Tocilizumab with or without Zidovudine and Valganciclovir in Treating Patients with Kaposi Sarcoma Herpes Virus-Associated Multicentric Castleman Disease
Basic Trial Information
|Phase II||Biomarker/Laboratory analysis, Treatment||Active||18 and over||11-C-0233|
NCI-2013-01504, 110233, P10788, NCT01441063
This pilot phase II trial studies tocilizumab in treating patients with Kaposi sarcoma herpes virus-associated multicentric Castleman disease. Monoclonal antibodies, such as tocilizumab, can block the ability of cancer to grow and spread. Herpes virus is found in the lesions of most patients with Kaposi's sarcoma and may help cause Kaposi's sarcoma. Zidovudine and valganciclovir are antiviral drugs that act against many types of herpes viruses. Giving tocilizumab with zidovudine and valganciclovir may be an effective treatment for Kaposi's sarcoma herpes virus-associated multicentric Castleman disease.
Further Study Information
I. Estimate clinical benefit of tocilizumab 8 mg/kg every 2 weeks for up to 12 weeks in patients with symptomatic Kaposi sarcoma herpes virus-associated multicentric Castleman disease (KSHV-MCD) using a modified KSHV-MCD Clinical Benefit Response Criteria.
I. Evaluate best clinical, biochemical, radiographic, and overall response in patients with KSHV-associated MCD treated for up to 12 weeks with tocilizumab 8 mg/kg every 2 weeks using the prior National Cancer Institute (NCI) KSHV-MCD Response Criteria.
II. In patients with inadequate response to tocilizumab monotherapy: explore preliminarily the activity of tocilizumab 8 mg/kg every 2 weeks, combined with zidovudine (AZT) 600 mg orally every (q) 6 hours (every 6 hours) and valganciclovir (VGC) 900 mg orally q 12 hours (every 12 hours) on days 1-5 of a 14-day cycle.
III. Evaluate safety and tolerability of tocilizumab alone and in combination with AZT/VGC in this patient population.
IV. Evaluate the effect of tocilizumab on the pharmacokinetics of antiretroviral agents that are cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) substrates in patients with symptomatic KSHV-MCD.
V. Evaluate of effect of therapy on Kaposi sarcoma (KS) using modified acquired immune deficiency syndrome (AIDS) Clinical Trials Group (ACTG) response criteria.
VI. Evaluate progression-free and overall survival with tocilizumab and tocilizumab/AZT/VGC.
TOCILIZUMAB ADMINISTRATION: Patients receive tocilizumab intravenously (IV) over 60 minutes on day 1. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
HIGH-DOSE AZT AND VGC ADMINISTRATION: Patients with progressive disease or patients not achieving response by course 4 also receive zidovudine* orally (PO) four times daily (QID) and valganciclovir* PO twice daily (BID) on days 1-5.
*NOTE: Patients not tolerating oral therapy may receive zidovudine IV over 60 minutes QID and valganciclovir IV over 60 minutes BID.
After completion of study treatment, patients are followed up for 4 months.
Pathologically confirmed KSHV-MCD
At least one clinical symptom probably or definitely attributed to KSHV-MCD
Intermittent or persistent fever for at least 1 week (> 38°C)
Fatigue (Common Terminology Criteria for Adverse Events [CTCAE] grade 2 or greater)
Gastrointestinal symptoms (includes nausea and anorexia) (CTCAE grade 1 or greater)
Respiratory symptoms (includes cough and airway hyperreactivity) (CTCAE grade 1 or greater)
At least one laboratory abnormality probably or definitely attributed to KSHV-MCD
Anemia (hemoglobin [Hgb] [men] =< 12.5 gm/dL, Hgb [women] =< 11 gm/dL)
Thrombocytopenia (=< 130,000/mm^3)
Hypoalbuminemia (< 3.4 g/dL)
Elevated C-reactive protein (CRP) (CRP > 3 mg/L)] probably or definitely attributable to KSHV-MCD
No life- or organ-threatening manifestations of MCD
Eastern Cooperative Oncology Group (ECOG) performance status =< 2
Human immunodeficiency virus (HIV)-infected patients should be receiving or willing to initiate an effective combination antiretroviral therapy (cART) regimen
Willingness to complete tuberculosis evaluation and start prophylactic antituberculosis therapy as soon as is medically feasible if patients have a reactive tuberculin skin test and/or positive QuantiFERON-tuberculosis (TB) Gold test and have not completed an adequate course of prevented anti-tuberculosis therapy, following American Thoracic Society/Centers for Disease Control recommended guidelines
Ability to understand and willingness to give informed consent
Women of child bearing potential must agree to use birth control for the duration of the study
Uncontrolled bacterial, mycobacterial, or fungal infection
Uncontrolled intercurrent illness including, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements or ability to receive therapy
Pregnant or lactating women
Any abnormality that would be scored as NCI Common Toxicity Criteria (CTC) grade 3 toxicity that is unrelated to HIV, its treatment, or to MCD that would preclude protocol treatment; exceptions include:
Direct manifestations of Kaposi sarcoma or MCD
Direct manifestation of HIV (i.e. low cluster of differentiation [CD]4 count)
Direct manifestation of HIV therapy (i.e. hyperbilirubinemia associated with protease inhibitors)
Elevated creatinine kinase (CK) attributed to exercise
Past or present history of malignant tumors other than Kaposi sarcoma unless one of the following:
Complete remission for >= 1 year from completion of therapy
Completely resected basal cell carcinoma
In situ squamous cell carcinoma of the cervix or anus
Patients with concurrent Kaposi sarcoma requiring immediate cytotoxic chemotherapy
History of tocilizumab therapy within prior 6 weeks
History of rituximab or intravenous bevacizumab therapy within six weeks
History of >= 2 allergic reaction or any grade anaphylactic reaction during prior administration of tocilizumab
Trial Contact Information
Trial Lead Organizations / Sponsors / Collaborators
NCI - Center for Cancer Research
- National Cancer Institute
National Institutes of Health Clinical Center
Thomas S. Uldrick
Thomas S. Uldrick
Link to the current ClinicalTrials.gov record.
NLM Identifier NCT01441063
Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.