Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Rare Diseases

Sarcoma

Ovarian Neoplasms

Carcinosarcoma

Mixed Tumor, Mullerian

Leiomyosarcoma

Adenoma, Pleomorphic

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Ovarian Cancer

Soft Tissue Sarcoma

Malignant Mixed Mullerian Tumor

Uterine Carcinosarcoma

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Carboplatin

Doxorubicin

Liposomal doxorubicin

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Subjects will receive PegLiposomal Doxorubicin (40mg/m²) and Carboplatin (AUC6) every 28 days. Treatment period up to 6 months (therapy can be continued in case of tumor response and benefit for the patient)

PegLiposomal Doxorubicin, intravenous, 40mg/m², every 28 days for up to 6 months

PegLiposomal Doxorubicin

Carboplatin, intravenous, AUC 6, every 28 days for up to 6 months

Philipp Harter, MD

Uterine sarcomas account for less than 5% of all carcinomas of the uterine corpus. The prognosis of these patients is extremely limited. Recurrence rates of 50-60% are reported even for early-stage disease (FIGO I/II). Median overall survival is below 12 months in patients with advanced or metastatic disease.

Ovarian carcinosarcoma is extremely rare among ovarian malignancies (\< 2%). That is why there is insufficient data as a basis for establishing a gold standard. As a result, these cases tend to be treated in the same way as uterine sarcomas or epithelial ovarian malignancies in clinical practice.

On the basis of data published to date on the treatment of mixed mesenchymal-epithelial tumors, it is clear that the treatments commonly used to date have limited activity while producing clinically relevant toxicity. The regimes verified so far (Cisplatin / Ifosfamide, Ifosfamide/Paclitaxel and Gemcitabine/Docetaxel) exhibit a considerable side effect spectrum and are only rarely feasible on clinical everyday life conditions, so e. g. the rate of withdrawals due to toxicity was in a study collective of selected females treated with the last combination at 40 %. The physician has to check in every individual case if one of the above mentioned combinations is feasible. The search for alternative effective and better tolerated treatment options is essential. The toxicity data on the carboplatin-PLD combination are known, and efficacy has been identified in small cohorts.

The objective of this study is to explore the efficacy of combination PLD-carboplatin treatment in a larger patient population.

This study in patients with mesenchymal or mixed epithelial mesenchymal tumors of the ovary or uterus is designed as a prospective single-arm, open - label, multicenter phase II study to evaluate the efficacy of PegLiposomal Doxorubicin and Carboplatin combination chemotherapy.

40 patients will be recruited to receive PegLiposomal Doxorubicin (PLD) in a continuous i. v. infusion of at least 60 minutes at a dose of 40 mg/m2 on Day 1, followed by a 30-minute i. v. carboplatin infusion according to AUC 6 (formula devised by Calvert et al).

Patients will get outpatients treatment. At screening the patients' eligibility will be assessed, their baseline and demographic characteristics obtained, and baseline values for the effect variables collected. Patients with measurable lesions, non-measurable lesions or histological documentation will be included into this trial. Measurable lesion and non-measurable lesions will be documented by x-ray, ultrasound, computed tomography or MRI.

The patients' safety will be monitored during therapy until recovery of toxicities.

In patients with measurable lesions at baseline, the (post)-treatment values for effect according to the RECIST criteria will be collected as shown in table 6. CR, PR and SD have to be confirmed by a repeat measurement after an interval of at least four weeks.

Follow-up is scheduled every three months during the first two years after the end of treatment.

As from year 3 the follow-up takes place outside the study in the context of general aftercare.

Multicenter Trial With PegLiposomal Doxorubicin and Carboplatin Combination Chemotherapy in Gynecological Sarcomas and Mixed Epithelial-Mesenchymal Tumors

Phase II Study Evaluating PegLiposomal Doxorubicin (PLD) and Carboplatin Combination Chemotherapy in Gynecological Sarcomas and Mixed Epithelial-Mesenchymal Tumors

Merck Sharp & Dohme LLC

AGO Study Group

Digestive System Diseases

Skin and Connective Tissue Diseases

Gastrointestinal Stromal Tumors

Gastrointestinal Neoplasms

Digestive System Neoplasms

Neoplasms, Connective Tissue

Gastrointestinal Diseases

Amino Acids

Ponatinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Tyrosine

Participants with KIT exon 11-mutant GIST.

Participants with GIST that lack KIT exon 11 mutations (Cohort B).

Ponatinib 45 mg, tablets, orally, once-daily.

The purpose of this study is to evaluate the efficacy and safety of ponatinib in participants with metastatic and/or unresectable gastrointestinal stromal tumor (GIST) following failure of prior tyrosine kinase inhibitor (TKI) therapy.

This is a non-randomized, open label, multi-center phase 2 study to evaluate the efficacy and safety of ponatinib in participants with metastatic and/or unresectable GIST after failure of prior TKI therapy. Participants whose tumors have an activating mutation in exon 11 of cellular KIT (KIT) will be enrolled into Cohort A. Participants whose tumors have other activating mutations will be enrolled into in Cohort B.

The primary objective is to assess clinical benefit in participants with KIT exon 11-mutant GIST (Cohort A) defined as clinical benefit rate (CBR), which is the composite of complete response (CR), partial response (PR) and stable disease (SD) lasting greater than or equal to (\>=) 16 weeks per modified response evaluation criteria in solid tumors (RECIST 1.1) as a measure of disease control. The secondary objective is to assess clinical benefit in participants with GIST that lacks an activating KIT exon 11 mutation (Cohort B) and in the total participant population. The efficacy assessments are tumor response using RECIST Version 1.1, modified for GIST and assessment of progression-free survival (PFS) and overall survival (OS). The safety assessments include routine physical and laboratory evaluations, electrocardiograms (ECGs), echocardiograms (ECHOs), and adverse event (AE) monitoring. Other assessments include optional 18F fluorodeoxyglucose positron emission tomography (FDG-PET); optional pre- and post-treatment tumor biopsy for pharmacodynamic studies; and pharmacokinetics (PK). It is estimated that accrual will be complete within 1 year; the total estimated duration of the study is 3 years.

A Phase 2 Trial of Ponatinib in Participants With Metastatic and/or Unresectable Gastrointestinal Stromal Tumor

Phase 2 Trial of Ponatinib in Patients With Metastatic and/or Unresectable Gastrointestinal Stromal Tumor Following Failure of Prior Tyrosine Kinase Inhibitor Therapy

To assess clinical benefit rate in participants with KIT exon 11-mutant GIST.It is defined as the composite of complete response(CR),partial response(PR),and stable disease(SD) lasting \>=16 weeks per modified Response Evaluation Criteria In Solid Tumors(RECIST) 1.1 as a measure of disease control.CR is complete disappearance of all target lesions and non-target disease, with the exception of nodal disease.All nodes, both target and non-target, must decrease to normal (short axis \<10millimeter \[mm\]).No new lesions.PR is \>=30% decrease under baseline of the sum of diameters of all target lesions.The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions.No unequivocal progression of non-target disease.No new lesions.SD is not qualifying for CR,PR,Progressive Disease(PD).PD is \>=20% increase from the smallest prior sum of the longest diameter(SLD)and with \>=5mm absolute increase, or appearance of a new lesion.

To assess clinical benefit rate in participants with GIST that lacks KIT exon 11 mutations (Cohort B) and in the total participant population. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis \<10 millimeter \[mm\]). No new lesions. PR was defined as \>=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. SD was defined as not qualifying for CR, PR, PD.

PFS is defined as the duration of time from start of study drug administration to time of objective disease progression or death due to any cause, whichever may come first. To assess PFS in each cohort and in the total participant population.

ORR is defined as the composite of CR and PR per Response Evaluation Criteria in RECIST 1.1, assessed for each cohort and in the total participant population. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis \<10 mm). No new lesions. PR was defined as \>=30% decrease under baseline of the sum of diameters of all target lesions.

OS is defined as the time interval between the first dose of study drug to death due to any cause. Overall survival was analyzed using the Kaplan-Meier method.

Ariad Pharmaceuticals

At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Participants with KIT exon 11-mutant GIST ponatinib: 45 mg, taken orally once-daily.

Cohort A

Participants with GIST that lack KIT exon 11 mutations (Cohort B) ponatinib: 45 mg, taken orally once-daily.

Cohort B

Total

The ITT population included all participants who received any dose of ponatinib in the study.

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Weight

Height

The intention to treat (ITT) population included all participants who received any dose of ponatinib in the study.

Study is ongoing. Uncontrolled Study. Small participant population. Non-randomized.

Medical Director

The ITT population included all participants who received any dose of ponatinib in the study. The ITT population where data at specified time points was available.

Clinical Benefit Rate (CBR) in Cohort A

Clinical Benefit Rate (CBR) in Cohort B

Progression-free Survival (PFS)

Percentage of Participants With Objective Response Rate (ORR)

Overall Survival (OS)

Number of Participants With Physical Examination

Hypertension

Procedural hypotension

Pyrexia

Chills

Feeling of body temperature change

Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Sign Measurements

Albumin decreased

Alkaline phosphatase increased

Alanine aminotransferase (ALT) increased

Amylase

Absolute neutrophil count (ANC) decreased

Aspartate aminotransferase (AST) increased

Bicarbonate decreased

Bilirubin

Calcium decreased

Calcium increased

Creatinine increased

Glucose decreased

Glucose increased

Hemoglobin decreased

Lipase increased

Lymphocytes (ALC)/ lymphopenia

Phosphorus decreased

Platelets decreased

Potassium decreased

Potassium increased

Sodium decreased

Sodium increased

Triglycerides increased

White blood cells (WBC) decreased

Number of Participants With Worst Shift From Baseline Values to Post-baseline Values in Laboratory Parameters

Ejection Fraction Decreased

Atrial Fibrillation

Sinus Tachycardia

Cardiac Failure Congestive

Myocardial Ischaemia

Pericardial Effusion

Right Ventricular Dysfunction

Sinus Bradycardia

Number of Participants With TEAEs Related to Electrocardiogram (ECG) Findings

Congestive Cardiac Failure

Decreased Ejection Fraction

Pulmonary Oedema

Number of Participants With TEAEs Related to Echocardiography Parameter

TEAE

Number of Participants Reporting One or More TEAEs and Serious Adverse Event (SAE)

Data was not collected for Cmax,ss, since outcome measure was not planned to be analyzed.

Cmax, SS: Maximum Observed Plasma Concentration at Steady State for Ponatinib

Participants with KIT exon 11-mutant GIST ponatinib: 45 milligram (mg), taken orally once-daily.

Participants with gastrointestinal stromal tumors (GIST) that lack KIT exon 11 mutations (Cohort B) ponatinib: 45 mg, taken orally once-daily.

Overall Study

Children with measurable localized or metastatic wt-GIST

Adults with measurable localized or metastatic wt-GIST

Vandetanib administered orally once per day continuously using a 28 day cycle until disease progression or unacceptable toxicity

Vandetanib

Brigitte C Widemann, M.D.

Background:

-Some people with wild-type gastrointestinal stromal tumors (WT-GIST) have a deficiency in one of their proteins called succinate dehydrogenase (SDH). Vandetanib is a cancer drug that has been approved to treat thyroid cancer and has been used with some success in other tumors that have a similar loss of SDH. Researchers want to see if this drug can also decrease tumor growth in people with WT-GIST.

Objectives:

-To test whether the study drug will benefit people with WT-GIST.

Eligibility:

-Adults and children 3 years old and older with WT-GIST.

Design:

* Researchers will test participants tumor tissue to confirm it is the wild type of GIST.
* Participants will be screened with a medical history, physical exam, and blood tests. They will also have electrical recording of the heart (Eastern Cooperative Oncology Group (ECOG)) and scans of the tumor.
* Participants will take the study drug in 28-day cycles. Their doctor will decide how many cycles they can complete.

  * They will take the study drug once every day and record it in a diary.
  * On Day 14, they will also visit their doctor to look for side effects.
* Before cycles 2, 3 and 4, participants will have a physical exam, urine tests, blood pressure check, and blood tests. These tests will then be done periodically for as long as they are in the study.
* Before cycle 4, scans will be done to check the size of the cancer. Most of these will be repeated every 3-6 cycles.
* When they stop taking the study drug, participants will return to the clinic for a physical exam and blood tests.

Background:

* Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumor of the gastrointestinal tract, resistant to cytotoxic chemotherapy and radiation therapy. KIT and platelet derived growth factor receptor alpha (PDGFRA) mutations have been identified as tumor initiating events in 85% of adult patients with GIST, but 85% of GISTs in pediatric patients lack KIT and PDGFRA mutations (wild-type) and imatinib is not as effective in eliciting objective responses.
* Recent work in the Pediatric and Wild-Type (wt) GIST Clinic at the National Cancer Institute (NCI) led to the identification of succinate dehydrogenase (SDH) germline mutations in 12% patients with wt-GIST (6/34). SDH protein expression evaluated using immunohistochemistry (IHC) was markedly decreased or absent in 18/18 patients with pediatric wt-GIST. Thus the majority of wt-GIST are SDH-deficient. Vandetanib (ZACTIMA; ZD6474; AstraZeneca) is an oral small molecule antineoplastic drug that inhibits vascular endothelial growth factor receptor 2 (VEGFR2), estimated glomerular filtration rate (EGFR), and rearranged during transfection (RET)-dependent signaling. Preliminary preclinical data demonstrate marked growth inhibition of SDH-mutant/deficient renal cell carcinoma cell lines when treated with vandetanib.

Objective(s):

-Primary: To assess the clinical activity (radiographic response Response Evaluation Criteria in Solid Tumors (RECIST v1.1) of vandetanib in children and adults with wt-GIST using RECIST (v1.1).

Eligibility:

-Adults and children with measurable localized or metastatic wt-GIST confirmed in a Clinical Laboratory Improvement Amendments (CLIA) laboratory will be eligible for trial participation. Patients must have measurable disease by RECISTv1.1 and adequate organ function.

Design:

* This phase II trial will determine whether daily oral vandetanib is active in patients with wt-GIST. Vandetanib activity will be assessed primarily by radiographic response of measurable disease using RECISTv1.1.
* Vandetanib will be administered orally once daily continuously in the absence of toxicity or disease progression, using a 28-day cycle.
* Patients will be carefully monitored for toxicity and response. A small, optimal two-stage phase II design with a target response rate of 25% will be used. Nine evaluable patients will be enrolled initially. If 1 or more of the first 9 have a response, then accrual would continue until a total of 24 patients have enrolled. If there are 3 or more responses in 24 (12.5% or more) patients, then this would be sufficiently interesting activity to warrant further study.

Phase II Trial of Vandetanib in Children and Adults With Wild-Type Gastrointestinal Stromal Tumors

Phase II Trial of Vandetanib (ZD6474, Caprelsa(R) in Children and Adults With Wild-Type Gastrointestinal Stromal Tumors

Clinical activity will be assessed primarily by radiographic response of measurable disease using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete Response is disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \<10 mm. Partial Response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study); (Note: the appearance of one or more new lesions is also considered progressions). Stable Disease is neither sufficient shrinkage to qualify for Partial Response nor sufficient increase to qualify for Progressive Disease, taking as reference the smallest sum diameters while on study.

The count of participants with serious and non-serious adverse events was assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). 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.

Overall survival is defined as the date of on-study to the date of death from any cause or last follow up.

Progression free survival is defined as the time interval from start of treatment to documented evidence of disease progression. Disease progression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).

The maximum standardized uptake value (SUVmax) was used to measure the uptake of FDG-PET by the Gastrointestinal Tumors.

National Cancer Institute (NCI)

Principal Investigator

Initially patients 18 years and older at the time of enrollment on this study will start vandetanib at a fixed dose of 200 mg once daily (QD) for cycles 1, 2, and 3. One cycle = 28 days. If vandetanib was tolerated at 200mg daily the dose was increased to 300mg daily. Because of excessive toxicity at the 300mg daily dose the study was amended to maintain a dose of 200mg daily in patients 18 years and older after cycle 3.

200 mg Vandetanib Adult

Patients 18 years and older at the time of enrollment on this study will start vandetanib at a fixed dose of 200 mg once daily (QD) for cycles 1, 2, and 3. One cycle = 28 days.

If Vandetanib was well tolerated: Cycles ≥4: 300 mg/dose

300 mg Vandetanib Adult

Patients younger than 18 years of age at the time of enrollment were started at a dose of 100 mg/m\^2 based on a dosing nomogram with a planned increase in the dose to 150mg/m\^2/day after the third cycle if the drug was tolerated. One cycle = 28 days.

Dose Level 100mg/m^2 Vandetanib Pediatric

Age, Categorical

Not meeting definition for Hispanic or Latino

Mexican, Puerto Rican, Cuban, Central or So. Amer.

Black or African American

White

Asian

Race/Ethnicity, Customized

Dr. Brigitte Widemann

Number of Participants With a Clinical Activity-radiographic Response

Count of Participants With Serious and Non-serious Adverse Events

Percentage of Participants Overall Survival

Progression Free-Survival

Baseline

Day 3-6 of cycle 1

Data were only collected from patients \>/= 15 years of age.

Maximum Standardized Uptake Value (SUVmax) on Fluorodeoxyglucose Positron Emission Tomography (FDG-PET)

Blood and Lymph Conditions

Immune System Diseases

Symptoms and General Pathology

Lymphoma

Pancreatitis

Autoimmune Pancreatitis

Pancreatic Diseases

Pancreatitis, Chronic

Autoimmune Diseases

Chronic Disease

Disease Attributes

Lymphosarcoma

Chronic Graft Versus Host Disease

Central Nervous System Depressants

Anesthetics

General anesthesia or conscious sedation will be started and an upper endoscopic ultrasound will be inserted into the participants mouth and advanced to the site of the lesion. The lesion will be punctured by the ProCore needle, then the stylet is completely removed, and negative suction pressure is applied using a 10 ml syringe for 30 seconds while the needle is stationary with the target. Then, the needle is moved back and forth several times within the target, utilizing the fanning technique. Finally, suction is released by closing the lock of the syringe and the needle is removed.

The procedure will be done in the same manner with same endoscopic technique and method of tissue procurement. The only difference will be using the SharkCore needle to acquire tissue.

The use of the standard ProCore needle to acquire diagnostic tissue

EUS-FNB with ProCore needle

The use of new SharkCore needle to acquire diagnostic tissue

EUS-FNB with SharkCore needle

This is the standard needle used currently to procure tissue from lesions under endoscopic ultrasound guidance

ProCore needle

This is the new FDA approved needle for tissue procurement under endoscopic ultrasound guidance.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Multicenter Trial With PegLiposomal Doxorubicin and Carboplatin Combination Chemotherapy in Gynecological Sarcomas and Mixed Epithelial-Mesenchymal Tumors	NCT00815945	Mesenchymal Tum... Carcinosarcoma Leiomyosarcoma	PegLiposomal Do... Carboplatin	18 Years -	AGO Study Group
A Phase 2 Trial of Ponatinib in Participants With Metastatic and/or Unresectable Gastrointestinal Stromal Tumor	NCT01874665	GIST	Ponatinib	18 Years -	Takeda
Phase II Trial of Vandetanib in Children and Adults With Wild-Type Gastrointestinal Stromal Tumors	NCT02015065	GIST	Vandetanib	3 Years - 99 Years	National Institutes of Health Clinical Center (CC)
Evaluation of a New EUS Guided Biopsy Needle (SharkCore) Comparing to Standard EUS Needle (ProCore)	NCT02766842	Mesenchymal Tum... Autoimmune Panc... Lymphoma Solid Tumors	EUS-FNB with Pr... EUS-FNB with Sh... ProCore needle SharkCore needl...	18 Years - 100 Years	Johns Hopkins University

Spots Global Cancer Trial Database for mesenchymal tumor