Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Rare Diseases

Sarcoma

Chondrosarcoma

Sarcoma, Clear Cell

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Neoplasms, Connective Tissue

Soft Tissue Sarcoma

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Atezolizumab

Immunoglobulins

Antibodies, Monoclonal

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

Immunologic Factors

Patients receive atezolizumab IV over 30-60 minutes on ay 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT scans and undergo biopsy and collection of blood samples on study.

Biopsy

Biospecimen Collection

Computed Tomography

A P Chen

This phase II trial studies how well atezolizumab works in treating patients with chondrosarcoma or clear cell sarcoma that is newly diagnosed, cannot be removed by surgery (unresectable), or has spread to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

PRIMARY OBJECTIVE:

I. Determine the objective response rates (ORR) using Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 of atezolizumab in adult (\>= 18 years) patients with clear cell sarcoma (CCS) and chondrosarcoma (CS).

SECONDARY OBJECTIVES:

I. Determine duration of response (DOR) using RECIST v 1.1 and/or change in clinical symptoms (time frame: baseline until disease progression, death, loss to follow-up, initiation of another anti-cancer treatment, withdrawal of consent, or study termination).

II. Measure progression-free survival (PFS) time (time frame: baseline until disease progression, death, loss to follow-up, initiation of another anti-cancer treatment, withdrawal of consent, or study termination).

III. Assess the number of activated CD8+ T cells infiltrating the tumor before and after atezolizumab treatment, and correlate treatment-induced changes with clinical response.

EXPLORATORY OBJECTIVES:

I. Compare RECIST v 1.1 versus (vs) immune RECIST (iRECIST) in patients with CCS and CS on atezolizumab.

II. Examine changes in PD-1/PD-L1 expression in the tumor microenvironment before and after atezolizumab treatment, and correlate treatment-induced changes with clinical response.

III. Evaluate potential associations between atezolizumab activity and tumor genomic alterations.

OUTLINE:

Patients receive atezolizumab intravenously (IV) over 30-60 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) scans and undergo biopsy and collection of blood samples on study.

After completion of study treatment, patients are followed up to 90 days.

Testing Atezolizumab in People 2-17 Years Old With Clear Cell Sarcoma or Advanced Chondrosarcoma

A Phase 2 Study of Anti-PD-L1 Antibody (Atezolizumab) in Chondrosarcoma and Clear Cell Sarcoma

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

Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

ORR was measured using the Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1, which involves the following response definitions. Complete Response (CR): disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. 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 (PD), taking as reference the smallest sum diameters while on study. Progressive Disease (PD): at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. The appearance of one or more new lesions is also considered progressions.

Duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Complete Response (CR): disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Progression was measured using the Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 and/or change in clinical symptoms. Progressive Disease (PD): is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. The appearance of one or more new lesions is also considered progressions.

PFS is the time interval from start of treatment to documented evidence of disease progression, measured by the Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1, or death from any cause, whichever comes first. Progressive Disease (PD): at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. The appearance of one or more new lesions is also considered progressions.

Activated CD8+ T cells will be detected by multiplex immunofluorescence assays and will be defined by the expression of T cell receptor (TCR) activation (Zeta chain phosphorylation) or phosphorylated Zap70 (pY493); CD8+ cells present within the tumor section that are positive for these markers will be quantified.

National Cancer Institute (NCI)

The descriptions and grading scales found in the revised National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 were utilized for adverse event (AE) reporting. An adverse event that began in one cycle and resolved in another cycle is considered a single adverse event.

Participants with clear cell sarcoma receive atezolizumab intravenous (IV) over 30-60 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Participants undergo computed tomography (CT) scans and undergo biopsy and collection of blood samples on study.

Arm 1 Atezolizumab 1200 mg Intravenous (IV) on Day 1, Subgroup 1: Clear Cell Sarcoma (CCS)

Participants with conventional chondrosarcoma, grade 2 or 3, receive atezolizumab intravenous (IV) over 30-60 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Participants undergo computed tomography (CT) scans and undergo biopsy and collection of blood samples on study.

Arm 1 Atezolizumab 1200 mg IV on Day 1, Subgroup 2: Conventional Chondrosarcoma (CS)(Grade 2 or 3)

Participants with dedifferentiated chondrosarcoma receive atezolizumab intravenous (IV) over 30-60 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Participants undergo computed tomography (CT) scans and undergo biopsy and collection of blood samples on study.

Arm 1 Atezolizumab 1200 mg Intravenous on Day 1, Subgroup 3: Dedifferentiated Chondrosarcoma (CS)

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Canada

United States

Region of Enrollment

Alice P. Chen

Complete Response

Partial Response

Stable Disease

Progressive Disease

Unknown (not assessed)

Objective Response Rates (ORR)

The analysis population was to include all participants with an objective response (complete or partial). Because no objective responses were observed, there was no evaluable population and data were not collected.

Duration of Response (DOR) or Change in Clinical Symptoms

Progression-free Survival (PFS) Time

Number of Activated Cluster of Differentiation 8 (CD8+) T Cells Infiltrating the Tumor

Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)

Overall Study

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Musculoskeletal Diseases

Carcinoma

Carcinoma, Squamous Cell

Breast Neoplasms

Triple Negative Breast Neoplasms

Recurrence

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Thyroid Neoplasms

Thyroid Diseases

Histiocytoma, Malignant Fibrous

Osteosarcoma

Carcinosarcoma

Mixed Tumor, Mullerian

Bone Neoplasms

Thyroid Carcinoma, Anaplastic

Giant Cell Tumors

Giant Cell Tumor of Bone

Histiocytoma

Neoplasms, Glandular and Epithelial

Breast Diseases

Skin Diseases

Disease Attributes

Endocrine System Diseases

Neoplasms, Bone Tissue

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

Gonadal Disorders

Head and Neck Neoplasms

Bone Diseases

Neoplasms, Fibrous Tissue

Ovarian Cancer

Ovarian Epithelial Cancer

Undifferentiated Pleomorphic Sarcoma

Malignant Mixed Mullerian Tumor

Ovarian Carcinosarcoma

Anaplastic Thyroid Cancer

Antirheumatic Agents

Anti-Infective Agents

Analgesics

Amino Acids

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Aldesleukin

Nivolumab

Ipilimumab

Interleukin-2

Immunosuppressive Agents

Antineoplastic Agents, Alkylating

Alkylating Agents

Analgesics, Non-Narcotic

Anti-HIV Agents

Anti-Retroviral Agents

Antiviral Agents

Serine

Ipilimumab will be administered as a single dose prior to tumor resection. Nivolumab will be administered once prior to tumor resection. Patients receive cyclophosphamide IV over 2 hours on days -7 and -6, fludarabine IV over 15-30 minutes daily on days -5 to -1, LN-145-S1 IV over 45 minutes on day 0 and aldesleukin IV over 30 minutes on days 1-4 for up to 6 doses. Within 12 weeks after receiving LN-145-S1, patients receive nivolumab IV over 30 minutes every 4 weeks in the absence of disease progression or unacceptable toxicity. The second dose will be administered prior to TIL administration and dosing will continue every 4 weeks and continued until unacceptable toxicity, progression, or start of another cancer therapy.

Patients receive cyclophosphamide IV over 2 hours on days -7 and -6, fludarabine IV over 15-30 minutes daily on days -5 to -1, autologous tumor infiltrating lymphocytes LN-145 IV over 45 minutes on day 0 and aldesleukin IV over 30 minutes on days 1-4 for up to 6 doses.

Autologous Tumor Infiltrating Lymphocytes LN-145

Autologous Tumor Infiltrating Lymphocytes LN-145-S1

Quality-of-Life Assessment

Questionnaire Administration

Amir A Jazaeri

This phase II trial studies how well autologous tumor infiltrating lymphocytes LN-145 (LN-145) or LN-145-S1 works in treating patients with ovarian cancer, triple negative breast cancer (TNBC), anaplastic thyroid cancer, osteosarcoma, or other bone and soft tissue sarcomas that do not respond to treatment (refractory) or that has come back (relapsed).

LN-145 is made by collecting and growing specialized white blood cells (called T-cells) that are collected from the patient's tumor. LN-145-S1 is made using a modified process that chooses a specific portion of the T-cells. The T cells may specifically recognize, target, and kill the tumor cells.

PRIMARY OBJECTIVE:

I. To evaluate efficacy using objective response rate (ORR) using Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 in each cohort.

SECONDARY OBJECTIVES:

I. Determine the disease control rate (DCR) within and across cohorts. II. Determine the duration of response (DOR). III. Determine progression-free survival (PFS) and overall survival (OS). IV. Further characterize the safety profile of adoptive cell therapy with tumor infiltrating lymphocytes (TIL) across multiple tumor types.

EXPLORATORY OBJECTIVES:

I. Establish duration of tumor-infiltrating lymphocyte (TIL) persistence. II. Compare the molecular and immunological features of tumors before and after TIL therapy.

III. Prospectively evaluate the existing immunotherapy response criteria (immune-related \[ir\]RECIST) as the best response assessment tool for TIL therapy among a diverse group of solid tumors.

IV. To investigate TIL attributes (CD8 percentage \[%\], CD27 and CD28 expression) and correlation with response to therapy.

V. Assess tumor marker (CA-125) response in patients who produce this tumor marker.

VI. To assess Health-Related Quality of Life (HRQOL).

OUTLINE: Patients are assigned to 1 of 2 cohorts.

THYROID CANCER COHORT: Patients receive cyclophosphamide intravenously (IV) over 2 hours on days -7 and -6, fludarabine IV over 15-30 minutes daily on days -5 to -1, autologous tumor infiltrating lymphocytes LN-145 IV over 45 minutes on day 0 and aldesleukin IV over 30 minutes on days 1-4 for up to 6 doses.

ICI OVARIAN CANCER, OSTEOSARCOMA, Triple Negative Breast Cancer, or OTHER BONE AND SOFT TISSUE SARCOMAS COHORT: Within 2-4 weeks prior to surgery, patients receive a single dose of nivolumab IV over 30 minutes, followed by a single dose of ipilimumab IV over 30 minutes Patients receive cyclophosphamide IV over 2 hours on days -7 and -6, fludarabine IV over 15-30 minutes daily on days -5 to -1, LN-145-S1 IV over 45 minutes on day 0 and aldesleukin IV over 30 minutes on days 1-4 for up to 6 doses. Within 12 weeks after receiving LN-145-S1, patients receive nivolumab IV over 30 minutes every 4 weeks in the absence of disease progression or unacceptable toxicity.

For cohorts treated without immune checkpoint inhibitors, completion of treatment is defined as having received any volume of LN-145/LN-145-S1 infusion followed by at least 1 dose of adjuvant IL-2. For cohorts treated with TIL + ICI, completion of treatment will correspond to the last dose of nivolumab or IL2 (if the subject is deemed unsuitable to receive adjuvant nivolumab). Patients are followed up at 18 weeks, 6, 9, 12, 18 and 24 months, then every 3 months for at least 3 years.

LN-145 or LN-145-S1 in Treating Patients With Relapsed or Refractory Ovarian Cancer, Triple Negative Breast Cancer (TNBC), Anaplastic Thyroid Cancer, Osteosarcoma, or Other Bone and Soft Tissue Sarcomas

Clinical Study to Assess Efficacy and Safety of LN-145/LN-145-S1 (Autologous Centrally Manufactured Tumor Infiltrating Lymphocytes) Across Multiple Tumor Types

Determined by T-cell receptor (TCR) sequencing of infused T cells serially isolated following LN-145/LN-145-S1 infusion, or alternatively iRepertoire assessment of messenger ribonucleic acid for the TCRs.

Pearson correlation coefficient and linear regression, when appropriate, will be used to quantify the relationship between phenotypic attributes (CD8 percentage \[%\], CD27 and CD28 expression, etc.) and response to therapy.

Pearson correlation coefficient and linear regression, when appropriate, will be used to quantify the relationship between phenotypic attributes (CD8 %, CD27 and CD28 expression, etc.) and response to therapy.

Paired t-test will be used to examine the molecular and immunological features of tumors before and after TIL therapy.

Assessed per the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) questionnaire.

Assessed by Response Evaluation Criteria in Solid Tumors version 1.1. Estimation will use 80% confidence intervals by the Wilson score method.

Will be summarized using Kaplan-Meier estimates.

Iovance Biotherapeutics, Inc.

M.D. Anderson Cancer Center

Liposarcoma

Liposarcoma, Myxoid

Chondrosarcoma, Mesenchymal

Neoplasms, Adipose Tissue

Myxoid Liposarcoma

Sirolimus

Anti-Bacterial Agents

Antibiotics, Antitubercular

Clotrimazole

Miconazole

Antifungal Agents

combining sirolimus 4mg daily orally and cyclophosphamide 200mg day 1 to 7 and 15 to 21 orally in a 4 week schedule

sirolimus and cyclophosphamide

Hans Gelderblom, Prof

Chondrosarcoma and liposarcoma consists of different subtypes with a wide range of patient survival. Current treatment options consist of wide surgical resection, however for patients with a local recurrence or metastatic disease the outcome is poor. New treatment options being evaluated and mouse models show in vivo that mammilian target of rapamycin (mTOR) inhibition can prevent tumour growth. mTOR is an kinase that is present in two complexes and thereby activates multiple pathways. Aberrant mTOR signalling is known to be involved in cancer cell survival. Several clinical studies for patients with bone or soft tissue sarcoma treated with mTOR inhibitors have been conducted and they show promising results. From these studies the investigators can conclude that the combination of an mTOR inhibitor with cyclophosphamide shows promising results in chondrosarcoma. With the lack of other treatment options for unresectable and metastatic chondrosarcoma or myxoid liposarcoma the Eurosarc consortium (www.eurosarc.eu) decided to treat these patients in a standardised way according to a common protocol with the combination of sirolimus and cyclophosphamide using the growth modulation index for evaluation in the current clinical study protocol.

Sirolimus and Cyclophosphamide in Metastatic or Unresectable Myxoid Liposarcoma and Chondrosarcoma

A Phase 2, Single Arm, Multi Center Trial Evaluating the Efficacy of the COmbination of Sirolimus and cYclophosphamide in Metastatic or Unresectable Myxoid Liposarcoma and chOndrosarcoma

GMI: Time to progression during sirolimus/cyclophosphamide treatment (TTP2) divided by time to progression before start of this treatment TTP1

Leiden University Medical Center

Prof A.J. Gelderblom

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Testing Atezolizumab in People 2-17 Years Old With Clear Cell Sarcoma or Advanced Chondrosarcoma	NCT04458922	Central Chondro... Central Chondro... Dedifferentiate... Metastatic Clea... Metastatic Prim... Unresectable Pr...	Atezolizumab Biopsy Biospecimen Col... Computed Tomogr...	2 Years -	National Cancer Institute (NCI)
LN-145 or LN-145-S1 in Treating Patients With Relapsed or Refractory Ovarian Cancer, Triple Negative Breast Cancer (TNBC), Anaplastic Thyroid Cancer, Osteosarcoma, or Other Bone and Soft Tissue Sarcomas	NCT03449108	Bone Sarcoma Dedifferentiate... Giant Cell Tumo... Malignancy in G... Malignant Solid... Ovarian Carcino... Platinum-Resist... Poorly Differen... Recurrent Osteo... Recurrent Ovari... Refractory Oste... Soft Tissue Sar... Thyroid Gland A... Thyroid Gland S... Undifferentiate... Triple Negative...	Aldesleukin Autologous Tumo... Autologous Tumo... Cyclophosphamid... Fludarabine Ipilimumab Nivolumab Quality-of-Life... Questionnaire A...	16 Years - 70 Years	M.D. Anderson Cancer Center
Sirolimus and Cyclophosphamide in Metastatic or Unresectable Myxoid Liposarcoma and Chondrosarcoma	NCT02821507	Conventional Ch... Myxoid Liposarc... Mesenchymal Cho... Dedifferentiate...	sirolimus and c...	18 Years -	Leiden University Medical Center
Testing Atezolizumab in People 2-17 Years Old With Clear Cell Sarcoma or Advanced Chondrosarcoma	NCT04458922	Central Chondro... Central Chondro... Dedifferentiate... Metastatic Clea... Metastatic Prim... Unresectable Pr...	Atezolizumab Biopsy Biospecimen Col... Computed Tomogr...	2 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for dedifferentiated chondrosarcoma