Trial of the Combination of Bortezomib and Clofarabine in Adults With Relapsed Solid Tumors
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|ClinicalTrials.gov Identifier: NCT02211755|
Recruitment Status : Recruiting
First Posted : August 7, 2014
Last Update Posted : July 26, 2021
- 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 clinical evaluations throughout the study, including before receiving treatment and then before the start of each cycle.
- 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.
- The first part of this study tests the safety of different doses of clofarabine and bortezomib.
- The second part of this study involves a separate group of participants who will undergo mandatory research biopsies to learn more about the effects of clofarabine and bortezomib on cancer cells.
|Condition or disease||Intervention/treatment||Phase|
|Neoplasms Myelodysplastic Syndromes Lymphomas||Drug: Bortezomib plus Clofarabine||Phase 1|
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)
- To determine the molecular effects of the clofarabine-bortezomib combination on biomarkers of cell death and DNA damage in tumor biopsy tissue
- To explore the mechanism of action of the bortezomib and clofarabine combination by
examining markers of DNA damage and apoptosis in tumor cells before and after treatment
-To characterize the changes in MDS residual disease burden that occur with bortezomib
and clofarabine treatment
- 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.
- Up to 33 patients will be accrued to a PD expansi n cohort at the MTD to further assess pharmacodynamic endpoints in tumor and blood.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||75 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Trial of the Combination of Bortezomib and Clofarabine in Adults With Refractory Solid Tumors, Lymphomas, or Myelodysplastic Syndromes|
|Actual Study Start Date :||October 6, 2014|
|Estimated Primary Completion Date :||June 2, 2023|
|Estimated Study Completion Date :||June 2, 2023|
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
- Safety and MTD [ Time Frame: Cycle 1 (21 days) ]To establish the safety, tolerability, and maximum tolerated dose (MTD) of bortezomib and clofarabine in patients with refractory solid tumors or lymphomas or myelodysplastic syndromes
- Biomarkers of DNA damage and apoptosis in circulating tumor cells [ Time Frame: Baseline, cycle 1 day 1, and cycle 2 day 1 ]To determine the effects of the clofarabine-bortezomib combination on biomarkers of DNA damage and apoptosis in circulating tumor cells
- Biomarkers of cell death and DNA damage in tumor biopsy tissue [ Time Frame: Baseline, cycle 1 day 1, and cycle 2 day 4/day 5 ]To determine the effects of the clofarabine-bortezomib combination on biomarkers of cell death and DNA damage in tumor biopsy tissue
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02211755
|Contact: Murielle Hogu||(240) firstname.lastname@example.org|
|Contact: Naoko Takebe, M.D.||(240) 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:||Naoko Takebe, M.D.||National Cancer Institute (NCI)|