Trial of the Combination of Bortezomib and Clofarabine in Adults With Relapsed Solid Tumors
- Researchers want to develop better ways to treat cancer. In this study, they will give people with cancer two drugs. These drugs have been used on their own to treat some blood cell cancers.
- To test the safety and efficacy of the drug combination of bortezomib and clofarabine.
- Adults age 18 and over with advanced cancer that has progressed after receiving standard treatment or that has no effective therapy.
- Participants will be screened with medical history, physical exam, and scans to measure their tumors. They will also have heart, blood, and urine tests. All of these may be done by their regular doctors.
- Participants will get the study drugs in 21-day cyles. They will stay at the clinic for week 1 of every cycle, then have 2 weeks off.
<TAB>- Bortezomib will be injected under the skin on days 1 and 4.
<TAB>- Clofarabine will be injected in a vein for days 1 5.
- During cycle 1 only, participants will go to the clinic or their doctor to have a physical exam and blood tests at the start of the second and third week.
- Participants will have a clinical evaluation throughout the study, before the start of each cycle, before receiving treatment.
- Participants may stay in the study as long as they are tolerating the drugs and their tumor is not getting worse.
- Participants will have follow-up for 30 days after the last dose of study drugs.
|Neoplasms Myelodysplastic Syndromes||Drug: Bortezomib plus Clofarabine||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Phase I Trial of the Combination of Bortezomib and Clofarabine in Adults With Refractory Solid Tumors, Lymphomas, or Myelodysplastic Syndromes|
- To establish the safety, tolerability, and MTD of bortezomib and clofarabine in patients with refractory solid tumors and MDS [ Time Frame: Cycle 1 (21 days) ]
|Study Start Date:||July 30, 2014|
|Estimated Study Completion Date:||August 31, 2018|
|Estimated Primary Completion Date:||February 25, 2018 (Final data collection date for primary outcome measure)|
Starting doses are clofarabine at 1 mg/m(2) IV on days 1 through 5 of a 21-day cycle, and bortezomib at 0.8 mg/m2 subcutaneously on days 1 and 4 of a 21-day cycle.
Drug: Bortezomib plus Clofarabine
The proteasome inhibitor bortezomib and purine nucleoside metabolic inhibitor clofarabine demonstrated greater than additive activity in combination in preclinical xenograft models
The proteasome inhibitor bortezomib and purine nucleoside metabolic inhibitor clofarabine demonstrated greater than additive activity in combination in preclinical xenograft models, justifying the clinical evaluation of this combination for its antitumor activity
To establish the safety, tolerability, and maximum tolerated dose (MTD) of bortezomib and clofarabine in patients with refractory solid tumors, lymphomas, or myelodysplastic syndromes (MDS)
- Study participants must have histologically confirmed solid tumors or lymphomas or myelodysplastic syndromes that have progressed on standard therapy known to prolong survival or for which no standard treatment options exist
- Age greater than or equal to 18
- No major surgery, radiation, or chemotherapy within 3 weeks prior to entering the study
- Adequate organ function
- This is an open-label Phase I trial
- The starting dose of clofarabine will be 1 mg/m2 administered intravenously on days 1 through 5 of a 21-day cycle; bortezomib will be administered at 0.8 mg/m2 subcutaneously on days 1 and 4 of a 21-day cycle.
- Dose escalation will follow a 3+3 design, with dose limiting toxicities defined during cycle 1.
- Dose escalation will proceed in cohorts comprised of two separate groups of patients (one group of patients with solid tumor/lymphoma and one group of patients with MDS), with at least 1 from each group, until hematologic DLT or the second grade 2 hematologic toxicity is observed, at which point, dose escalation will proceed separately for two cohorts: (1) patients with solid tumors/lymphoma and (2) patients with MDS.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02211755
|Contact: Jennifer H Zlott||(301) firstname.lastname@example.org|
|Contact: Alice P Chen, M.D.||(301) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office 888-624-1937|
|Principal Investigator:||Alice P Chen, M.D.||National Cancer Institute (NCI)|