A phase I, open-label, multi-center study to evaluate the pharmacokinetics and safety of oral panobinostat in patients with advanced solid tumors and varying degrees of renal functio

Completed

• Conditions: pharmacokinetic of panobinostat in solid tumors with varying degrees of renal function; 10027655

• Registration Number: NL-OMON36258
• Lead Sponsor: ovartis

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 6 May 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 10

Inclusion Criteria

1. Patient is * 18 years of age
2. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of * 2
3. Patient has documented diagnosis of advanced solid tumor for which no standard systemic therapy exists
4. Patient has the following laboratory values within 2 weeks of starting study drug (labs may be repeated, if needed, to obtain acceptable values before failure at screening is concluded)
a. Creatinine clearance according to a 24-hour urine CrCL (specific criteria for allocation of patients by renal function):
* * 80mL/min for the normal renal function patients
* *50 - <80 mL/min for the mildly renal impaired patients
* *30 - <50 mL/min for the moderately impaired patients
* < 30mL/min for severely renal impaired patients, if applicable
b. Urinalysis: protein (proteinuria) * +2 by dipstick method, or < 100 mg/dL by quantitative method and blood (hematuria) * +1 by dipstick method for normal renal function group patients
c. Hemoglobin * 9 g/dL
d. Absolute neutrophil count (ANC) * 1.5 x 109 /L
e. Platelet count * 100 x 109 /L
f. AST/SGOT and ALT/SGPT * 2.5 x ULN (or * 5 x ULN if transaminase elevation is due to disease involvement)
g. Serum total bilirubin * 1.5 ULN
h. Patient with normal renal function should have serum potassium, magnesium, phosphorus, total calcium (corrected for serum albumin) or ionized calcium within normal limits
5. Patient is able to swallow capsules
6. Patient, if sexually active (men and women of child bearing potential WOCBP), is agreeing to use double barrier method of contraception during the course of the study and for 3 months after completing study treatment. WOCBP are defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months
7. Patient has signed a written informed consent prior to any screening procedures

Exclusion Criteria

1. Patient has received prior treatment with DAC inhibitors including panobinostat
2. Patient is needing valproic acid for any medical condition including during the study or within 5 days prior to the first dose of panobinostat
3. Patient is taking any anti-cancer therapy concomitantly
4. Patient is requiring diuretics unless patient is taking potassium sparring diuretics
5. Patient has active CNS disease or brain metastasis, except those previously treated and stable for at least 3 months
6. Patient has evidence of another malignancy not in remission or history of such a malignancy within the last 3 years (except for treated basal or squamous cell carcinoma, or in situ cancer of the cervix)
7. Patient has received:
a. prior chemotherapy * 3 weeks prior to start of treatment. Patient must have recovered from all therapy-related toxicities
b. biologic immunotherapy including monoclonal antibodies or experimental therapy * 4 weeks prior to start of study
c. radiation therapy * 4 weeks or limited field radiotherapy * 2 weeks prior to start of treatment
8.Patient has not recovered from all therapy-related toxicities to * grade 1 CTCAE or baseline
9. Patient has undergone major surgery * 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy to * grade 1 CTCAE or baseline
10. Patient has unresolved diarrhea * CTCAE grade 2
11. Patient has impaired cardiac function, including any one of the following:
a. LVEF < the lower limit of institutional norm, as determined by ECHO or MUGA
b. obligate use of a permanent cardiac pacemaker
c.congenital long QT syndrome
d. history or presence of ventricular tachyarrhythmias
e. resting bradycardia defined as < 50 beats per minute
f. QTcF > 450 msec on screening ECG
g. Complete left bundle branch block (LBBB), bifasicular block (RBBB with either left
anterior hemiblock or left posterior hemiblock)
h. Any clinically significant ST segment and/or T-wave abnormalities
i. Presence of unstable atrial fibrillation (ventricular response rate > 100 bpm). Patients
with stable atrial fibrillation are allowed in the study provided they do not meet the
other exclusion criteria
j. Myocardial infarction or unstable angina pectoris * 6 months prior to starting study
drug
k. Congestive heart failure (New York Heart Association class III-IV)
l. Other clinically significant heart disease and vascular disease (e.g. uncontrolled
hypertension)
12. Patient is taking medications with relative risk of prolonging the QT interval or inducing
torsade de pointes, if such treatment cannot be discontinued or switched to a different
medication prior to starting study drug
13. Patient has acute renal failure (e.g., acute nephritis, nephritic syndrome, acute tubular
necrosis, glomerolunephritis, pyelonephritis, active hydronephrosis), history of renal
transplant, end stage renal disease (ESRD). However, ESRD is acceptable, if Group 4
(severe) patients are enrolled.
14. Patient is requiring dialysis
15. Patient has impairment of gastrointestinal (GI) function or GI disease that may
significantly alter the absorption of panobinostat (e.g. ulcerative disease, uncontrolled
nausea, vomiting, diarrhea, mal-absorption syndrome, obstruction, or major stomach
and/or small bowel resection)
16. Patient has any other concurrent severe and

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>To assess the effect of varying degrees of renal function (as defined by<br /><br>creatinine clearance) on the pharmacokinetics of panobinostat.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>* To assess the effect of varying degrees of renal function on the safety of<br /><br>panobinostat.<br /><br>* To evaluate whether there is a relationship between PK and safety parameters<br /><br>in patients with varying degrees of renal function<br /><br><br /><br>Exploratory objective:<br /><br>* To explore anti-tumor activity associated with panobinostat (extension phase)</p><br>