Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02211755
Recruitment Status : Recruiting
First Posted : August 7, 2014
Last Update Posted : April 9, 2020
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Brief 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.

    • 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.

Condition or disease Intervention/treatment Phase
Neoplasms Myelodysplastic Syndromes Lymphomas Drug: Bortezomib plus Clofarabine Phase 1

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)
  • 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

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 75 participants
Allocation: N/A
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
Actual Study Start Date : October 6, 2014
Estimated Primary Completion Date : February 1, 2021
Estimated Study Completion Date : June 2, 2021


Arm Intervention/treatment
Experimental: 1
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




Primary Outcome Measures :
  1. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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: greater than or equal to 1,500/mcL for solid tumors and lymphomas only
  • Platelets: greater than or equal to 100,000/mcL for solid tumors and lymphomas only
  • Total bilirubin: less than or equal to 1.5 X institutional ULN
  • AST(SGOT)/ALT(SGPT): less than or equal to 3 X institutional upper limit of normal

OR

less than 5 X institutional upper limit of normal for

-creatinine: ess 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 on study may be eligible for palliative radiotherapy to non-targeted lesions after 2 cycles of therapy at the PI s discretion). Patients must have recovered to eligibility levels from prior toxicity or adverse events. Treatment with bisphosphonates is permitted.

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.


Information from the National Library of Medicine

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


Contacts
Layout table for location contacts
Contact: Murielle Hogu (240) 858-3335 murielle.hogu@nih.gov
Contact: Naoko Takebe, M.D. (240) 541-4515 takeben@mail.nih.gov

Locations
Layout table for location information
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      
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Naoko Takebe, M.D. National Cancer Institute (NCI)
Additional Information:
Publications:
Layout table for additonal information
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02211755    
Other Study ID Numbers: 140161
14-C-0161
First Posted: August 7, 2014    Key Record Dates
Last Update Posted: April 9, 2020
Last Verified: April 6, 2020

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
Purine Nucleoside Inhibitor
Proteasome Inhibitor
Combination Treatment
Solid Tumors
Hematologic
Additional relevant MeSH terms:
Layout table for MeSH terms
Lymphoma
Preleukemia
Myelodysplastic Syndromes
Syndrome
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Disease
Pathologic Processes
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Bortezomib
Clofarabine
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action