Trial of the Combination of Bortezomib and Clofarabine in Adults With Relapsed Solid Tumors

  • STATUS
    Recruiting
  • End date
    Jun 2, 2023
  • participants needed
    75
  • sponsor
    National Cancer Institute (NCI)
Updated on 20 June 2022
cancer
lymphoma
clofarabine
neutrophil count
chemotherapy regimen
advanced cancer
primary cancer
neuropathy
bortezomib
solid tumour
bisphosphonate
solid neoplasm

Summary

Background
  • 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.
    Objectives
  • To test the safety and efficacy of the drug combination of bortezomib and clofarabine.
    Eligibility
  • Adults age 18 and over with advanced cancer that has progressed after receiving standard treatment or that has no effective therapy.
    Design
  • 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.

Description

BACKGROUND

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

OBJECTIVES

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 circulating tumor cells before and after treatment

To characterize the changes in MDS residual disease burden that occur with bortezomib and clofarabine treatment

To examine genomic alterations in circulating tumor DNA (ctDNA) that may be associated with response or resistance to clofarabine-bortezomib combination treatment.

ELIGIBILITY
  • 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

STUDY DESIGN:

  • 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.

Details
Condition Neoplasms, Myelodysplastic Syndromes, Lymphomas
Treatment Bortezomib plus Clofarabine
Clinical Study IdentifierNCT02211755
SponsorNational Cancer Institute (NCI)
Last Modified on20 June 2022

Eligibility

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
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Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

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If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

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Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

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