Neoplasms

All Conditions

Symptoms and General Pathology

Digestive System Diseases

Gland and Hormone Related Diseases

Substance Related Disorders

Rare Diseases

Carcinoma

Adenoma

Recurrence

Neuroendocrine Tumors

Adenoma, Islet Cell

Carcinoid Tumor

Carcinoma, Islet Cell

Insulinoma

Gastrinoma

Glucagonoma

Somatostatinoma

Zollinger-Ellison Syndrome

Syndrome

Malignant Carcinoid Syndrome

Serotonin Syndrome

Gastrointestinal Neoplasms

Digestive System Neoplasms

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Gastrointestinal Diseases

Pancreatic Neoplasms

Endocrine Gland Neoplasms

Pancreatic Diseases

Endocrine System Diseases

Neuroendocrine Tumor

Pancreatic Neuroendocrine Tumor

Carcinoid Syndrome

Neuroepithelioma

Pancreatic Cancer

Antineoplastic Agents

All Drugs and Chemicals

Gastrointestinal Agents

Anti-Infective Agents

Capecitabine

Cisplatin

Pancreatic Polypeptide

Streptozocin

Antimetabolites

Anti-Bacterial Agents

Antibiotics, Antitubercular

capecitabine

cisplatin

streptozocin

DNA analysis

RNA analysis

protein analysis

proteomic profiling

laboratory biomarker analysis

Pippa Corrie, PhD, FRCP

Tim Meyer, MD, BSc, MRCP, PhD

RATIONALE: Drugs used in chemotherapy, such as capecitabine, streptozocin, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving capecitabine together with streptozocin is more effective with or without cisplatin in treating neuroendocrine tumors.

PURPOSE: This randomized phase II trial is studying giving capecitabine together with streptozocin to see how well it works compared with or without cisplatin in treating patients with unresectable or metastatic neuroendocrine tumors.

OBJECTIVES:

Primary

* To determine the objective response rate in patients with neuroendocrine tumors treated with capecitabine and streptozocin with or without cisplatin.

Secondary

* To determine the overall response rate, including both objective and biochemical responses, to these regimens.
* To determine the functional response to these regimens.
* To determine the toxicity of these regimens.
* To identify the optimal drug doses in each regimen to be recommended for a subsequent phase III trial.
* To determine the progression-free and overall survival of patients receiving these regimens.
* To determine the quality of life of these patients.
* To determine molecular markers predictive of response to chemotherapy.

OUTLINE: This is a multicenter study. Patients are stratified according to site of origin (known vs unknown primary site), prior antitumor treatment, tumor function (functional vs nonfunctional), and study center. Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive streptozocin IV over 2 hours on day 1 and oral capecitabine twice daily on days 1-21.
* Arm II: Patients receive cisplatin IV over 2 hours on day 1 and streptozocin and capecitabine as in arm I.

In both treatment arms, treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients complete the EORTC QLQC30 questionnaire and EORTC QLQ-GI.NET21 module for quality-of-life assessment at baseline, every 9 weeks during treatment, and at 12 weeks post-treatment.

Tumor tissue is obtained at baseline and assessed for Ki67 and mitotic index. Novel tissue-specific transcription factors (e.g., CDX2) are also assessed. Blood samples are collected at baseline and 9 weeks and examined by DNA, RNA, and proteomic analysis.

After completion of study therapy, patients are followed every 12 weeks.

Capecitabine and Streptozocin With or Without Cisplatin in Treating Patients With Unresectable or Metastatic Neuroendocrine Tumors

A Randomised Phase II Study Comparing Capecitabine Plus Streptozocin With or Without Cisplatin Chemotherapy as Treatment for Unresectable or Metastatic Neuroendocrine Tumors

Cambridge University Hospitals NHS Foundation Trust

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Carcinoma, Hepatocellular

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Carcinoma, Neuroendocrine

Cystadenocarcinoma, Serous

Carcinosarcoma

Mixed Tumor, Mullerian

Adenocarcinoma, Papillary

Fallopian Tube Neoplasms

Peritoneal Neoplasms

Cystadenocarcinoma

Carcinoma, Endometrioid

Adenoma, Pleomorphic

Liver Neoplasms

Intestinal Neoplasms

Stomach Neoplasms

Disease Attributes

Liver Diseases

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

Fallopian Tube Diseases

Abdominal Neoplasms

Peritoneal Diseases

Neoplasms, Cystic, Mucinous, and Serous

Endometrial Neoplasms

Uterine Neoplasms

Sarcoma

Neoplasms, Connective and Soft Tissue

Intestinal Diseases

Stomach Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Gastro-enteropancreatic Neuroendocrine Tumor

Fallopian Tube Cancer

Malignant Mixed Mullerian Tumor

Ovarian Carcinosarcoma

Uterine Carcinosarcoma

Adenocarcinoma of the Appendix

Stomach Cancer

Soft Tissue Sarcoma

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

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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Capecitabine and Streptozocin With or Without Cisplatin in Treating Patients With Unresectable or Metastatic Neuroendocrine Tumors	NCT00602082	Gastrointestina... Islet Cell Tumo...	capecitabine cisplatin streptozocin DNA analysis RNA analysis protein analysi... proteomic profi... laboratory biom...	18 Years -	National Cancer Institute (NCI)
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)

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