Clinical Trials /

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

NCT02211755

Description:

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. - Bortezomib will be injected under the skin on days 1 and 4. - 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.

Related Conditions:
  • Lymphoma
  • Malignant Solid Tumor
  • Myelodysplastic Syndromes
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Trial of the Combination of Bortezomib and Clofarabine in Adults With Relapsed Solid Tumors
  • Official Title: Phase I Trial of the Combination of Bortezomib and Clofarabine in Adults With Refractory Solid Tumors, Lymphomas, or Myelodysplastic Syndromes

Clinical Trial IDs

  • ORG STUDY ID: 140161
  • SECONDARY ID: 14-C-0161
  • NCT ID: NCT02211755

Conditions

  • Neoplasms
  • Myelodysplastic Syndromes

Interventions

DrugSynonymsArms
Bortezomib plus Clofarabine1

Purpose

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 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.

Detailed 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)

      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.
    

Trial Arms

NameTypeDescriptionInterventions
1ExperimentalStarting 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.
  • Bortezomib plus Clofarabine

Eligibility Criteria

        -  INCLUSION CRITERIA

        Patients must have:

        3.1.1 Histologically confirmed solid tumors that have progressed on standard therapy known
        to prolong survival or for which no standard treatment options exist, or

        3.1.1.2 histologically confirmed myelodysplastic syndrome that has progressed on standard
        therapy or for which no standard treatment options exist.

        3.1.2 Age greater than or equal to18 years.

        3.1.3 ECOG performance status less than or equal to 2.

        3.1.4 Life expectancy of greater than 3 months

        3.1.5 Patients must have normal organ and marrow function as defined below:

          -  Absolute neutrophil count <TAB>greater than or equal to 1,500/mcL for solid tumors
             and lymphomas only

          -  Platelets <TAB><TAB><TAB>greater than or equal to 100,000/mcL for solid tumors and
             lymphomas only

          -  Total bilirubin <TAB><TAB>less than or equal to 1.5 X institutional ULN

          -  AST(SGOT)/ALT(SGPT) <TAB>less than or equal to 3 X institutional upper limit of
             normal

        creatinine <TAB><TAB><TAB>less than or equal to 1.5 X institutional ULN

        OR

        creatinine clearance greater than or equal to 60 mL/min/1.73 m2 for patients with
        creatinine levels

        >1.5 mg/dL

        3.1.6 Bortezomib and clofarabine have both been assigned to pregnancy category D by the
        FDA. For this reason, women of child-bearing potential and men must agree to use adequate
        contraception (hormonal or barrier method of birth control; abstinence) prior to study
        entry and for the duration of study participation and for at least 3 months after dosing
        with study drugs ceases. Should a woman become pregnant or suspect she is pregnant while
        she or her partner is participating in this study, she should inform her treating
        physician immediately. Men treated or enrolled on this protocol must also agree to use
        adequate contraception prior to the study, for the duration of study participation, and 3
        months after completion of study drug administration.

        3.1.7 Patients must have completed any chemotherapy, radiation therapy, or biologic
        therapy greater than or equal to 3 weeks (or greather than or equal to 5 half-lives,
        whichever is shorter) prior to entering the study. Patients must be greater than or equal
        to 2 weeks since any prior administration of a study drug in a Phase 0 or equivalent study
        and be greater than or equal to 1 week from palliative radiation therapy. Patients must
        have recovered to eligibility levels from prior toxicity or adverse events. Treatment with
        bisphosphonates is permitted.

        3.1.8 Cardiac function within institutional normal limits on echocardiogram.

        EXCLUSION CRITERIA

        3.2.1 Sensory/motor neuropathy greater than or equal to Grade 2

        3.2.2 QTc interval (Fridericia formula) > 450 msec for men or > 470 msec for women at
        study

        entry; history of congenital long QT syndrome

        3.2.3 Patients who are receiving any other investigational agents.

        3.2.4 Patients with active brain metastases, CNS disease, or carcinomatous meningitis are
        excluded from this clinical trial. Patients with treated brain metastases, whose brain
        metastatic disease has remained stable for greater than or equal to 4 weeks without
        requiring steroid and anti-seizure medication, are eligible to participate.

        3.2.5 History of allergic reactions attributed to compounds of similar chemical or
        biologic composition to study drugs. Patients who have previously received either
        clofarabine or bortezomib will be excluded as this may affect accurate determination of
        the MTD.

        3.2.6 Uncontrolled intercurrent illness including, but not limited to, serious untreated
        infection, symptomatic respiratory failure/congestive heart failure, unstable angina
        pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit
        compliance with study requirements.

        3.2.7 Pregnant women are excluded from this study because bortezomib and clofarabine have
        been assigned to pregnancy category D by the FDA. Because there is an unknown but
        potential risk for adverse events in nursing infants secondary to treatment of the mother
        with the study drugs, breastfeeding should be discontinued prior to the first dose of
        study drug and women should refrain from nursing throughout the treatment period and for 3
        months following the last dose of study drug.

        3.2.8 HIV-positive patients on combination antiretroviral therapy are ineligible because
        of possible pharmacokinetic interactions with study drugs.

        3.2.9 Both men and women of all races and ethnic groups are eligible for this trial.
      
Maximum Eligible Age:110 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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)
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:National Cancer Institute (NCI)

Trial Keywords

  • Purine Nucleoside Inhibitor
  • Proteasome Inhibitor
  • Combination Treatment
  • Solid Tumors

Last Updated

April 20, 2017