Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Symptoms and General Pathology

Rare Diseases

Carcinoma

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Disease Progression

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

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

Ovarian Cancer

Ovarian Epithelial Cancer

Antineoplastic Agents

Antirheumatic Agents

Dermatologic Agents

Reproductive Control Agents

All Drugs and Chemicals

Anti-Inflammatory Agents

Analgesics

Micronutrients

Hematinics

Vitamins

Methotrexate

Angiogenesis Inhibitors

Celecoxib

Cyclophosphamide

Antimetabolites

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Immunosuppressive Agents

Immunologic Factors

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Cyclooxygenase 2 Inhibitors

Cyclooxygenase Inhibitors

Antineoplastic Agents, Alkylating

Alkylating Agents

Folinic Acid

Folate

Vitamin B9

Maintenance Treatment for Ovary Carcinoma by Metronomic Chemotherapy

Metronomic Chemotherapy as maintenance treatment for patients with Ovarian Cancer

* Cytophosphan tab 50 mg -1x1 per day, continuous
* Celecoxib tab 200 mg - 1x2 per day, continuous
* Methotrexate tab 2.5 mg - 1x2 per day, 2 days weekly

Cytophosphan, Celecoxib, Methotrexate

David Loven, M.D.

Preclinical studies showed that metronomic chemotherapy can induce tumor regression secondary to apoptosis of the tumor blood vessels. This effect was increased by combining metronomic chemotherapy with anti-angiogenic drugs. Metronomic chemotherapy has already proved clinical effects too, especially on patients with breast or prostate carcinoma. This study is aimed to test the efficacy of an experimental metronomic chemotherapy regimen in a cohort of patients with ovarian cancer. Patients will receive the proposed regimen as maintenance treatment following response induction by the conventional maximal tolerated dose (MTD) regimen of Carboplatin and Paclitaxel. Our regimen will include Cytophosphan combined with two agents which are expected to act as indirect angiogenic inhibitors: (a) celecoxib, as a selective COX-2 inhibitor and (b) low-dose Methotrexate, as successfully practiced for suppressing the inflammatory manifestations of rheumatoid arthritis. All components of our regimen will be administered orally and continuously for one year based on the hypothesis that its anti-angiogenic properties will be able to suppress the recovery of residual disease, thus extending the time to progression (TTP), and possibly the overall survival as well.

Maintenance Treatment for Ovarian Carcinoma in Remission by an Antiangiogenic Treatment Strategy

Maintenance Treatment for Ovarian Carcinoma in Remission by an Antiangiogenic Treatment Strategy With Metronomic/Oral Chemotherapy (Cytophosphan Combined With Low-dose Methotrexate)and COX-2 Inhibition (Celecoxib)

Median time to progression of the cohort will be compared with equivalent measure in the literature.

HaEmek Medical Center, Israel

Blood and Lymph Conditions

Immune System Diseases

Nervous System Diseases

Leukemia

Neuroblastoma

Sarcoma

Lymphoma

Central Nervous System Neoplasms

Nervous System Neoplasms

Neuroectodermal Tumors, Primitive, Peripheral

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Neuroepithelial

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Soft Tissue Sarcoma

Lymphosarcoma

Neuroepithelioma

Anti-Infective Agents

Lipid Regulating Agents

Thalidomide

Etoposide

Etoposide phosphate

Fenofibrate

Anti-Bacterial Agents

Growth Inhibitors

Hypolipidemic Agents

Thalidomide: Start at 3 mg/kg (rounded to nearest 50 mg), increasing dose weekly by 50 mg as tolerated to 24 mg/kg (max 1,000 mg); Celecoxib: \< 20 kg at 100 mg; 20-50 kg at 200 mg; \> 50 kg at 400 mg; Fenofibrate: 90 mg/m2 (max 200 mg); Etoposide: 50 mg/m2; Cyclophosphamide: 2.5 mg/kg (max 100 mg); Patients receive oral etoposide once daily on days 1-21 and 43-63 (weeks 1-3 and 7-9) and oral cyclophosphamide once daily on days 22-42 (weeks 4-6). Patients also receive oral thalidomide once daily, oral celecoxib twice daily, and oral fenofibrate once daily in weeks 1-9. Treatment repeats approximately every 9 weeks for at least 3 courses in the absence of disease progression or unacceptable toxicity. Patients receive alternating etoposide and cyclophosphamide pulses (i.e., etoposide-cyclophosphamide-etoposide during courses 1 and 3 and cyclophosphamide-etoposide-cyclophosphamide during course 2).

celecoxib

cyclophosphamide

etoposide

fenofibrate

thalidomide

Mark W. Kieran, MD, PhD

RATIONALE: Drugs used in chemotherapy, such as etoposide and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Thalidomide, celecoxib, and fenofibrate may stop the growth of cancer cells by blocking blood flow to the cancer. Celecoxib also may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving combination chemotherapy together with thalidomide, celecoxib, and fenofibrate may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving etoposide and cyclophosphamide together with thalidomide, celecoxib, and fenofibrate works in treating young patients with relapsed or progressive cancer.

OBJECTIVES:

Primary

* Evaluate the activity of etoposide, cyclophosphamide, thalidomide, celecoxib, and fenofibrate, in terms of prolonging the time to disease progression, in young patients with relapsed or progressive cancer.

Secondary

* Determine, preliminarily, the biologic activity of this regimen, in terms of tumor response and overall survival, in these patients.
* Determine the toxicity of this regimen in these patients.
* Evaluate different radiographic techniques as markers of tumor response in these patients.
* Evaluate the predictive ability of in vitro correlative studies as markers of tumor response.

STATISTICAL DESIGN: Patients were classified into one of 8 strata according to diagnosis: leukemia/lymphoma, bone tumors, neuroblastoma, high grade glial tumors, low grade glial tumors, ependymoma, medulloblastoma/PNET, and miscellaneous. A two-stage design for each disease stratum was planned. The accrual goal at the end of the two-stage design was 20 subjects for each stratum. A stopping rule was applied after the accrual of the first 10 eligible subjects enrolled in each disease stratum. If 1 or more patients in the first 10 evaluable patients were alive and progression-free at 27 weeks and have tolerated therapy then accrual to stage two would proceed. Among 20 patients within a stratum, if 3 or more patients met primary endpoint then regimen would be considered successful. The probability of concluding the treatment is feasible is 0.95 if true success rate is 30% and 0.07 if true succes rate is 5%. Overall accrual target was 80-160 patients. Please see published manuscript (Robison et al Pediatr Blood Cancer 2014) for results within disease strata.

Etoposide, Cyclophosphamide, Thalidomide, Celecoxib, and Fenofibrate in Relapsed or Progressive Cancer

Anti-Angiogenic Chemotherapy: A Phase II Trial of the Oral 5-Drug Regimen (Thalidomide, Celecoxib, Fenofibrate, Etoposide and Cyclophosphamide) in Patients With Relapsed or Progressive Cancer

Proportion of patients alive at 27 weeks without progressive disease (PD) and having tolerated therapy. As appropriate for tumor type and location, gadolinium-enhanced MRI and other imaging modalites were used to assess response. Progressive disease was defined as \>/=25% increase in product of diameters, development of new areas of disease, or disease-attributable clinical deterioration or death, progressive disease. For patients with leukemia PD was defined as \>/=25% or \>/=5,000 cells/mm3 increase in number of circulating cells, development of extramedullary disease, or other clinical evidence of progression.

27-week progression-free survival is the probability of patients remaining alive and progression-free at 27-weeks from study entry estimated using Kaplan-Meier methods. As appropriate for tumor type and location, gadolinium-enhanced MRI and other imaging modalites were used to assess response. Progressive disease was defined as \>/=25% increase in product of diameters, development of new areas of disease, or disease-attributable clinical deterioration or death, progressive disease. For patients with leukemia PD was defined as \>/=25% or \>/=5,000 cells/mm3 increase in number of circulating cells, development of extramedullary disease, or other clinical evidence of progression.

27-week overall survival is the probability of patients remaining alive at 27-weeks from study entry estimated using with Kaplan-Meier methods.

As appropriate for tumor type and location, gadolinium-enhanced MRI and other imaging modalites were used to assess response. Best response was regarded as best response at any single assessment. Response was defined as follows: complete resolution of all demonstrable tumor, complete response (CR); \>/=50% decrease in the product of the 2 maximum perpendicular diameters relative to the baseline evaluation, partial response (PR); \<50% decrease and \<25% increase in product of diameters, stable disease (SD); and \>/=25% increase in product of diameters, development of new areas of disease, or disease-attributable clinical deterioration or death, progressive disease (PD). For patients with leukemia PD was defined as \>/=25% or \>/=5,000 cells/mm3 increase in number of circulating cells, development of extramedullary disease, or other clinical evidence of progression.

National Cancer Institute (NCI)

Boston Children's Hospital

Dana-Farber Cancer Institute

Principal Investigator

5-drug Metronomic Antiangiogenic Regimen

5-drug Metronmic Antiangiogenic Regimen

Age, Categorical

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

High Grade Glioma

Ependymoma

Low Grade Glioma

Bone Tumors

Medulloblastoma/PNET

Leukemia/Lymphoma

Miscellaneous CNS Tumors

Miscellaneous non-CNS Tumors

Patients were stratified within 7 disease strata and an 8th 'miscellaneous' stratum.

Disease Group

The analysis population represents patients who started treatment.

Mark Kieran

The analysis dataset is comprised of all treated patients.

Therapy Completion Rate

27-Week Progression-Free Survival

27-Week Overall Survival

Complete Response

Partial Response

Stable Disease

Progressive Disease

Not Evaluable

Best Response

Overall Study

Recurrence

Medulloblastoma

Disease Attributes

Glioma

Cytarabine

Bevacizumab

Fenofibric acid

Antineoplastic Agents, Immunological

Antiviral Agents

Anticholesteremic Agents

10mg/kg, intravenous (iv), biweekly, 1 year

35-50 mg/m2, oral, alternating 21-day cycles of daily oral etoposide and cyclophosphamide, 1 year

2.5mg/kg, oral, alternating 21-day cycles of daily oral etoposide and cyclophosphamide, 1 year

0.5mg, intrathecal, day 1-5, every four weeks, alternating with intrathecal liposomal cytarabine, 1 year

16-30mg, intrathecal, twice weekly for two weeks out of every four weeks, alternating with intrathecal etoposide phosphate, 1 year

Andreas Peyrl, MD

Irene Slavc, MD

Rebecca Loret de Mola

Rebecca Loret De Mola, MD

Ashley Ratcliffe

Virginia Harrod, MD

Elisabeth Hulla-Gumbsch

Martin Benesch, MD

Yvonne Ennemoser, MSc

Roman Crazzolara, MD

Martina Winkler

Georg Ebetsberger, MD

Neil Jones, MD

Agnes Gamper, MD

Alexandra Martincekova, MD

Jaroslav Sterba, MD

Zdenek Pavelka, MD

Klara Hruba

David Sumerauer, MD

Karsten Nysom, MD

Pierre Leblond, MD

Ingrid Torsvik

Ingrid Torsvik, MD

Alvaro Lassaletta, MD, PhD

Karin Fritzson

Anna Schröder- Håkansson

Magnus Sabel, MD

Birgitta Lannering, Prof

Birgitta Hellström

Pernilla Augustsson

Irene Devenney, MD

Yvonne Håkansson

Simon Johansson

Helena Mörse, MD

Carina Rinaldo

Yvonne Copeland

Stefan Holm, MD

Marita Wikström-Larsson

Mattias Mattsson

Katarina Vallin

Anders Öberg, MD

Monika Chocholous, MD

Patients with relapsed medulloblastoma, ependymoma and ATRT have a very poor prognosis whether treated with conventional chemotherapy, high-dose chemotherapy with stem cell rescue, irradiation or combinations of these modalities. Antiangiogenetic therapy has emerged as new treatment option in solid malignancies. The frequent, metronomic schedule targets both proliferating tumor cells and endothelial cells, and minimizes toxicity. In this study the investigators will evaluate the use of biweekly intravenous bevacizumab in combination with five oral drugs (thalidomide, celecoxib, fenofibrate, and alternating cycles of daily low-dose oral etoposide and cyclophosphamide), augmented with alternating courses of intrathecal etoposide and cytarabine. The aim of the study is to extend therapy options for children with recurrent or progressive medulloblastoma, ependymoma and ATRT, for whom no known curative therapy exists, by prolonging survival while maintaining good quality of life. The primary objective of the MEMMAT trial is to evaluate the activity of this multidrug antiangiogenic approach in these heavily pretreated children and young adults. Additionally, progression-free survival (PFS), overall survival (OS), as well as feasibility and toxicity will be examined.

3 Strata (medulloblastoma - 40 patients; ependymoma - 30 patients; ATRT - 30 patients)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Maintenance Treatment for Ovarian Carcinoma in Remission by an Antiangiogenic Treatment Strategy	NCT01175772	Ovarian Carcino...	Cytophosphan, C...	20 Years - 80 Years	HaEmek Medical Center, Israel
Etoposide, Cyclophosphamide, Thalidomide, Celecoxib, and Fenofibrate in Relapsed or Progressive Cancer	NCT00357500	Central Nervous... Leukemia Lymphoma Neuroblastoma Sarcoma Unspecified Chi...	celecoxib cyclophosphamid... etoposide fenofibrate thalidomide	- 21 Years	Dana-Farber Cancer Institute
Maintenance Treatment for Ovarian Carcinoma in Remission by an Antiangiogenic Treatment Strategy	NCT01175772	Ovarian Carcino...	Cytophosphan, C...	20 Years - 80 Years	HaEmek Medical Center, Israel
Antiangiogenic Therapy for Children With Recurrent Medulloblastoma, Ependymoma and ATRT	NCT01356290	Medulloblastoma... Ependymoma Recu... ATRT Recurrent	Bevacizumab Thalidomide Celecoxib Fenofibric acid Etoposide Cyclophosphamid... Etoposide phosp... Cytarabine	- 19 Years	Medical University of Vienna
Metronomic Temozolomide in Unfit NENs Patients Metronomic Temozolomide in Unfit Patients With Advanced Neuroendocrine Neoplasms (NENs): MeTe Study	NCT05554003	Neuroendocrine ... Frailty Chemotherapy Ef...	Temozolomide ca...	18 Years -	European Institute of Oncology
Antiangiogenic Therapy for Children With Recurrent Medulloblastoma, Ependymoma and ATRT	NCT01356290	Medulloblastoma... Ependymoma Recu... ATRT Recurrent	Bevacizumab Thalidomide Celecoxib Fenofibric acid Etoposide Cyclophosphamid... Etoposide phosp... Cytarabine	- 19 Years	Medical University of Vienna

Spots Global Cancer Trial Database for metronomic

Every month we try and update this database with for metronomic cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for metronomic

Every month we try and update this database with for metronomic cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for metronomic cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.