Depsipeptide (Romidepsin) in Treating Patients With Metastatic or Unresectable Soft Tissue Sarcoma

NCT00112463 | Completed Phase 2 Results

• 5 other identifiers: NCI-2012-01037CCCWFU 711036319U10CA081851P30CA012197
• Study Type: interventional
• Target: 40
• Locations: 0 countries
• Sites: N/A

Brief Summary

This phase II trial studies how well depsipeptide (romidepsin) works in treating patients with metastatic or unresectable soft tissue sarcoma. Drugs used in chemotherapy, such as depsipeptide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

Conditions

Adult Alveolar Soft-part Sarcoma; Adult Angiosarcoma; Adult Epithelioid Sarcoma; Adult Extraskeletal Chondrosarcoma; Adult Extraskeletal Osteosarcoma; Adult Fibrosarcoma; Adult Leiomyosarcoma; Adult Liposarcoma; Adult Malignant Fibrous Histiocytoma; Adult Malignant Hemangiopericytoma; Adult Malignant Mesenchymoma; Adult Neurofibrosarcoma; Adult Rhabdomyosarcoma; Adult Synovial Sarcoma; Gastrointestinal Stromal Tumor; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Adult Soft Tissue Sarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma

Outcome Measures

Primary Outcomes (3)

• Objective Tumor Response (Complete and Partial)

  Objective tumor response was evaluated using the criteria proposed by the Response Evaluation Criteria In Solid Tumors (RECIST) Committee (JNCI 92(3):205-216,2000). Changes in only the largest diameter (unidimensional measurement) of the target lesions are used. A sum of the longest diameter (LD) for all target lesions was calculated and reported as the baseline sum LD. The baseline sum LD was used as reference by which to characterize the objective tumor response. Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum LD; Overall Response (OR) = CR + PR

  While on treatment - max of 16 months

• Time to Progression

  Progressive disease is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameters (LD) of target lesions, taking as reference the smallest sum LD recorded since treatment started, or a measurable increase in a non-target lesion, or the appearance of new lesions. Time to progression is the number of months from first treatment until the date of progression.

  Until disease progression - max of 48 months

• Toxicity as Assessed Using the Expanded Common Toxicity Criteria Version 3

  The outcome reported here is the number (%) of participants who experienced grade 3 or greater toxicity while on study. A summary of the individual toxicities can be found in the AE/SAE results.

  During treatment (max of 16 months) and for 1 month following treatment

Secondary Outcomes (1)

• Survival

  Max of 98 months

Study Arms (1)

Treatment (single-agent depsipeptide)

EXPERIMENTAL

Patients receive depsipeptide (romidepsin) 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. Patients achieving a complete response (CR) receive 6 additional courses beyond documentation of CR.

Drug: romidepsin

Interventions

romidepsin DRUG

DEP is administered at a dose of 13 mg/m2 as a 4-hour intravenous infusion in the outpatient setting.

Also known as: FK228, FR901228, Istodax

Treatment (single-agent depsipeptide)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed soft tissue sarcoma (STS), including, but not limited to, the following histologies:
• Gastrointestinal stromal tumors (GIST)
• Refractory to imatinib mesylate
• Desmoplastic small round cell tumors
• Clear cell sarcoma
• Extraskeletal osteosarcoma\*
• Extraskeletal Ewing's sarcoma\*
• Extraskeletal (myxoid) chondrosarcoma\*
• Secondary STS (e.g., radiation-induced STS or neurofibrosarcoma due to neurofibromatosis) allowed
• Metastatic or unresectable disease
• No standard curative therapy exists
• Patients with GIST must have received and progressed on imatinib mesylate
• Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan
• No known brain metastases
• Performance status - Eastern Cooperative Oncology Group (ECOG) 0-2

You may not qualify if:

• No cardiac abnormalities (e.g., congenital long QT syndrome)
• No myocardial infarction within the past year
• No history of coronary artery disease (e.g., angina Canadian Class II-IV or positive stress imaging study)
• No cardiac ischemia (ST depression \>2 mm) by electrocardiogram (ECG)
• No New York Heart Association Class II-IV congestive heart failure
• Ejection fraction \> 50% by multi gated acquisition scan (MUGA) scan or echocardiogram
• No history of sustained ventricular tachycardia, ventricular fibrillation, Torsades de Pointes, or cardiac arrest unless controlled by an automatic implantable cardioverter defibrillator
• No hypertrophic or restrictive cardiomyopathy from prior treatment or other causes
• No significant left ventricular hypertrophy
• No uncontrolled hypertension (i.e., blood pressure ≥ 160/95 mm Hg)
• No cardiac arrhythmia requiring anti-arrhythmic medication
• Beta blocker or calcium channel blocker allowed
• Patients on digitalis that cannot be discontinued not allowed
• No Mobitz II second degree block without a pacemaker (first degree or Mobitz I second degree block, bradyarrhythmias, or sick sinus syndrome require Holter monitoring and evaluation by cardiology)
• No uncontrolled dysrhythmia

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

MeSH Terms

Conditions

Sarcoma, Alveolar Soft Part; Hemangiosarcoma; Sarcoma; Chondrosarcoma, Extraskeletal Myxoid; Fibrosarcoma; Leiomyosarcoma; Liposarcoma; Histiocytoma, Malignant Fibrous; Hemangiopericytoma, Malignant; Malignant mesenchymal tumor; Neurofibrosarcoma; Rhabdomyosarcoma; Sarcoma, Synovial; Gastrointestinal Stromal Tumors; Neuroectodermal Tumors, Primitive, Peripheral

Interventions

romidepsin

Condition Hierarchy (Ancestors)

Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Vascular Tissue; Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue; Neoplasms, Adipose Tissue; Histiocytoma; Neurofibroma; Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Peripheral Nervous System Neoplasms; Nervous System Neoplasms; Nervous System Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases; Myosarcoma; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Glandular and Epithelial

Results Point of Contact

• Title: Dr. Doug Case
• Organization: Wake Forest School of Medicine

dcase@wakehealth.edu

336-716-1048

Study Officials

• Paul Savage

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2005
• First Posted: June 3, 2005
• Study Start: January 7, 2005
• Primary Completion: October 23, 2008
• Study Completion: October 23, 2008
• Last Updated: June 14, 2017
• Results First Posted: May 12, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will not share