Clinical trial NCT05828303: A Phase 1 Study to Evaluate the Potential Drug Interactions Between Repotrectinib and Metformin, Digoxin, and Rosuvastatin in Patients With Advanced Solid Tumors
Official title: A Phase 1, Open-Label, Fixed-Sequence Study to Evaluate the Potential Drug Interactions Between Repotrectinib and Metformin, Digoxin, and Rosuvastatin in Patients With Advanced Solid Tumors Harboring ROS1 or NTRK1-3 Rearrangements
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Advanced Solid Tumor
Metastatic Solid Tumor
Lead sponsor: Turning Point Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2023-04-25
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a Phase 1 study to evaluate the potential drug-drug interaction (DDI) effect of repotrectinib on certain drug transporters in patients with advanced cancer.

Detailed description: This is a Phase 1, open-label, fixed-sequence study to evaluate the potential drug-drug interaction (DDI) effect of repotrectinib on drug transporters (metformin, digoxin and rosuvastatin) following multiple dose administration of repotrectinib in patients with advanced cancer harboring ROS1 and NTRK1 Rearrangements.

Eligibility criteria: Key Inclusion Criteria:

1. Histologically or cytologically confirmed diagnosis of locally advanced, or metastatic solid tumor (including primary central nervous system \[CNS\] tumors) that harbors a ROS1 or NTRK1-3 gene fusion.
2. Patient must have a documented ROS1 or NTRK1-3 gene fusion determined by tissue-based local testing.
3. Patients must have an Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 (≥ 18 years).
4. Protocol specified baseline hematology, liver function and kidney function laboratory values.

Key Exclusion Criteria:

1. Concurrent participation in another therapeutic clinical trial.
2. Symptomatic brain metastases or leptomeningeal involvement.
3. Major surgery within 4 weeks of start of repotrectinib treatment.
4. Clinically significant cardiovascular disease.
5. History of non-pharmacologically induced prolonged QTc interval
6. Known active infections requiring ongoing treatment (bacterial, fungal, viral including human immunodeficiency virus positivity).
7. Gastrointestinal disease or other malabsorption syndromes.
8. Current or anticipated use of drugs that are known to be moderate or strong CYP3A inhibitors or inducers.
9. Patients who have received, or are expected to receive metformin, digoxin or rosuvastatin within 14 days prior to beginning of the DDI assessment period.
10. Patients who have received or are expected to receive drugs that are inhibitors of P-gp, OATP1B1, BCRP, and MATE2-K within 14 days or 5 half-lives (whichever is longer) prior to beginning of the DDI assessment period until the DDI assessment period is completed.

Primary outcomes:
measure: Area under plasma-concentration time curve
timeFrame: Within 28 days of first cocktail dose
measure: Maximum Observed Plasma Concentration
timeFrame: Within 28 days of first cocktail dose
Secondary outcomes:
measure: Evaluate safety and tolerability
timeFrame: Within 28 days of first cocktail dose
Other outcomes:
Locations:
city: Canton
country: United States
facility: Gabrail Cancer Research Center
state: Ohio
city: Canton
country: United States
facility: Local Institution - 2101
state: Ohio
city: Westmead
country: Australia
facility: Local Institution - 2119
state: New South Wales
city: Botafogo
country: Brazil
facility: Local Institution - 2126
state: RJ
city: Porto Alegre
country: Brazil
facility: Local Institution - 2132
state: RS
city: Porto Alegre
country: Brazil
facility: Local Institution - 2134
state: RS
city: Sao Paulo
country: Brazil
facility: Local Institution - 2130
state: SP
city: Sao Paulo
country: Brazil
facility: Local Institution - 2108
city: Bordeaux
country: France
facility: Local Institution - 2123
city: La Tronche
country: France
facility: Local Institution - 2122
city: Marseille
country: France
facility: Local Institution - 2117
city: Nantes
country: France
facility: Local Institution - 2115
city: Poitiers
country: France
facility: Local Institution - 2121
city: Rennes
country: France
facility: Local Institution - 2136
city: Saint-Herblain
country: France
facility: Local Institution - 2120
city: Milan
country: Italy
facility: Local Institution - 2135
state: MI
city: Rozzano
country: Italy
facility: Local Institution - 2116
state: MI
city: Perugia
country: Italy
facility: Local Institution - 2111
state: PG
city: Aviano
country: Italy
facility: Local Institution - 2104
state: PN
city: Verona
country: Italy
facility: Local Institution - 2103
state: VR
city: Naples
country: Italy
facility: Local Institution - 2114
city: Barcelona
country: Spain
facility: Local Institution - 2124
state: B
city: Barcelona
country: Spain
facility: Local Institution - 2113
state: B
city: Barcelona
country: Spain
facility: Local Institution - 2105
state: B
city: Pozuelo de Alarcon
country: Spain
facility: Local Institution - 2129
state: Madrid
city: Madrid
country: Spain
facility: Local Institution - 2138
state: M
city: Madrid
country: Spain
facility: Local Institution - 2110
state: M
city: Madrid
country: Spain
facility: Local Institution - 2128
state: M
city: Barcelona
country: Spain
facility: Local Institution - 2109
city: Madrid
country: Spain
facility: Local Institution - 2127
city: Madrid
country: Spain
facility: Local Institution - 2106
city: Pamplona
country: Spain
facility: Local Institution - 2112
city: Valencia
country: Spain
facility: Local Institution - 2125
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: