Bortezomib and Clofarabine in Treating Patients with Refractory Solid Tumors

Status: Approved


This phase I trial studies the safety and best dose of bortezomib and clofarabine in treating patients with solid tumors that did not respond to treatment. Bortezomib and clofarabine may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Eligibility Criteria

Inclusion Criteria

  • Patients must have histologically confirmed solid tumors that have progressed on standard therapy known to prolong survival or for which no standard treatment options exist
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Life expectancy of greater than 3 months
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Total bilirubin =<1.5 x institutional upper limit of normal (IULN)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional upper limit of normal
  • Creatinine =< 1.5 x institutional ULN OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels > 1.5 mg/dL
  • 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
  • Patients must have completed any chemotherapy, radiation therapy, or biologic therapy >= 3 weeks prior to entering the study; patients must be >= 2 weeks since any prior administration of a study drug in a phase 0 or equivalent study; patients must have recovered to eligibility levels from prior toxicity or adverse events; treatment with bisphosphonates is permitted
  • Cardiac function within institutional normal limits on echocardiogram

Exclusion Criteria

  • Sensory/motor neuropathy >= grade 2
  • Corrected QT (QTc) interval (Fridericia formula) > 450 msec for men or > 470 msec for women at study entry; history of congenital long QT syndrome
  • Patients who are receiving any other investigational agents
  • Patients with active brain metastases or carcinomatous meningitis are excluded from this clinical trial; patients with treated brain metastases, whose brain metastatic disease has remained stable for >= 4 weeks without requiring steroid and anti-seizure medication, are eligible to participate
  • 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
  • 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
  • Pregnant women are excluded; 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
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
  • Both men and women of all races and ethnic groups are eligible for this trial

Locations & Contacts


National Cancer Institute Developmental Therapeutics Clinic
Status: Active
Contact: Shivaani Kummar
Phone: 800-411-1222
National Institutes of Health Clinical Center
Status: Active
Contact: A P Chen
Phone: 301-496-4291

Trial Objectives and Outline


I. To establish the safety, tolerability, and maximum tolerated dose (MTD) of the combination of bortezomib and clofarabine in patients with refractory solid tumors.

OUTLINE: This is a dose-escalation study of bortezomib and clofarabine.

Patients receive bortezomib subcutaneously (SC) on days 1 and 4 and clofarabine intravenously (IV) over 1 hour on days 1-5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days.

Trial Phase & Type

Trial Phase

Phase I

Trial Type


Lead Organization

Lead Organization
NCI - Center for Cancer Research

Principal Investigator
A P Chen

Trial IDs

Primary ID 14-C-0161
Secondary IDs 9762, NCI-2014-00816, NCI-2014-01108, 344856, 140161, 141572 ID NCT02211755