Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Lymphoma, T-Cell

Lymphoma, T-Cell, Peripheral

Lymphoma, Non-Hodgkin

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Peripheral T-cell Lymphoma

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Romidepsin

Anti-Bacterial Agents

Antibiotics, Antitubercular

Histone Deacetylase Inhibitors

Enzyme Inhibitors

Depsipeptide

Dr Johann De Bono

To evaluate the safety and tolerability of extended treatment with depsipeptide in patients who have at least demonstrated stable disease on prior Gloucester-sponsored depsipeptide clinical trials, and in the opinion of their physician/ investigator might benefit from continued treatment with depsipeptide

A Multicenter, Open-Label Continuation Trial Evaluating the Tolerability and Activity of Depsipeptide (FK228) in Patients That Have Completed a Prior Clinical Study With Depsipeptide.

Royal Marsden NHS Foundation Trust

Digestive System Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Symptoms and General Pathology

Esophageal Neoplasms

Carcinoma

Small Cell Lung Carcinoma

Carcinoma, Non-Small-Cell Lung

Neoplasm Metastasis

Lung Neoplasms

Mesothelioma

Mesothelioma, Malignant

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Adenoma

Neoplasms, Glandular and Epithelial

Neoplasms, Mesothelial

Pleural Neoplasms

Esophageal Cancer

Small Cell Lung Cancer

Malignant Mesothelioma

Anti-Inflammatory Agents

Antirheumatic Agents

Analgesics

Decitabine

Celecoxib

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Cyclooxygenase 2 Inhibitors

Cyclooxygenase Inhibitors

Antimetabolites

assigned dose level on day 4 and day 10 of each 34 day cycle

400mg PO BID on days 4 through 34 of each cycle

David S Schrump, M.D.

Background:

Previously we have demonstrated induction of tumor antigen and tumor suppressor gene expression in lung cancer cells following exposure to the DNA demethylating agent, Decitabine (DAC). We have also demonstrated that DAC mediated target gene expression and apoptosis can be significantly enhanced in cancer cells by subsequent exposure to the histone deacetylase (HDAC) inhibitor Depsipeptide FK228 (DP). Furthermore, we have demonstrated that following DAC, or DAC/DP exposure, cancer cells can be recognized by cytolytic T cells specific for the cancer testis antigen, NY-FSO-1.

This Phase I study will evaluate gene induction in thoracic oncology patients mediated by sequential DAC/DP treatment with or without the selective COX-2 inhibitor, celecoxib.

Objectives:

Evaluation of the pharmacokinetics and toxicity of continuous 72-hour intravenous Decitabine (DAC) infusion followed by 4-hour intravenous infusion of Depsipeptide FK228 (DP) with or without oral celecoxib in patients with unresectable cancers involving the lungs or pleura.

Analysis of NY-ESO-1, p16 and p21 expression in cancer specimens before and after sequential Decitabine/Depsipeptide treatment.

Analysis of serologic response to NY-ESO-1 before and after sequential drug treatment.

Analysis of apoptosis in tumor biopsies before and after sequential Decitabine/Depsipeptide treatment.

Refinement of laser capture microdissection and micro-array techniques for analysis of gene expression profiles in tumor tissues.

Eligibility:

Patients with histologically or cytologically proven primary small cell or non-small cell lung cancers, advanced esophageal cancers, pleural mesotheliomas, or non-thoracic cancers with metastases to the lungs or pleura.

Patients must be 18 years or older with an ECOG performance status of 0-2 and have adequate pulmonary reserve evidenced by FEV1 and DLCO greater than the 30% predicted, and less than 50 mm Hg and p02 greater than 60 mm Hg on room air ABG.

Patients must have a platelet count greater than 100.000. an ANC equal to or greater than 1500 without transfusion or cytokine support, a normal PT, and adequate hepatic function as evidenced by a total bilirubin of less than 1.5 x upper limits of normal. Serum creatinine less than or equal to 1.6 mg/ml or the creatinine clearance must be greater than 70 ml/min/1.73m(2).

Design:

Patients with inoperable malignancies involving lungs or pleura will receive two cycles of 72-hour intravenous infusion of Decitabine followed by 4-hour Depsipeptide infusion using a Phase I study design.

Decitabine will be administered by continuous infusion on days 1-4, and patient cohorts will receive escalating doses of Depsipeptide administered on day 4 and day 10 of a 34 day cycle.

Once the MTD and toxicities for sequential DAC/DP have been identified, additional cohorts of 6 lung cancer patients and 6 mesothelioma patients will receive sequential DAC/DP administered at the MTD as outlined above with celecoxib (400mg bid) administered on days 4-34 of each treatment cycle, as a means to enhance target cell apoptosis and facilitate anti-tumor immune recognition/response.

Pharmacokinetics, systemic toxicity, and response to therapy will be recorded. Tumor biopsies will be obtained prior to, and after therapy to evaluate expression of NY-ESO-1 tumor antigen, as well as p16 and p21 tumor suppressor genes, which are known to be modulated by chromatin structure. Additional analysis will be undertaken to evaluate the extent of apoptosis in tumor tissues, and to determine if immune recognition of NY-ESO-1 can be demonstrated following sequential DAC?DP +/- celecoxib treatment.

As the exact set of comparisons and analyses to be performed will be determined following completion of the trial and will be based on limited numbers of patients, the analyses will be considered exploratory and hypothesis generating rather than definitive.

A total of 40 patients will be enrolled.

Phase I Study of Gene Induction Mediated by Sequential Decitabine/Depsipeptide Infusion With or Without Concurrent Celecoxib in Subjects With Pulmonary and Pleural Malignancies

National Cancer Institute (NCI)

Nervous System Diseases

Recurrence

Glioblastoma

Glioma

Brain Neoplasms

Astrocytoma

Oligodendroglioma

Gliosarcoma

Disease Attributes

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Brain Tumor, Adult

Anaplastic Astrocytoma

Anaplastic Oligodendroglioma

Neuroepithelioma

Patients receive FR901228 (romidepsin) IV over 4 hours on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Dose escalation two dose levels:

Romidepsin (depsipeptide): 13.3mg/m2 and 17.7mg/m2

Pharmacokinetics

Patients receive FR901228 (romidepsin) as in phase I at dose level 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity

Romidepsin (depsipeptide): 13.3mg/m2

depsipeptide

Howard Fine, MD

This phase I/II trial is studying the side effects and best dose of FR901228 and to see how well it works in treating patients with recurrent high-grade gliomas. FR901228 may stop the growth of tumor cells by blocking the enzymes necessary for their growth

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose (MTD) of FR901228 (depsipeptide) in patients with recurrent malignant gliomas who are taking enzyme-inducing antiepileptic drugs (EIAEDs). (Phase I) II. Determine the safety profile of this drug in these patients. (Phase I) III. Determine the pharmacokinetics and pharmacodynamics of this drug in these patients. (Phase I) IV. Determine the clinical efficacy of this drug, as measured by 6-month progression-free survival and objective tumor response, in these patients. (Phase II) V. Determine the safety profile of this drug when administered at the phase I MTD concurrently with or without EIAEDs in these patients. (Phase II)

OUTLINE: This is a multicenter, phase I, dose-escalation study followed by a phase II study. Patients are stratified according to study phase (I vs II), concurrent use of enzyme-inducing anti-epileptic drugs (EIAEDs) (yes vs no), histology (recurrent glioblastoma multiforme/gliosarcoma vs recurrent anaplastic glioma), pre-operative candidacy (yes vs no), and measurable/evaluable disease (yes vs no). Patients are assigned to 1 of 2 treatment groups (group A: no EIAEDs or group B: concurrent use of EIAEDs).

Phase I (group B only): Patients receive FR901228 (depsipeptide) IV over 4 hours on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of FR901228 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of up to 6 patients experience dose-limiting toxicity.

Phase II (groups A and B):

Group A (phase II): Patients receive FR901228 as in phase I at dose level 1. Group B (phase II): Patients receive FR901228 as in phase I at the MTD.

FR901228 in Treating Patients With Recurrent High-Grade Gliomas

A Phase I-II Trial of Depsipeptide in Patients With Recurrent High-Grade Gliomas

dose limiting toxicity defined as: ANC \</=1000 or Platelets \<100K; SGOT \>/= 3X ULN and T. Bili \>/= 1.5 ULN

grade 3 Nausea, vomiting, fatigue and asymptomatic hypocalcemia (treatment may continue after discuss with PI)

evaluated patients with glioblastoma (GBM (35 patients)

RECIST Complete Response (CR): Complete disappearance of all measurable and evaluable disease. No new lesions. No evidence of non-evaluable disease. Patients must be on no steroids.

Partial Response (PR): Greater than or equal to 50% decrease under baseline in the sum of products of perpendicular diameters of all measurable lesions. No progression of evaluable disease. No new lesions.

Stable/No Response: Does not qualify for CR, PR, or progression. The designation of Stable/No Response requires a minimum of 8 weeks duration.

Progression: 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR clear clinical worsening or failure to return for evaluation due to death or deteriorating condition

in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only

Patients receive FR901228 (romidepsin) IV over 4 hours on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Dose escalation two dose levels:

Romidepsin (depsipeptide): 13.3mg/m2 and 17.7mg/m2

Pharmacokinetics

depsipeptide: Given IV

Phase 1 Dose Escalation - Romidepsin

Patients receive FR901228 (romidepsin) as in phase I at dose level 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity

Romidepsin (depsipeptide): 13.3mg/m2

depsipeptide: Given IV

Phase 2 Dose From Phase 1 - Romidepsin

Total

Age, Continuous

Gender

90-100

60-80

Higher score better 100 normal no complaints/disease 90 capable normal activity few symptoms/disease 80 normal activity, some difficulty some symptoms/signs 70 caring for self not capable normal activity/work 60 requiring some help can take care of most personal requirements 50 requires help often requires frequent medical care 40 disabled requires special care/help 30 severely disabled hospital admission indicated but no risk of death 20 very ill urgently requiring admission requires supportive measures/treatment 10 moribund rapidly progressive fatal disease processes 0 death

Karnofsky Performance Status Scale (KPS)

Anaplastic glioma

Gliobastoma

Histology

Prior Radiotherapy

Prior chemotherapy regimens

two patients were removed from the analysis due to one withdrawing consent and one was deemed ineligible.

Dose escalation was terminated after 2 dose levels because PK parameters of romidepsin in pts receiving EIAEDs were similar to those reported in Adults not receiving CYP34A inducing drugs, we wanted to avoid the expected dose limiting toxicity.

Number of Participants With Dose-limiting Toxicities Due to Romidepsin Graded According to the NCI Common Toxicity Criteria (CTCAE Version 3.0) (Phase I)

evaluation of patients with GBM histology

6 Months Progression-free Survival (Phase II)

Response Rate Associated With Depsipeptide Therapy (Phase II)

Overall Study

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

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

Depsipeptide administered on Days 1, 8, and15 of a 28-day cycle.

Gini Fleming, MD

RATIONALE: FR901228 may stop the growth of tumor cells by blocking the enzymes necessary for their growth.

PURPOSE: This phase II trial is studying how well FR901228 works in treating patients with relapsed or refractory advanced ovarian epithelial cancer.

OBJECTIVES:

Primary

* Determine the response rate (complete and partial) in patients with relapsed or refractory advanced ovarian epithelial carcinoma treated with FR901228 (depsipeptide).
* Determine the toxicity of this drug in these patients.

Secondary

* Correlate clinical response with platinum sensitivity in patients treated with this drug.
* Correlate clinical response with P-glycoprotein expression or p53 status in patients treated with this drug.

OUTLINE: This is multicenter study. Patients are stratified according to response to prior platinum administration (platinum resistant vs platinum sensitive).

Patients receive FR901228 (depsipeptide) IV over 4 hours on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 20-37 patients will be accrued for this study within 12 months.

FR901228 in Treating Patients With Relapsed or Refractory Advanced Ovarian Epithelial Cancer

A Phase II Study Of Depsipeptide In Patients With Relapsed Or Refractory Ovarian Carcinoma

University of Chicago

Heart and Blood Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Antiemetics

Gastrointestinal Agents

Dexamethasone

Bortezomib

Dexamethasone acetate

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Cohort 1. Dose escalation, IV, Weeklyx3 in a 4week cycle. Cohort 2A. 12mg/m2, IV, Weeklyx3 in a 4week cycle. Cohort 2B. 12mg/m2, IV, Weeklyx2 in a 3week cycle.

Cohort 1 and 2A. 3.5mg/m2, IV, day 1, 4, 8, 11 in 28 day cycle. Cohort 2B. 3.5mg/m2, IV, day 1, 4, 8, 11 in 21 day cycle

bortezomib

20mg for 2 days with each dose of bortezomib

dexamethasone

Joanne Dean

Sam Ruell

Alvin Milner

Simon J Harrison, MBBS, PhD.

Miles Prince, MD

The purpose of the first phase of the study is to determine whether, and at what dose, depsipeptide, bortezomib and dexamethasone can be safely administered to patients with Multiple Myeloma. The second phase of the study will establish whether depsipeptide, bortezomib and dexamethasone is effective in the treatment of patients with multiple myeloma. The study will also examine the role of maintenance therapy with depsipeptide.

Several groups have explored the possible synergistic interactions between proteasome and HDAC inhibitors in malignant hematopoietic cells. Bortezomib and HDACIs synergistically induce apoptosis, mitochondrial injury (via BAX), ROS generation and oxidative injury in human leukemia and myeloma cells.

In view of this evidence, we are proposing a trial to examine the clinical effects of combined romidepsin and bortezomib in patients with relapsed/refractory MM. However, there are currently no data as to whether these drugs are safe to administer in combination or at what dose toxicity they may become unacceptable.

Trial Design Open label, single centre, single arm, phase I/II dose escalation trial of bortezomib-dexamethasone with the addition of romidepsin followed by maintenance therapy until disease progression.

Primary objective:

• To determine the maximum tolerated dose (MTD) of romidepsin administered with Bortezomib in patients with relapsed multiple myeloma by the assessment of adverse events and abnormal laboratory values.

Primary endpoint:

• Toxicity evaluation at each of four dose levels presented in the dose-escalation schedule

Secondary objective:

• To determine the efficacy of this combination at the MTD in terms of (i) overall response, (ii) time to progression and (iii) overall survival

Secondary endpoints:

* Overall response (OR), defined as the best response on treatment based on M Protein response criteria with CR documented to EMBT standard and in conjunction with soft tissue plasmacytomas response criteria and corrected serum calcium level.
* Time to progression (TTP), defined as the time from commencement of treatment to the date of first evidence of progressive disease.
* Overall survival (OS), defined as the time from commencement of treatment to the date of death from any cause

A Phase I/II Trial of Romidepsin (Depsipeptide) and Bortezomib in Patients With Relapsed Myeloma

Celgene Corporation

Janssen-Cilag Ltd.

Peter MacCallum Cancer Centre, Australia

Simon Harrison/ Consultant Haematologist

Skin and Connective Tissue Diseases

Melanoma

Neuroendocrine Tumors

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Depsipeptide is administered as a 4-hour IV infusion weekly in doses of 13 mg/m\^2 for 3 weeks. Repeat cycle every 28 days until unacceptable toxicity or disease progression.

David H. Lawson, MD

RATIONALE: Drugs used in chemotherapy, such as FR901228, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This phase II trial is studying how well FR901228 works in treating patients with unresectable stage III or stage IV malignant melanoma.

OBJECTIVES:

Primary

* Determine the response rate in patients with unresectable stage III or stage IV malignant melanoma treated with FR901228 (depsipeptide).

Secondary

* Determine the progression-free and overall survival of patients treated with this drug.
* Determine the toxicity profile of this drug in these patients.

OUTLINE: This is a multicenter study.

Patients receive FR901228 (depsipeptide) intravenously (IV) over 4 hours on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 1 year.

PROJECTED ACCRUAL: A total of 22-40 patients will be accrued for this study within 18 months.

FR901228 in Treating Patients With Unresectable Stage III or Stage IV Malignant Melanoma

Phase II Trial of Depsipeptide (NSC 630176) in Advanced Malignant Melanoma

Response is evaluated using Solid Tumor Response Criteria (RECIST) and defined as either complete repose (CR) or partial response (PR).

Per RECIST criteria, CR = disappearance of all target and nontarget lesions; PR = at least 30% decrease in the sum of the longest diameters of target lesions from baseline, and persistence of one or more non-target lesion(s) and/or the maintenance of tumor marker level above the normal limits.

ECOG-ACRIN Cancer Research Group

Submission of late adverse events is required at follow-up visits up to 3 years .

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Multicenter, Open-Label Continuation Trial Evaluating the Tolerability and Activity of Depsipeptide (FK228) in Patients That Have Completed a Prior Clinical Study With Depsipeptide.	NCT00299351	Peripheral T Ce...	Depsipeptide	0 Years -	Royal Marsden NHS Foundation Trust
Phase I Study of Gene Induction Mediated by Sequential Decitabine/Depsipeptide Infusion With or Without Concurrent Celecoxib in Subjects With Pulmonary and Pleural Malignancies	NCT00037817	Advanced Esopha... Primary Small C... Non-Small-Cell ... Pleural Mesothe... Cancers of Non-...	Decitabine Depsipeptide Celecoxib	18 Years - 65 Years	National Institutes of Health Clinical Center (CC)
FR901228 in Treating Patients With Recurrent High-Grade Gliomas	NCT00085540	Adult Anaplasti... Adult Anaplasti... Adult Giant Cel... Adult Gliosarco... Recurrent Adult...	depsipeptide	18 Years -	National Cancer Institute (NCI)
FR901228 in Treating Patients With Relapsed or Refractory Advanced Ovarian Epithelial Cancer	NCT00085527	Ovarian Cancer	depsipeptide	18 Years -	University of Chicago
A Phase I/II Trial of Romidepsin (Depsipeptide) and Bortezomib in Patients With Relapsed Myeloma	NCT00431990	Multiple Myelom...	depsipeptide bortezomib dexamethasone	18 Years -	Peter MacCallum Cancer Centre, Australia
A Phase I/II Trial of Romidepsin (Depsipeptide) and Bortezomib in Patients With Relapsed Myeloma	NCT00431990	Multiple Myelom...	depsipeptide bortezomib dexamethasone	18 Years -	Peter MacCallum Cancer Centre, Australia
FR901228 in Treating Patients With Recurrent High-Grade Gliomas	NCT00085540	Adult Anaplasti... Adult Anaplasti... Adult Giant Cel... Adult Gliosarco... Recurrent Adult...	depsipeptide	18 Years -	National Cancer Institute (NCI)
FR901228 in Treating Patients With Unresectable Stage III or Stage IV Malignant Melanoma	NCT00104884	Malignant Melan... Melanoma	Depsipeptide	18 Years -	Eastern Cooperative Oncology Group
Depsipeptide/Flavopiridol Infusion for Cancers of the Lungs, Esophagus, Pleura, Thymus or Mediastinum	NCT00094978	Carcinoma, Smal... Carcinoma, Non-... Esophageal Neop... Mesothelioma	Depsipeptide Flavopiridol (a...	18 Years -	National Institutes of Health Clinical Center (CC)

Spots Global Cancer Trial Database for depsipeptide

Every month we try and update this database with for depsipeptide 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.