Cardiovascular Safety Study of Tipifarnib in Patients With Advanced Solid Malignancies

NCT04865159 | Terminated Phase 1 FDA Drug

• 1 other identifier: KO-TIP-011
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Advanced Solid Tumor

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Investigate safety and tolerability of tipifarnib according to NCI CTCAE v5.0

  30 days after treatment discontinuation

Study Arms (1)

Single Group Assignment

OTHER

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

Interventions

Tipifarnib DRUG

Cardiac Safety of Tipifarnib

Single Group Assignment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Has disease that is suitable for therapy administered with curative intent.
• 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).
• 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.
• Non-tolerable Grade 2 or ≥ Grade 3 neuropathy or evidence of unstable neurological symptoms within 4 weeks of Cycle 1 Day 1.
• Major surgery, other than diagnostic surgery, within 14 days prior to Cycle 1 Day 1, without complete recovery.
• Active, uncontrolled bacterial, viral or fungal infections requiring systemic therapy.

Sponsors & Collaborators

• Kura Oncology, Inc.: lead

Study Sites (3)

Gabrail Cancer Center Research

Canton, Ohio, 44718, United States

Location

NEXT Oncology

Austin, Texas, 78758, United States

Location

NEXT Oncology

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Interventions

tipifarnib

Study Officials

• David Sommerhalder, MD

  NEXT Oncology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Model Details: Tipifarnib will be administered with a meal at a starting single dose of 900 mg, orally, once on Day 1, Cycle 1 followed by 600 mg, orally bid on Cycle 1 Days 2-7 and Days 15-21 for a 28-day treatment cycle.

Study Record Dates

• First Submitted: March 4, 2021
• First Posted: April 29, 2021
• Study Start: May 6, 2021
• Primary Completion: May 2, 2023
• Study Completion: May 2, 2023
• Last Updated: September 21, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)