Neoplasms

All Conditions

Digestive System Diseases

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Substance Related Disorders

Rare Diseases

Carcinoma

Adenocarcinoma

Adenoma

Carcinoma, Hepatocellular

Recurrence

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Neuroendocrine Tumors

Carcinoma, Neuroendocrine

Cystadenocarcinoma, Serous

Carcinosarcoma

Mixed Tumor, Mullerian

Carcinoid Tumor

Carcinoma, Islet Cell

Insulinoma

Gastrinoma

Glucagonoma

Adenocarcinoma, Papillary

Somatostatinoma

Zollinger-Ellison Syndrome

Fallopian Tube Neoplasms

Peritoneal Neoplasms

Cystadenocarcinoma

Carcinoma, Endometrioid

Adenoma, Pleomorphic

Liver Neoplasms

Intestinal Neoplasms

Pancreatic Neoplasms

Stomach Neoplasms

Syndrome

Malignant Carcinoid Syndrome

Serotonin Syndrome

Gastrointestinal Neoplasms

Digestive System Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Disease Attributes

Gastrointestinal Diseases

Liver Diseases

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

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Fallopian Tube Diseases

Abdominal Neoplasms

Peritoneal Diseases

Neoplasms, Cystic, Mucinous, and Serous

Endometrial Neoplasms

Uterine Neoplasms

Sarcoma

Neoplasms, Connective and Soft Tissue

Adenoma, Islet Cell

Pancreatic Diseases

Intestinal Diseases

Stomach Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Neuroendocrine Tumor

Gastro-enteropancreatic Neuroendocrine Tumor

Fallopian Tube Cancer

Malignant Mixed Mullerian Tumor

Ovarian Carcinosarcoma

Uterine Carcinosarcoma

Adenocarcinoma of the Appendix

Pancreatic Cancer

Stomach Cancer

Carcinoid Syndrome

Neuroepithelioma

Soft Tissue Sarcoma

All Drugs and Chemicals

Antineoplastic Agents

Anti-Infective Agents

Hematinics

Antibodies

Antibodies, Monoclonal

Bevacizumab

Sirolimus

Immunoglobulins

Immunoglobulin G

Liver Extracts

Endothelial Growth Factors

Mitogens

Immunoglobulins, Intravenous

Temsirolimus

MTOR Inhibitors

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Immunologic Factors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Clotrimazole

Miconazole

Antifungal Agents

Immunosuppressive Agents

Protein Kinase Inhibitors

Enzyme Inhibitors

Patients receive temsirolimus IV on days 1, 8, 15, and 22, and bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Henry Pitot

This phase II trial studies how well temsirolimus and bevacizumab work in treating patients with advanced endometrial, ovarian, liver, carcinoid, or islet cell cancer. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of cancer by blocking blood flow to the tumor. Giving temsirolimus together with bevacizumab may kill more tumor cells.

PRIMARY OBJECTIVES:

I. To determine the response rate and progression-free survival at 6 months in patients with endometrial, ovarian, hepatocellular carcinoma, carcinoid or islet cell cancer.

II. To determine the toxicity of the combination of temsirolimus and bevacizumab in patients with endometrial, ovarian, hepatocellular carcinoma, carcinoid or islet cell cancer.

SECONDARY OBJECTIVES:

I. To collect blood and tumor specimens from all patients entered on the trial for possible future analysis.

OUTLINE:

Patients receive temsirolimus intravenously (IV) on days 1, 8, 15, and 22, and bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 3 years.

Temsirolimus and Bevacizumab in Treating Patients With Advanced Endometrial, Ovarian, Liver, Carcinoid, or Islet Cell Cancer

A Phase 2 Trial of Temsirolimus and Bevacizumab in Patients With Endometrial, Ovarian, Hepatocellular Carcinoma, Carcinoid or Islet Cell Cancer

Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. The 6-month progression free survival rate is the proportion of evaluable patients progression-free 6 months from registration. The 6-month progression-free rate is defined as the total number of efficacy evaluable patients on study without documentation of disease progression 6 months from registration divided by the total number of evaluable patients enrolled on study. Kaplan-Meier methodology will be used to estimate the final success proportion (i.e. progression free at 6 months with a 95% confidence interval).

Tumor response rate defined as the total number of efficacy-evaluable patients who achieved a complete or partial response according to the RECIST criteria divided by the total number of efficacy evaluable patients enrolled on study. Patients were evaluated using the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. In brief, a Complete Response (CR) means the complete disappearance of all target lesions and a reduction in each lymph node to \<1 cm. A Partial Response (PR) is defined as a 30% decrease in the sum of the longest diameter of the non-nodal target lesion from baseline. Each requires no new lesions present at evaluation. The proportion of participants with a response is provided here for each cohort. The proportion was calculated as the number of patients that had a best response of CR or PR divided by the number of patients evaluated for a response in each cohort.

Duration of response is defined for all evaluable patients who have achieved a response as the date at which the patient's objective status is first noted to be either a CR or PR to the date progression is documented. Objective response was assessed using Response Evaluation Criteria In Solid Tumors (RECIST) as described in Primary Objective 2 in this report. Median duration of response and the confidence interval for the median duration will be computed.

Adverse events are defined as events that are classified as either possibly, probably, or definitely related to study treatment, graded per National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0. The number of patients reporting grade 3 or higher adverse events at least possibly related to treatment are reported here. For a complete list of all reported adverse events, please see the adverse events section of this report.

Survival time will be defined as the time from registration to death. Time to event distributions will be estimated using the Kaplan-Meier method.

Time to progression is defined as the time from registration to disease progression. Patients who died without documentation of progression will be considered to have progressed on the date of their death. If a patient starts treatment and fails to return for evaluation, that patient will be censored for progression of disease at day one post-registration.

Time to treatment failure is defined as the time from study entry to the date patients end treatment.Time to treatment failure will be evaluated using the method of Kaplan-Meier.

National Cancer Institute (NCI)

Adverse events were collected at the end of each 28 day cycle for a maximum of 58 cycles.

Patients receive 25 mg temsirolimus IV on days 1, 8, 15, and 22, and 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Endometrial Cohort

Ovarian Cohort

Hepatocellular Cohort

Carcinoid Cohort

Islet Cell (Double Agent) Cohort

Patients receive 10 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Islet Cell (Bevacizumab-only) Cohort

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Canada

United States

Region of Enrollment

Henry Pitot, M.D.

All patients that received study treatment and were evaluated for response are included in this analysis

Progression Free Survival Rate

For this analysis, the number of patients that had a best response of CR or PR were divided by the number of patients evaluated for a response.

Tumor Response Rate

All patients that were assessed as a Complete Response or Partial Response were included in this analysis.

Duration of Response

Grade 3 Adverse Event

Grade 4 Adverse Event

Grade 5 Adverse Event

All patients that received protocol treatment and were evaluated for adverse events are reported in this analysis.

Incidence of Adverse Events

All patients that received study intervention and were followed for survival were included in this analysis.

Overall Survival

All patients that began protocol treatment and were evaluated for response are included in this analysis.

Time to Disease Progression

All patients that began study treatment were included in this analysis.

Time to Treatment Failure

Overall Study

Patients receive pazopanib hydrochloride PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO or MUGA during screening. Patients also undergo CT, MRI, and chest x-ray throughout the trial. Patients may optionally undergo blood sample collection during screening and on study.

Patients receive placebo PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. At the time of progressive disease, patients may cross-over to Arm I. Patients undergo ECHO or MUGA during screening. Patients also undergo CT, MRI, and chest x-ray throughout the trial. Patients may optionally undergo blood sample collection during screening and on study.

Biospecimen Collection

Computed Tomography

Echocardiography

Laboratory Biomarker Analysis

Magnetic Resonance Imaging

Multigated Acquisition Scan

Pazopanib Hydrochloride

Placebo Administration

Quality-of-Life Assessment

X-Ray Imaging

Emily K Bergsland

This randomized phase II trial studies how well pazopanib hydrochloride works in treating patients with carcinoid tumors that are growing, spreading, or getting worse. Pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVE:

I. For patients with progressive carcinoid tumors, progression-free survival (PFS defined by central review according to Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1) will be compared between patients randomized to treatment with pazopanib (pazopanib hydrochloride) versus placebo.

SECONDARY OBJECTIVES:

I. Overall survival (OS) will be compared between treatment arms. II. Objective response rate, duration of response, and time to treatment failure will be compared between treatment arms.

III. Progression free survival (PFS) as assessed by central radiology review and local radiology review will be compared overall and within treatment arms.

IV. Safety and tolerability of treatment with pazopanib/placebo will be evaluated within each treatment arm.

V. PFS and other indicators of efficacy will be estimated in patients who crossover to pazopanib from placebo.

VI. To determine the turn-around time for timely adjudicated central review. VII. To characterize the nature of discordance between local and central radiology review in assessment of progression.

VIII. To characterize the type and rate of progression in carcinoid (at study entry, on-study, and at progression).

IX. To develop new methods for modeling carcinoid growth and detecting treatment effects, and to perform simulations that advance new clinical trial designs to apply to future trials of carcinoid therapeutics.

X. To assess for differences in quality of life (QOL)-related domains between the two treatment groups (pazopanib versus placebo).

XI. To determine if the more brief measures of QOL-related domains provide comparable information to that which is provided by the longer assessments (European Organization for Research and Treatment of Cancer \[EORTC\], neuroendocrine tumors \[NET\]21).

XII. To provide validation data for the EORTC NET21 module in terms of responsiveness over time and differences across arms.

XIII. To determine whether components of the plasma angiome panel that have been shown to be predictive previously (interleukin-6 \[IL-6\] and vascular endothelial growth factor \[VEGF\]-D) are predictive of a therapeutic advantage for pazopanib treatment in baseline samples from the patients treated on A021202.

XIV. To determine whether other components of the plasma angiome panel tested (not IL-6 and VEGF-D) are predictive of a therapeutic advantage for pazopanib treatment in baseline samples from the patients treated on A021202.

XV. To evaluate the changes in the plasma angiome markers after treatment with or without pazopanib over time.

EXPLORATORY OBJECTIVES:

I. PFS at 6 months will be estimated within each treatment arm. II. Biochemical response (for chromogranin A, defined as a decrease of 50% or more in chromogranin A levels from baseline and for 5-hydroxyindoleacetic acid \[5-HIAA\], defined as a decrease of 50% or more in urinary 5-HIAA levels from baseline) will be compared between treatment arms among patients with elevated baseline levels of chromogranin A (CGA) and 5-HIAA.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive pazopanib hydrochloride orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) during screening. Patients also undergo computed tomography (CT), magnetic resonance imaging (MRI), and chest x-ray throughout the trial. Patients may optionally undergo blood sample collection during screening and on study.

ARM II: Patients receive placebo PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. At the time of progressive disease, patients may cross-over to Arm I. Patients undergo ECHO or MUGA during screening. Patients also undergo CT, MRI, and chest x-ray throughout the trial. Patients may optionally undergo blood sample collection during screening and on study.

After completion of study treatment, patients are followed up every 3-6 months for 5 years.

Pazopanib Hydrochloride in Treating Patients With Progressive Carcinoid Tumors

Prospective Randomized Phase II Trial of Pazopanib (NSC #737754) Versus Placebo in Patients With Progressive Carcinoid Tumors

Kaplan-Meier methods will be used including calculations of 95% confidence intervals.

Biochemical response (for chromogranin A, defined as a decrease of 50% or more in chromogranin A levels from baseline, and for 5-hydroxyindoleacetic acid \[5-HIAA\], defined as a decrease of 50% or more in urinary 5-HIAA levels from baseline) will be compared between treatment arms among patients with elevated baseline levels of serum chromogranin A (CGA) and 5-HIAA.

PFS will be measured from date of patient entry until documented progression of disease as determined by central review or death from any cause. If a patient does not have a documented date of progression or death, then PFS will be censored at the date of last adequate assessment. PFS will be estimated within treatment arm using the Kaplan-Meier method. Progression is defined as any new lesion or increase by ≥20% of previously involved sites from nadir based on RECIST criteria.

The best response per RECIST 1.1 criteria of participants receiving randomized treatment assignment. Complete response (CR): Disappearance of all evidence of disease, Partial response (PR): Regression of measurable disease and no new sites, Stable disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum diameters while on study. Progressive disease (PD): Any new lesion or increase by ≥20% of previously involved sites from nadir. Note that those considered evaluable for best response here were those who had disease measurements while on treatment. Those who discontinued therapy early prior to a disease evaluation were not included.

Overall survival (OS) will be measured from randomization until death from any cause. A patient who is alive at the time of the statistical analysis will be considered censored at the last date of known contact. OS will be estimated by the Kaplan-Meier method within each treatment arm.

Duration of response is defined as the time from documented response to time of progression and/or death. This time-to-event outcome will be summarized descriptively using the methods of Kaplan and Meier to characterize the cohort and distribution of this outcome.

Time to treatment failure is defined as the time from randomization to the time that treatment is terminated, including the reasons of disease progression, adverse events, withdrawal from study, or death. This time-to-event outcome will be evaluated using the methods of Kaplan and Meier.

Patients receive 800 mg pazopanib hydrochloride PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Arm I (Pazopanib Hydrochloride)

Patients receive 800 mg placebo PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. At the time of progressive disease, patients may cross-over to Arm I.

Arm II (Placebo)

Participants in Arm II (Placebo) who crossed over to receive pazopanib hydrochloride.

Placebo Crossover

Race (White vs Non-White)

Race/Ethnicity, Customized

Eastern Cooperative Oncology Group PS Scale: 0)Fully active, able to carry on all pre-disease performance without restriction; 1)Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work; 2)Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours; 3)Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours; 4)Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair.

ECOG Performance status

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Temsirolimus and Bevacizumab in Treating Patients With Advanced Endometrial, Ovarian, Liver, Carcinoid, or Islet Cell Cancer	NCT01010126	Adult Hepatocel... Advanced Adult ... Endometrial Ser... Localized Non-R... Lung Carcinoid ... Malignant Pancr... Malignant Pancr... Malignant Pancr... Malignant Pancr... Metastatic Dige... Ovarian Carcino... Ovarian Endomet... Ovarian Seromuc... Ovarian Serous ... Pancreatic Alph... Pancreatic Beta... Pancreatic Delt... Pancreatic G-Ce... Pancreatic Poly... Recurrent Adult... Recurrent Diges... Recurrent Fallo... Recurrent Ovari... Recurrent Pancr... Recurrent Prima... Recurrent Uteri... Regional Digest... Stage IIIA Fall... Stage IIIA Ovar... Stage IIIA Prim... Stage IIIA Uter... Stage IIIB Fall... Stage IIIB Ovar... Stage IIIB Prim... Stage IIIB Uter... Stage IIIC Fall... Stage IIIC Ovar... Stage IIIC Prim... Stage IIIC Uter... Stage IV Fallop... Stage IV Ovaria... Stage IV Primar... Stage IVA Uteri... Stage IVB Uteri... Uterine Carcino...	Bevacizumab Temsirolimus	18 Years -	National Cancer Institute (NCI)
Pazopanib Hydrochloride in Treating Patients With Progressive Carcinoid Tumors	NCT01841736	Foregut Neuroen... Hindgut Neuroen... Metastatic Dige... Metastatic Neur... Midgut Neuroend... Neuroendocrine ... Recurrent Diges... Regional Digest...	Biospecimen Col... Computed Tomogr... Echocardiograph... Laboratory Biom... Magnetic Resona... Multigated Acqu... Pazopanib Hydro... Placebo Adminis... Quality-of-Life... X-Ray Imaging	18 Years -	National Cancer Institute (NCI)
Pazopanib Hydrochloride in Treating Patients With Progressive Carcinoid Tumors	NCT01841736	Foregut Neuroen... Hindgut Neuroen... Metastatic Dige... Metastatic Neur... Midgut Neuroend... Neuroendocrine ... Recurrent Diges... Regional Digest...	Biospecimen Col... Computed Tomogr... Echocardiograph... Laboratory Biom... Magnetic Resona... Multigated Acqu... Pazopanib Hydro... Placebo Adminis... Quality-of-Life... X-Ray Imaging	18 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for recurrent digestive system neuroendocrine tumor g1