A Phase 2 interventional study of vorinostat and bortezomib in Recurrent Adult Soft Tissue Sarcoma, Stage III Adult Soft Tissue Sarcoma and Stage IV Adult Soft Tissue Sarcoma, sponsored by National Cancer Institute (NCI). Completed at 6 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2014-05-14.
Sponsored by National Cancer Institute (NCI) · Phase 2, Interventional, and Treatment
This phase II trial is studying how well giving vorinostat together with bortezomib works in treating patients with advanced soft tissue sarcoma. Vorinostat and bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving vorinostat together with bortezomib may kill more tumor cells.
PRIMARY OBJECTIVES:
I. To determine the objective response rate in patients with advanced soft tissue sarcoma treated with vorinostat and bortezomib.
SECONDARY OBJECTIVES:
I. Characterize the toxicity of this regimen in these patients. II. Evaluate the progression-free survival and median overall survival of patients treated with this regimen.
OUTLINE:
Patients receive vorinostat orally (PO) once daily on days 1-14. Patients also receive bortezomib intravenously (IV) over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study therapy, patients are followed up every 6 months for up to 2 years. (As of Addendum 7, patient follow-up no longer required.)
1,667 studies on the registry are indexed under Sarcoma; 393 are open to participants now.
This study's enrollment of 16 is below the median of 40 across 1,283 interventional studies indexed under Sarcoma.
Browse Sarcoma studies →National Cancer Institute (NCI) is the lead sponsor of 3,506 studies on the registry; 334 are open to participants now.
Of its 402 completed or terminated interventional studies of FDA-regulated products, 365 (91%) have results posted.
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Inclusion Criteria:
No small round cell tumors, including the following:
No known active and/or untreated brain metastases and/or brain metastases requiring ongoing therapy (e.g., corticosteroids)
No concurrent uncontrolled illness including, but not limited to, any of the following:
No more than 1 prior systemic treatment for advanced STS, including investigational agents
More than 4 weeks since prior and no concurrent chemotherapy (> 6 weeks for nitrosoureas or mitomycin C) or radiotherapy and recovered
No concurrent category I medications that are generally accepted to have a risk of causing Torsades de Pointes, including any of the following:
Patients receive 400 mg vorinostat orally once daily on days 1-14. Patients also receive 1.3 mg/m\^2 bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Drug: vorinostat · Drug: bortezomib
400 mg given PO
Also known as: L-001079038, SAHA, suberoylanilide hydroxamic acid, Zolinza
1.3 mg/m\^2 given IV
Also known as: LDP 341, MLN341, VELCADE
Confirmed Tumor Responses
The number of confirmed tumor responses is defined as a complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) on two consecutive evaluations at least six weeks apart. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the longest dimension (LD) of target lesions taking as reference the baseline sum LD.
Time frame: Up to 2 years
Progression Free Survival
Progression-free survival is defined as the time from registration to the time of progression or death, whichever comes first. The distribution and median of progression-free survival times will be estimated using the method of Kaplan-Meier.
Time frame: Up to 2 years
Overall Survival
The distribution of survival time will be estimated using the method of Kaplan-Meier.
Time frame: Time from registration to death due to any cause, assessed up to 2 years
Sixteen patients were accrued to this study from June 2009 through July 2010.
| Milestone | Treatment (Vorinostat, Bortezomib) |
|---|---|
| Started | 16 |
| Completed | 14 |
| Not completed | 2 |
| Withdrew: Protocol violation | 2 |
The number of confirmed tumor responses is defined as a complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) on two consecutive evaluations at least six weeks apart. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the longest dimension (LD) of target lesions taking as reference the baseline sum LD.
| participants | Treatment (Vorinostat, Bortezomib) |
|---|---|
| Complete Response (CR) | 0 |
| Partial Response (PR) | 0 |
Progression-free survival is defined as the time from registration to the time of progression or death, whichever comes first. The distribution and median of progression-free survival times will be estimated using the method of Kaplan-Meier.
| months | Treatment (Vorinostat, Bortezomib) |
|---|---|
| Progression Free Survival | 1.5 (1.3 to 2.9) |
The distribution of survival time will be estimated using the method of Kaplan-Meier.
| months | Treatment (Vorinostat, Bortezomib) |
|---|---|
| Overall Survival | 16.4 (9.4 to NA) |
Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Treatment (Vorinostat, Bortezomib) | — | 6/16 (37.5%) | 16/16 (100%) |
| Event | Treatment (Vorinostat, Bortezomib) |
|---|---|
| DiarrheaGastrointestinal disorders | 3/16 |
| Platelet count decreasedInvestigations | 3/16 |
| VomitingGastrointestinal disorders | 2/16 |
| Hemoglobin decreasedBlood and lymphatic system disorders | 1/16 |
| NauseaGastrointestinal disorders | 1/16 |
| FatigueGeneral disorders | 1/16 |
| INR increasedInvestigations | 1/16 |
| AnorexiaMetabolism and nutrition disorders | 1/16 |
| DehydrationMetabolism and nutrition disorders | 1/16 |
| Depressed level of consciousnessNervous system disorders | 1/16 |
| Event | Treatment (Vorinostat, Bortezomib) |
|---|---|
| FatigueGeneral disorders | 15/16 |
| NauseaGastrointestinal disorders | 14/16 |
| Platelet count decreasedInvestigations | 13/16 |
| Hemoglobin decreasedBlood and lymphatic system disorders | 12/16 |
| DiarrheaGastrointestinal disorders | 12/16 |
| VomitingGastrointestinal disorders | 11/16 |
| Leukocyte count decreasedInvestigations | 9/16 |
| AnorexiaMetabolism and nutrition disorders | 9/16 |
| Aspartate aminotransferase increasedInvestigations | 5/16 |
| Peripheral sensory neuropathyNervous system disorders | 5/16 |
| Age, Continuous(years) | Treatment (Vorinostat, Bortezomib) |
|---|---|
| Median | 62 (34 to 81) |
| Sex: Female, Male(Participants) | Treatment (Vorinostat, Bortezomib) |
|---|---|
| Female | 11 |
| Male | 5 |
| Region of Enrollment(participants) | Treatment (Vorinostat, Bortezomib) |
|---|---|
| United States | 16 |
This study is completed, as verified in Sep 2013. You cannot join it, but the record below documents what was studied.
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National Cancer Institute (NCI)