Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Nervous System Diseases

Rare Diseases

Sarcoma

Liposarcoma

Histiocytoma, Malignant Fibrous

Testicular Neoplasms

Chondrosarcoma

Fibrosarcoma

Histiocytoma

Leiomyosarcoma

Rhabdomyosarcoma

Sarcoma, Synovial

Neurofibrosarcoma

Sarcoma, Alveolar Soft Part

Neoplasms, Connective and Soft Tissue

Myosarcoma

Neoplasms by Histologic Type

Soft Tissue Sarcoma

Synovial Sarcoma

Malignant Peripheral Nerve Sheath Tumor

All Drugs and Chemicals

Vaccines

Immunomodulating Agents

Immunologic Factors

Autologous dendritic cell vaccine loaded with allogeneic tumor lysate expression of cancer testis antigens

Autologous dendritic cell vaccine

Yuriy Komarov, PhD

The purpose of this study is to achieving a six-month progression free survival (PFS) of patients receiving autologous dendritic cell vaccine (ADKV) loaded with allogeneic tumor lysate expression of cancer-testis antigens (CTA) in patients with soft tissue sarcomas

Vaccination is carried out on the planned days ± 3 days

1. All examinations must be performed before the vaccine is administered.

   * Full physical examination.
   * Assessment of vital signs (blood pressure, temperature, heart rate), the general condition of the patient and physical activity.
   * Evaluation of concomitant therapy.
   * Assessment of vital signs.
   * Laboratory safety and immunological indicators
   * Assessment of adverse events, symptoms and syndromes of the disease.
2. Introduction of CV in accordance with the dose determined for a given vaccination (see section 9.2. - procedures for delivery and use)
3. After administration, patients are observed for at least 1 hour. An assessment of vital indicators. Undesirable effects detected at the introduction are recorded.

Autologous Dendritic Cell Vaccine in Patients With Soft Tissue Sarcoma

Non-randomized Single-center Study Phase II Evaluating the Efficacy and Toxicity of Autologous Dendritic Cell Vaccine Loaded With Allogeneic Tumor Lysate Expression of Cancer Testis Antigens in Patients With Soft Tissue Sarcoma

Achieving a six-month time to progression (PFS) 40% of patients receiving ADKV loaded with allogeneic tumor lysate expressing PTA in patients with soft tissue sarcomas

The length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse. In a clinical trial, measuring the progression-free survival is one way to see how well a new treatment works

The length of time from either the date of diagnosis or the start of treatment for a disease, such as cancer, that half of the patients in a group of patients diagnosed with the disease are still alive. In a clinical trial, measuring the median overall survival is one way to see how well a new treatment works

The percentage of patients whose cancer shrinks or disappears after treatment.

Сhanging level of T lymphocytes subpopulation in peripheral blood

N.N. Petrov National Medical Research Center of Oncology

Alveolar Soft Part Sarcoma

Antineoplastic Agents

Amino Acids

Endothelial Growth Factors

Mitogens

Tyrosine Kinase Inhibitors

Cediranib

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Adult participants will be treated with 30 mg by mouth once a day for 28 days (28-day cycles).

Pediatric participants (\<16 years old) will be treated with 12 mg/m\^2/day once a day for 28 days (28-day cycles).

Cediranib (AZD2171), a vascular endothelial growth factor (VEGF)/KIT tyrosine kinase inhibitor, has demonstrated antitumor activity in early phase clinical trials in adult and pediatric patients with Alveolar Soft Part Sarcoma (ASPS).

AZD2171

Alice P Chen, M.D.

Background:

* Alveolar soft part sarcoma is a type of cancer that develops in tissues that connect, support, or surround other organs in the body. It relies heavily on new blood vessels to grow and spread through the body. There is no effective systemic treatment for patients with alveolar soft part sarcoma.
* The drug AZD2171 (cediranib) is an experimental drug, not yet approved by the Food and Drug Administration. The drug blocks the creation of new blood vessels. The drug has had initial clinical trials, and researchers are interested in determining whether cediranib is effective in inhibiting tumor growth in individuals who have alveolar soft part sarcoma.

Objectives:

- To find out whether AZD2171 works in patients who have alveolar soft part sarcoma.

Eligibility:

- Individuals 18 years of age and older who have been diagnosed with alveolar soft part sarcoma.

Design:

* After an initial screening visit, patients will take AZD2171 by mouth once a day, every day for the duration of the study. The treatment will be given in 28-day cycles.
* Patients will keep a study diary to record the doses taken, any missed doses, and any side effects.
* Patients will have the following tests and procedures during the treatment period: clinic visit with physical examination every 2 weeks during cycles 1 and 2, then at the start of each subsequent cycle, regular blood pressure monitoring, blood and urine tests, heart function tests, imagining scans to evaluate tumor size and response to the treatment, and possible tumor biopsy.

Background:

Alveolar soft part sarcoma (ASPS) is a rare, highly vascular tumor accounting for less than 1% of soft tissue sarcomas. There is no effective systemic treatment for patients with metastatic ASPS. Little is known with regards to relevant molecular markers as potential therapeutic targets. Cediranib (AZD2171), a vascular endothelial growth factor (VEGF)/KIT tyrosine kinase inhibitor, has recently demonstrated antitumor activity in early phase clinical trials, which included 7 adult and 3 pediatric patients with ASPS.

Objectives:

Adult patients:

* To determine the response rate (Partial Response (PR) + Complete Response (CR)) of AZD2171 in adult patients with ASPS.
* To compare gene expression profiles between pre-treatment and post-treatment biopsy specimens.

Pediatric patients:

-To determine if pediatric patients with ASPS will experience at least a minimal response rate when treated with AZD2171

Eligibility:

Patients must have histologically or cytologically confirmed metastatic alveolar soft part sarcoma.

* Less than 16 years old. Body surface area (BSA) must be greater than or equal to 1.04 m\^2 and subject must be able to swallow tablets.
* Adequate organ function.

Design:

Adult patients will be treated with AZD2171 at 30 mg by mouth once a day for 28 days (28-day cycles). Pediatric patients (\< 16 years old) will be treated with 12 mg/m\^2/day once a day for 28 day (28-day cycles).

Blood pressure will be monitored weekly for the first 2 cycles then every 2 weeks for the remainder of the study (unless patients have experienced elevated blood pressure requiring drug therapy).

Computed tomography (CT) scans will be performed at baseline and every 2 cycles for restaging during the first 18 months; after 18 and 36 months, restaging CT scans will be performed every 3 or 4 cycles, respectively.

The study will be conducted using an optimal two-stage design in both pediatric and adult patients. The portion in adults will rule out an unacceptably low 5% clinical response rate (PR+CR) in favor of a modestly high response rate of 25%. In pediatric patients, the study will rule out an unacceptably low 5% overall clinical response rate (CR + PR) in favor of a higher response rate of 35%.

Optional biopsies will be performed in adult patients only at baseline and after 3-5 days of treatment (Day 3 (D3)-Day 5 (D5)) to evaluate early drug effect. A third optional biopsy after completion of 4 weeks of therapy (between Cycle 1 Day 28 (C1D28) and Cycle 2 Day 7 (C2D7)) may be collected with the intention of providing further information about disease response to treatment. Depending on results of initial gene expression profiles, the timing of the biopsies may be adjusted, but without change in total number of biopsies per patient.

In a retrospective pilot study, CT scans from 20 consecutive off-study patients will be re-reviewed. Response Evaluation Criteria in Solid Tumors (RECIST) imaging measurements will be compared to volumetric density (Total Volume of Viable Tumor, TVVT) CT measurements. The objective is to establish whether volumetric density/percent necrosis algorithms such as TVVT more accurately assess extent of disease and response to therapy than standard RECIST criteria.

The total accrual ceiling is 73 participants (60 adult and 13 pediatric patients).

Phase II Study of Cediranib (AZD2171) in Patients With Alveolar Soft Part Sarcoma

All individual participant data (IPD) will be shared with intramural investigators upon request.

Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST)v1.0. A minimal response is defined as a 5% overall response rate (Partial Response (PR) + Complete Response (CR)

Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response is disappearance of all no-target lesions and normalization of tumor marker level. Partial response is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.

Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.0. Complete Response is disappearance of all target lesions and normalization of tumor marker level. Partial response is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions. Progressive disease is at least a 20% increase in the sum of the LD of target lesions. Stable disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease.

Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in 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.

National Cancer Institute (NCI)

Principal Investigator

Adult participants will be treated with 30 mg by mouth once a day for 28 days (28-day cycles).

AZD2171: Cediranib (AZD2171), a vascular endothelial growth factor (VEGF)/KIT tyrosine kinase inhibitor, has demonstrated antitumor activity in early phase clinical trials in adult and pediatric patients with Alveolar Soft Part Sarcoma (ASPS).

Adult Participants w/Alveolar Soft Part Sarcoma

Pediatric participants (\<16 years old) will be treated with 12 mg/m\^2/day once a day for 28 days (28-day cycles).

AZD2171: Cediranib (AZD2171), a vascular endothelial growth factor (VEGF)/KIT tyrosine kinase inhibitor, has demonstrated antitumor activity in early phase clinical trials in adult and pediatric patients with Alveolar Soft Part Sarcoma (ASPS).

Pediatric Participants w/Alveolar Soft Part Sarcoma

Pediatric participants will be treated with 12 mg/m\^2/day once a day for 28 days (28-day cycles).

AZD2171: Cediranib (AZD2171), a vascular endothelial growth factor (VEGF)/KIT tyrosine kinase inhibitor, has demonstrated antitumor activity in early phase clinical trials in adult and pediatric patients with Alveolar Soft Part Sarcoma (ASPS).

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

ECOG status for adults indicates level of participant activity. 0 = fully active

1. = ambulatory and can perform light work
2. = capable of all self-care but unable to perform work activities

ECOG applies to the adult participants only.

Eastern Cooperative Oncology Group (ECOG) Status

100%

Lansky/Karnofsky for pediatric participants indicates level of activity. 100% = normal activity with no signs/symptoms of disease 90% = normal activity with a few signs/symptoms of disease 80% =normal activity with some difficulty

Lansky/Karnofsky applies to the pediatric participants only.

Lansky/Karnofsky Performance Status

Prior Resection

Prior Radiation

Applies to the pediatric participants only.

Prior Systemic Therapy

≥3

Prior Systemic Therapies

Dr. Alice Chen

Minimal Response Rate in Pediatric Participants With Alveolar Soft Part Sarcoma (ASPS)

Complete Response

Partial Response

45/46 participants were analyzed because one participant was not treated.

Number of Participants With a Response (Partial Response (PR) + Complete Response (CR)) of AZD2171 in Adult Participants With Alveolar Soft Part Sarcoma (ASPS)

Stable Disease

Progressive Disease

Number of Participants With a Best Observed Response

45/46 participants were analyzed because one participant did not receive any treatment on the trial.

Number of Participants With a Best Response

Number of Participants With Serious and Non-serious Adverse Events

Overall Study

Symptoms and General Pathology

Disease Progression

Oculocerebral Syndrome With Hypopigmentation

Sunitinib

Angiogenesis Inhibitors

Growth Inhibitors

Patients will be randomized to receive cediranib (30 mg) or sunitinib malate (37.5 mg) orally, once a day in 28-day cycles

At the time of disease progression, patients will cross over to the other treatment arm after a 2-week wash-out period

Cediranib, a small molecule inhibitor of VEGF receptor tyrosine kinases, is showing preliminary evidence of activity in patients with ASPS.

Sunitinib, a small molecule inhibitor of VEGF receptor tyrosine kinases, is showing preliminary evidence of activity in patients with ASPS.

Background:

* Alveolar soft part sarcoma (ASPS) is a rare, highly vascular tumor accounting for less than 1% of soft tissue sarcomas. There is no effective systemic treatment for patients with metastatic ASPS. Little is known with regards to relevant molecular markers as potential therapeutic targets.
* Cediranib (AZD2171) and sunitinib (SU011248), oral small molecule inhibitors of VEGF receptor tyrosine kinases, are showing preliminary evidence of activity in patients with ASPS.

Objectives:

* Part I: Determine the objective response rate (ORR) of single-agent cediranib and single-agent sunitinib malate in patients with advanced ASPS.
* Part II: Determine the ORR of cediranib in patients who progress on the sunitinib arm, and determine the ORR of sunitinib in patients who progress on the cediranib arm.
* Determine the progression-free survival (PFS) at 24 weeks for single-agent cediranib and

single-agent sunitinib malate in patients with advanced ASPS.

Eligibility:

* Patients aged greater than or equal to 16 years with histologically or cytologically confirmed metastatic ASPS.
* Patients must show evidence of objective disease progression per RECIST 1 on scans within the 3-month period immediately preceding enrollment. Both scans used to determine disease progression should have been obtained within this 6-month period.
* Patients with newly diagnosed, unresectable, measurable, metastatic ASPS who show clinical evidence of disease progression will be eligible.
* Patients must not have received treatment with any VEGF receptor tyrosine kinase inhibitor (e.g., cediranib, sunitinib, pazopanib, sorafenib); however, prior treatment with bevacizumab is allowed.

Design:

* Part I: Patients will be randomized to receive cediranib (30 mg) or sunitinib malate (37.5 mg) orally, once a day in 28-day cycles.
* Part II: At the time of disease progression, patients will cross over to the other treatment arm after a 2-week wash-out period.
* Appropriate anatomic imaging studies will be performed at baseline and every 2 cycles for restaging.
* The study will be conducted using an optimal two-stage design to rule out an unacceptably low 15% clinical response rate (PR+CR) in favor of a modestly high response rate of 40%.

The study will initially enroll 10 evaluable patients in each arm. If 0 or 1 of the 10 patients has a clinical response, then no further patients will be accrued. If 2 or more the first 10 patients have a response, then accrual continues to a total of 22 patients in each arm.

Background:

* Alveolar soft part sarcoma (ASPS) is a rare, highly vascular tumor accounting for less than 1% of soft tissue sarcomas. There is no effective systemic treatment for patients with metastatic ASPS. Little is known with regards to relevant molecular markers as potential therapeutic targets.
* Cediranib (AZD2171) and sunitinib (SU011248), oral small molecule inhibitors of VEGF receptor tyrosine kinases, are showing preliminary evidence of activity in patients with ASPS.

Objectives:

* Part I: Determine the objective response rate (ORR) of single-agent cediranib and single-agent sunitinib malate in patients with advanced ASPS.
* Part II: Determine the ORR of cediranib in patients who progress on the sunitinib arm, and determine the ORR of sunitinib in patients who progress on the cediranib arm.
* Determine the progression-free survival (PFS) at 24 weeks for single-agent cediranib and

single-agent sunitinib malate in patients with advanced ASPS.

Eligibility:

Status Update: Patients enrolled after Amendment G (version dated 08/16/2013), will be

evaluated and compared to the first 13 patients by the study statistician and the Principal

Investigator. Patients with newly diagnosed ASPS with clinical evidence of disease progression will also be assessed separately.

* Patients aged greater than or equal to 16 years with histologically or cytologically confirmed metastatic ASPS.
* Patients must show evidence of objective disease progression per RECIST 1 on scans within the 3-month period immediately preceding enrollment. Both scans used to determine disease progression should have been obtained within this 6-month period.
* Patients with newly diagnosed, unresectable, measurable, metastatic ASPS who show clinical evidence of disease progression will be eligible.
* Patients must not have received treatment with any VEGF receptor tyrosine kinase inhibitor (e.g., cediranib, sunitinib, pazopanib, sorafenib); however, prior treatment with bevacizumab is allowed.

Design:

* Two sets of patients will be enrolled and assessed in separate cohorts: a) patients with non-newly diagnosed ASPS and b) patients with newly diagnosed ASPS
* Part I: Patients will be randomized to receive cediranib (30 mg) or sunitinib malate (37.5 mg) orally, once a day in 28-day cycles. As of May 6, 2019, we have closed the cediranib arm of the newly diagnosed ASPS cohort due to inadequate activity per the statistical plan; all newly diagnosed ASPS patients will be assigned to the sunitinib malate treatment arm.
* Part II: At the time of disease progression, patients will cross over to the other treatment arm after a 2-week wash-out period. As of May 6, 2019, patients in the newly diagnosed ASPS cohort are not eligible to cross over to the cediranib treatment arm, which was closed due to inadequate activity.
* Appropriate anatomic imaging studies will be performed at baseline and every 2 cycles for restaging.
* The study will be conducted using an optimal two-stage design to rule out an unacceptably low 15% clinical response rate (PR+CR) in favor of a modestly high response rate of 40%.

The study will initially enroll 10 evaluable patients in each arm. If 0 or 1 of the 10 patients has a clinical response, then no further patients will be accrued. If 2 or more the first 10 patients have a response, then accrual continues to a total of 22 patients in each arm.

Sunitinib or Cediranib for Alveolar Soft Part Sarcoma

A Phase II Trial In Which Patients With Metastatic Alveolar Soft Part Sarcoma Are Randomized to Either Sunitinib or Cediranib Monotherapy, With Cross-Over at Disease Progression

.All IPD recorded in the medical record will be shared with intramural investigators upon request.

Objective responses will be determined by RECIST criteria

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Autologous Dendritic Cell Vaccine in Patients With Soft Tissue Sarcoma	NCT01883518	Sarcoma Neoplasms, Conn...	Autologous dend...	18 Years -	N.N. Petrov National Medical Research Center of Oncology
Phase II Study of Cediranib (AZD2171) in Patients With Alveolar Soft Part Sarcoma	NCT00942877	Sarcoma, Alveol...	AZD2171	- 16 Years	National Institutes of Health Clinical Center (CC)
Sunitinib or Cediranib for Alveolar Soft Part Sarcoma	NCT01391962	Sarcoma, Alveol...	Cediranib Sunitinib	16 Years - 120 Years	National Institutes of Health Clinical Center (CC)
Sunitinib or Cediranib for Alveolar Soft Part Sarcoma	NCT01391962	Sarcoma, Alveol...	Cediranib Sunitinib	16 Years - 120 Years	National Institutes of Health Clinical Center (CC)

Spots Global Cancer Trial Database for sarcoma, alveolar soft part