastasis