Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Rare Diseases

Sarcoma

Sarcoma, Synovial

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Neoplasms, Connective Tissue

Soft Tissue Sarcoma

Synovial Sarcoma

All Drugs and Chemicals

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Micronutrients

Bone Density Conservation Agents

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Edetic Acid

Pentetic Acid

Antidotes

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Iron

Iron Chelating Agents

Calcium

Calcium, Dietary

1.5 mg of OTSA101-DTPA radiolabelled with 370MBq of 90Y

1.5 mg of OTSA101-DTPA radiolabelled with 1110 MBq of 90Y

3 mg of OTSA101-DTPA radiolabelled with 2220 MBq of 90Y

Part 2 of the study 1.5 mg of OTSA101-DTPA radiolabelled with 370MBq of 90Y will be administered IV as a single injection on Day 0.

OTSA101-DTPA-90Y level 1

Part 2 of the study 1.5 mg of OTSA101-DTPA radiolabelled with 1110 MBq of 90Y will be administered IV as a single injection on Day 0.

OTSA101-DTPA-90Y level 2

Part 2 of the study 3 mg of OTSA101-DTPA radiolabelled with 2220 MBq of 90Y will be administered IV as a single injection on Day 0.

This third dose level evaluation will be based on safety and preliminary efficacy data.

OTSA101-DTPA-90Y level 3

Jean-Yves BLAY, MD, PhD

Advanced synovial sarcoma represents an unmet medical need. The gene encoding frizzled homologue 10 (FZD10), a 7-transmenbrane receptor, member of the Wnt signalling receptor family, is overexpressed in SS and is undetectable in normal human tissues except placenta.

OncoTherapy Science Inc. has developed a chimeric humanized monoclonal antibody (mAb) against FZD10, named OTSA101. Non-radiolabeled OTSA101 antibody has only weak antagonistic activity on SS cell growth. However, Yttrium 90-radiolabeled OTSA101 (OTSA101-DTPA-90Y) showed significant antitumor activity following a single intravenous injection in mouse xenograft model.

This first in man clinical trial (Phase I) in relapsing SS patients resistant to Doxorubicin and ifosfamide will be divided in 2 parts.

In Part 1 (imaging part using OTSA101 radiolabelled with Indium 111 \[111In\]), the biodistribution and tumor uptake of OTSA101-DTPA-111In will be followed using 111In as radiotracer.

In Part 2 (therapeutic part with OTSA101 radiolabelled with Yttrium 90 \[90Y\]), the safety and PK profiles of OTSA101-DTPA-90Y will be determined and preliminary efficacy data will be collected.

This first in Man study should allow defining the optimal recommended dose of OTSA101-DTPA-90Y.

Patients will be followed during 1 year.

PART 1: Imaging with OTSA101 DTPA-111In OTSA101-DTPA-111In (1.5mg OTSA101-DTPA radiolabeled with 185 MBq of 11In) will be administered intravenously (IV) as a single injection on Day -28 (D-28). Patients will undergo serial anterior-posterior gamma scans and single photon emission computed tomography (SPECT/CT) at 1, 5, 24, 48, 72, 144 hours post-dosing to estimate absorbed radiation doses to tumor, to normal organs (i.e., liver, lung, kidney, and bone marrow), and whole body in order to determine OTSA101-DTPA-111In tumor uptake (ID%/g \[% of injected dose (ID) per gram of tumor\]) and biodistribution (ratio tumor/normal tissue of estimated radiation-absorbed dose). PK sampling will be performed at the same time points with additional sampling at D-14 and D0.

A Steering Committee meeting is planned at the end of PART 1 for each patient. The Steering Committee will evaluate on a case by case basis at Day -7 for each patient if he/she can proceed to the therapeutic part based on tumor targeting, biodistribution, safety and clinical assessments:

* Patients with expected biodistribution and tumor uptake, no safety concerns and no overt signs of disease progression will proceed to the therapeutic part of the study after validation by the Steering Committee.
* Patients displaying abnormal/unexpected biodistribution of OTSA101-DTPA-111In, safety concerns and/or overt sign of disease progression will be taken off the study and other therapeutic plan will be envisaged.

PART 2: Therapeutic dose of OTSA101-DTPA-90Y OTSA101-DTPA-90Y will be administered IV as a single injection on Day 0 (i.e. 14 days after the injection of OTSA101-DTPA-111In - A 1week-delay \[i.e. +7 days\] is authorized from the planned D0).

Twelve (12) patients should be randomized in the PART 2 and treated with OTSA101-DTPA-90Y at two initial dose levels (6 patients per dose level):

* Arm A: 1.5 mg of OTSA101-DTPA radiolabeled with 370MBq of 90Y (Dose level 1 (DL1)
* Arm B: 1.5 mg of OTSA101-DTPA radiolabeled with 1110 MBq of 90Y (Dose level 2 (DL2)

Based on safety and preliminary efficacy data, a third dose level will be evaluated in 6 additional patients:

* Arm C: 3 mg of OTSA101-DTPA radiolabeled with 2220 MBq of 90Y (Dose level 3 (DL3).

Such a study design will allow the determination of an optimal and recommended dose, surrounded by a lower suboptimal dose and a higher maximal tolerated (or possibly toxic) dose.

The first 3 patients will be enrolled at Centre Léon Bérard. Following the randomization of the first 2 patients, the accrual will be stopped for a maximal period of 1 month. The safety data will be reviewed every 2 randomized patients. Thee benefit/risk ratio will be regularly reviewed by the iDSMB and the Steering Committee (See Section Study Committee).

A compassionate program is planned for all randomized patients who derive clinical benefit from the study drug (at least stable disease and acceptable tolerance). A maximum of 4 injections per year will be planned. Subsequent injection will be performed provided that the eligibility criteria (except criteria related to previous treatment) are met before the day of administration. All inclusion in the compassionate program will be validated by the Steering Committee.

First in Man Study Investigating the Biodistribution, the Safety and Optimal Recommended Dose of a New Radiolabelled Monoclonal Antibody Targeting Frizzled Homolog 10

First in Man Study Investigating the Biodistribution, the Safety and Optimal Recommended Dose of a New Radiolabelled Monoclonal Antibody Targeting Frizzled Homolog 10 (FZD10) in Patients With Relapsed or Refractory Non Resectable Synovial Sarcomas

Limiting Event is defined as unacceptable/unexpected biodistribution/binding of the mAb, and/or absence of tumor uptake. Data review will be performed on a patient per patient basis. The Biodistribution and binding of OTSA101-DTPA-111In will be analyzed. The rate of Limiting Event will be summarized by a proportion together with its 95% confidence interval.

The safety profile will be summarized with descriptive statistics including the following:

* Occurrence of Severe Toxicities during the first 8 weeks post-injection of OTSA101-DTPA-90Y.
* Occurrence of adverse events and serious adverse events during the study treatment period, including laboratory abnormalities, according to CTCAE v4.0 criteria.
* Optimal recommended dose, defined as the dose level of OTSA101-DTPA-90Y with the best benefice-risk ratio taking into account the preliminary efficacy and safety data.

The following PK parameters will be collected: Cmax, tmax, t½: terminal half-life; AUC, Cl, Vss: Volume of distribution. These PK parameters will be calculated using non-compartmental analysis.

The safety profile of OTSA101-DTPA-111In will be summarized with descriptive statistics. The occurrence of adverse events and serious adverse events during the whole imaging part, including laboratory abnormalities, will be summarized by a proportion together with its 95% confidence interval.

The overall response rate is defined as the proportion of patients with a complete response or partial response on target lesions according to RECIST 1.1 criteria.

The clinical benefit rate is defined as the proportion of patients with a complete response or partial response or a stable disease on target lesions according to RECIST 1.1 criteria.

The duration of clinical response, measured from the time of first documented response until the first documented disease progression or death due to underlying cancer, will be described in responding subjects using descriptive statistics.

The following parameters will be collected: Cmax, tmax, t½: terminal half-life; AUC, Cl, Vss: Volume of distribution. Pharmacokinetics will be presented as descriptive statistics. Dose proportionality will be evaluated when applicable by an ANOVA mixed model. Accumulation will be assessed by Wilcoxon signed rank test.

OncoTherapy Science, Inc.

Centre Leon Berard

Respiratory Tract (Lung and Bronchial) Diseases

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Neoplasm Metastasis

Breast Neoplasms

Triple Negative Breast Neoplasms

Ovarian Neoplasms

Melanoma

Carcinoma, Transitional Cell

Neuroblastoma

Neoplasms, Second Primary

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Skin Diseases

Breast Diseases

Neuroectodermal Tumors, Primitive, Peripheral

Neoplasms, Neuroepithelial

Neoplasms, Glandular and Epithelial

Neoplastic Processes

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Ovarian Cancer

Transitional Cell Carcinoma

Neuroepithelioma

Antineoplastic Agents

Antirheumatic Agents

Anti-Infective Agents

Analgesics

Cyclophosphamide

Aldesleukin

Interleukin-2

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Analgesics, Non-Narcotic

Anti-HIV Agents

Anti-Retroviral Agents

Antiviral Agents

This is a two-part, non-randomized, open label, single-site Phase I/II study. The first Part A is a dose ranging maximum tolerated dose (MTD) study and Part B is an extension phase to evaluate safety at the selected safe dose. A Data Safety Monitoring Board (DSMB) will determine the safe dose for testing in the expansion phase (Part B).

Part A will be according to a 3+3 dose escalation design. A total of up to 20 patients will participate in this Part.

Part B will be an expansion phase. The objective will be to determine if the treatment regimen is associated with a clinical response rate that can rule out 5% (p0=0.05) in favor of a modest 20% Partial Response (PR) + Complete Response (CR) rate (p1=0.20).

A total of up to 43 patients may be enrolled in Part B (41 +2, allowing for up to 2 non-evaluable patients).

1. CYCLOPHOSPHAMIDE 250 mg/msq, Day -5,-4,-3 with FLUDARABIN 25 mg/msq, Day -5,-4,-3

CYCLOPHOSPHAMIDE and FLUDARABIN

CYCLOPHOSPHAMIDE 250 mg/msq, Day -6, -5,-4,-3

HBI 0201-ESO TCRT will be infused on Day 0, after lymphodepletion. Three dose levels will be evaluated: 1x10E9, 5x10E9 and 1x10E10.

HBI 0201-ESO TCRT

Continuous infusion of aldesleukin 18x10E6 IU/24h will be given 24 hours post HBI 0201-ESO TCRT infusion, for four days or until a dose limiting toxicity will occur that mimics cytokine release syndrome (CRS) including blood pressure drop, oliguria or confusion- all of them or any one alone.

Michal Lotem, Prof.

Yafit Halutsi

Michal Lotem, MD

A Phase I/II Dose Escalation, Safety and Efficacy Study of HBI 0201-ESO TCRT (anti-NY-ESO-1 TCR-Gene Engineered Lymphocytes) Given by Infusion to Patients with NY-ESO-1 -Expressing Metastatic Cancers

Anti-NY-ESO-1 TCR-Gene Engineered Lymphocytes Given by Infusion to Patients With NY-ESO-1 -Expressing Metastatic Cancers

A Phase I/II Dose Escalation, Safety and Efficacy Study of Anti-NY-ESO-1 T Cell Receptor (TCR)-Gene Engineered Lymphocytes Given by Infusion to Patients With NY-ESO-1 -Expressing Metastatic Cancers

Adverse events that occur following engineered T cell transfer

Hadassah Medical Organization

Other Dietary Supplements

Dehydroepiandrosterone

Adjuvants, Immunologic

DHEA (Dehydroepiandrosterone)

-DHEA is an oral supplement which will be administered on an outpatient basis at the prescribed dose daily on a 28-day cycle.

DHEA

* Baseline, Cycle 1 Day 15, and Day 1 of each cycle beginning with Cycle 2
* 7 questions with answers ranging from 0=Not At All to 4 = Very Much.

FACT-67 validated survey

Brian A Van Tine, M.D., Ph.D.

DHEA is a natural allosteric inhibitor of glucose-6-phosphate dehydrogenase (G6PD). G6PD is a key regulatory enzyme for the survival of synovial sarcoma. The investigators postulate that they can inhibit the production of NADPH in synovial sarcoma and cause cell death by using a naturally occurring G6PD inhibitor.

DHEA in Synovial Sarcoma Patients

A Phase I/II Clinical Trial of Dose-Escalating DHEA in Synovial Sarcoma Patients

* MTD is defined as the dose level immediately below the dose level at which 2 patients of a cohort (of 2 to 6 patients) experience dose-limiting toxicity during the first cycle. Dose escalations will proceed until the MTD has been reached.
* Dose-limiting toxicities are defined as one of the following events occurring during the 1st cycle of treatment thought to be possibly, probably, or definitely related to treatment:

  * Grade 3 or greater liver function test abnormalities
  * Grade 3 or greater psychiatric disorder
  * Quality of life (QOL) alteration (change in score of 30%)

* Complete response (CR): disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) must have reduction inf short axis to \<10mm, disappearance of all non-target lesions and normalization of tumor marker level.
* Partial response (PR): at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
* Stable disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diaters while on study

* PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
* Progressive disease (PD): aAppearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.

-The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
First in Man Study Investigating the Biodistribution, the Safety and Optimal Recommended Dose of a New Radiolabelled Monoclonal Antibody Targeting Frizzled Homolog 10	NCT01469975	Sarcoma, Synovi...	OTSA101-DTPA-90... OTSA101-DTPA-90... OTSA101-DTPA-90...	18 Years -	Centre Leon Berard
First in Man Study Investigating the Biodistribution, the Safety and Optimal Recommended Dose of a New Radiolabelled Monoclonal Antibody Targeting Frizzled Homolog 10	NCT01469975	Sarcoma, Synovi...	OTSA101-DTPA-90... OTSA101-DTPA-90... OTSA101-DTPA-90...	18 Years -	Centre Leon Berard
First in Man Study Investigating the Biodistribution, the Safety and Optimal Recommended Dose of a New Radiolabelled Monoclonal Antibody Targeting Frizzled Homolog 10	NCT01469975	Sarcoma, Synovi...	OTSA101-DTPA-90... OTSA101-DTPA-90... OTSA101-DTPA-90...	18 Years -	Centre Leon Berard
Anti-NY-ESO-1 TCR-Gene Engineered Lymphocytes Given by Infusion to Patients With NY-ESO-1 -Expressing Metastatic Cancers	NCT05296564	Sarcoma, Synovi... Sarcoma,Soft Ti... Melanoma Stage ... Triple Negative... Metastatic Canc... Non Small Cell ... Bladder Urothel... Neuroblastoma, ... Ovary Cancer	CYCLOPHOSPHAMID... Cyclophosphamid... HBI 0201-ESO TC... Aldesleukin	18 Years - 70 Years	Hadassah Medical Organization
DHEA in Synovial Sarcoma Patients	NCT02683148	Synovial Sarcom... Sarcoma, Synovi...	DHEA FACT-67 validat...	16 Years -	Washington University School of Medicine

Spots Global Cancer Trial Database for sarcoma, synovial