Cardiovascular Safety Study of Tipifarnib in Patients With Advanced Solid Malignancies

A Phase I, Open-label Clinical Pharmacology Study to Evaluate the Effect of Tipifarnib on Cardiac Safety in Subjects With Advanced Solid Malignancies

A Phase I, open-label clinical pharmacology study designed to evaluate the effect of tipifarnib on cardiac repolarization (corrected QT interval [QTc] duration) following a single dose of 900 mg and after repeated twice daily administration of 600 mg in subjects with advanced solid malignancies. Subjects will receive a 900 mg single dose at cycle 1 day 1 follow by 600 mg twice a day orally with a meal (Days 2-7 and 15-21) in 28-day cycles. Beginning on Day 2 of Cycle 1, subjects will self-administer 600 mg tipifarnib, orally with a meal, bid for 7 days in alternating weeks (Days 2-7 and 15-21) in 28-day cycles. The secondary objectives are to evaluate the safety and PK of tipifarnib. Series of PK will be collected on day -1 of Cycle 1, Cycle 1 day 1 and Cycle 1 day 7.

Study Overview

• Status: Terminated
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Drug: Tipifarnib

Detailed Description

Phase I study will evaluate the effect of tipifarnib on cardiac repolarization (corrected QT interval [QTc] duration) following a single dose of 900 mg and after repeated twice daily administration of 600 mg in subjects with advanced solid malignancies. The study will enroll approximately 20 subjects with advanced solid malignancies (at least 8, but no more than 12, male subjects). Subjects must have no approved/appropriate therapeutic options available. Subject will undergo series of ECG at Cycle 1 day -1 follow by study drug dosing, series of Pharmacokinetic and ECG at Cycle 1 day 1 and Cycle 1 day 7. Beginning on Day 2 of Cycle 1, subjects will self-administer 600 mg tipifarnib, orally with a meal, bid for 7 days in alternating weeks (Days 2-7 and 15-21) in 28-day cycles. For Cycle 2 and beyond, subjects will self-administer 600 mg bid on Days 1-7 and Days 15-21 in 28-day cycles.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Canton, Ohio, United States, 44718
      • Gabrail Cancer Center Research
  • Texas
    • Austin, Texas, United States, 78758
      • Next Oncology
    • San Antonio, Texas, United States, 78229
      • Next Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. At least 18 years of age.
2. Advanced solid tumor malignancies for whom no other therapy or intervention is available
3. Confirmation of measurable disease by RECIST v1.1
4. No uncontrolled hypertension, defined as >140/90 mm Hg
5. A normal 12-lead ECG
6. At least two weeks since the last systemic anticancer therapy regimen prior to Cycle 1 Day 1; this includes radiation therapy.
7. ECOG performance status of 0-2.
8. Acceptable liver, renal and hematological function
9. Other protocol defined inclusion criteria may apply.

Exclusion Criteria

1. Has disease that is suitable for therapy administered with curative intent.
2. Ongoing treatment with another anticancer agent indicated for the malignancy for which the subject is enrolling into the study (excluding adjuvant hormonal therapy for breast cancer and hormonal treatment for castration sensitive prostate cancer).
3. History of cardiomyopathy, unstable angina within prior 6 months, myocardial infarction within prior 6 months, cerebrovascular attack within prior 6 months, history of New York Heart Association grade III or greater congestive heart failure, or current serious cardiac arrhythmia requiring medication.
4. Non-tolerable Grade 2 or ≥ Grade 3 neuropathy or evidence of unstable neurological symptoms within 4 weeks of Cycle 1 Day 1.
5. Major surgery, other than diagnostic surgery, within 14 days prior to Cycle 1 Day 1, without complete recovery.
6. Active, uncontrolled bacterial, viral or fungal infections requiring systemic therapy.
7. Other protocol defined exclusion may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Single Group Assignment; Single Arm - Drug administered on Days 1-7 and Days 15-21 of a 28-day treatment cycle. Series of Pharmacokinetics and ECGs will be done during cycle 1.	Drug: Tipifarnib; Cardiac Safety of Tipifarnib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change from baseline in time-matched difference in QTc interval to post-baseline time points after a single 900 mg dose and multiple 600 mg BID doses of tipifarnib in subjects with Advanced Solid Malignancies	The analysis will be performed using the concentration-QTc modeling approach (Garnett 2018) and the by-time point modeling approach defined in the International Council on Harmonisation (ICH) E14 guidance. The analysis will be performed using triplicate, time-matched ECG measurements of the QTc interval will be taken at baseline, Day 1 (900 mg tipifarnib) and Day 7 (600 mg tipifarnib BID) at predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post dose (24 hour on day 1 only).	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Investigate safety and tolerability of tipifarnib according to NCI CTCAE v5.0	Incidence of adverse events, incidence of abnormal laboratory test results, abnormal vital signs, and abnormal ECG results	30 days after treatment discontinuation

Collaborators and Investigators

• Sponsor: Kura Oncology, Inc.
• Investigators: Principal Investigator: David Sommerhalder, MD, Next Oncology

Study record dates

Study Major Dates

• Study Start (Actual): May 6, 2021
• Primary Completion (Actual): May 2, 2023
• Study Completion (Actual): May 2, 2023

Study Registration Dates

• First Submitted: March 4, 2021
• First Submitted That Met QC Criteria: April 26, 2021
• First Posted (Actual): April 29, 2021

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 19, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents; Tipifarnib
• Other Study ID Numbers: KO-TIP-011

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No