---
title: PK Study to Assess Drug-drug Interaction and QTc Between Sitravatinib and a Cocktail of Substrates
nct_id: NCT04887194
overall_status: COMPLETED
phase: PHASE1
sponsor: Mirati Therapeutics Inc.
study_type: INTERVENTIONAL
primary_condition: Advanced Solid Tumor
countries: United States
canonical_url: "https://parkinsonspathways.com/agent/trials/NCT04887194.md"
clinicaltrials_gov: "https://clinicaltrials.gov/study/NCT04887194"
ct_last_update_post_date: 2024-05-08
last_seen_at: "2026-05-12T07:07:23.614Z"
source: ClinicalTrials.gov (mirrored, no enrichment)
---
# PK Study to Assess Drug-drug Interaction and QTc Between Sitravatinib and a Cocktail of Substrates

**Official Title:** A Two-cohort, Two-part, Phase 1, Multicenter, Open-label, Fixed-sequence, Drug-Drug Interaction and QTc Assessments of Sitravatinib Followed by Combination Treatment With Nivolumab in Patients With Advanced Solid Malignancies

**NCT ID:** [NCT04887194](https://clinicaltrials.gov/study/NCT04887194)

## Key Facts

- **Status:** COMPLETED
- **Phase:** PHASE1
- **Study Type:** INTERVENTIONAL
- **Target Enrollment:** 40
- **Lead Sponsor:** Mirati Therapeutics Inc.
- **Conditions:** Advanced Solid Tumor
- **Start Date:** 2021-04-08
- **Completion Date:** 2022-12-22
- **CT.gov Last Update:** 2024-05-08

## Brief Summary

Study 516-010 is an open-label Phase 1, drug-drug interaction and QTc study evaluating the effect of sitravatinib on probe substrates for CYP450 enzymes and BCRP and P-gp transporters.

## Detailed Description

Part 1 of this study is designed to evaluate the potential for drug-drug interactions and QTc effects with sitravatinib monotherapy when administered with probe drugs for specific cytochrome P450 (CYP) enzymes (CYP2C9, CYP2D6, and CYP3A4) and P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) transporters

Part 2 allows for patients to continue sitravatinib treatment with the addition of the checkpoint inhibitor Nivolumab.

## Eligibility

- **Minimum age:** 18 Years
- **Sex:** ALL
- **Healthy Volunteers:** No

```
Inclusion Criteria:

* Confirmed diagnosis of unresectable advanced/metastatic solid tumor
* Life expectancy of at least 3 months
* Adequate bone marrow and organ function

Exclusion Criteria:

* Ongoing medical condition or need for treatment with medication that may affect the PK of study treatments during Part 1
* Immunocompromising conditions
* Impaired heart function
* Active or prior documented autoimmune disease
```

## Arms

- **Phase 1, Part 1: Sitravatinib monotherapy (DDI cohort)** (EXPERIMENTAL) — To evaluate the potential for drug-drug interactions (DDI) with sitravatinib monotherapy. To determine the effect of sitravatinib on the pharmacokinetics (PK) of midazolam (CYP3A4 probe substrate), warfarin (CYP2C9 probe substrate), dextromethorphan (CYP2D6 probe substrate), rosuvastatin (BCRP probe substrate), and digoxin (P-gp probe substrate).
- **Phase 1, Part 1: Sitravatinib monotherapy (QTc cohort)** (EXPERIMENTAL) — To evaluate the QTc prolongation risk for sitravatinib in patients with advanced/metastatic solid tumors via C-QTc modeling.
- **Phase 1, Part 2: Combination Therapy (both DDI and QTc cohorts)** (EXPERIMENTAL) — To evaluate safety and tolerability of Sitravatinib treatment with the addition of the checkpoint inhibitor nivolumab.

## Interventions

- **Sitravatinib** (DRUG) — Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases
- **Warfarin** (DRUG) — CYP2C9 probe substrate
- **Dextromethorphan** (DRUG) — CYP2D6 probe substrate
- **Midazolam** (DRUG) — CYP3A4 probe substrate
- **Digoxin** (DRUG) — P-gp probe substrate
- **Rosuvastatin** (DRUG) — BCRP probe substrate
- **Nivolumab** (DRUG) — Nivolumab is a programmed death receptor (PD-1) blocking antibody

## Primary Outcomes

- **PK parameters of probe drugs; AUC from time zero to the last data point (AUC-last)** _(time frame: Part 1; 1-20 Days)_ — (warfarin, dextromethorphan, midazolam, digoxin, and rosuvastatin) derived from the plasma concentration time profile before and after oral administration of sitravatinib
- **PK parameters of probe drugs; AUC from time zero to infinity (AUC∞)** _(time frame: Part 1; 1-20 Days)_ — (warfarin, dextromethorphan, midazolam, digoxin, and rosuvastatin) derived from the plasma concentration time profile before and after oral administration of sitravatinib
- **PK parameters of probe drugs; C-max** _(time frame: Part 1; 1-20 Days)_ — (warfarin, dextromethorphan, midazolam, digoxin, and rosuvastatin) derived from the plasma concentration time profile before and after oral administration of sitravatinib
- **Adverse Events** _(time frame: Through study completion, an average of 12 months)_ — Characterization of AEs by incidence, severity, timing, seriousness \& relationship to study treatment

## Secondary Outcomes

- **Plasma PK parameters of sitravatinib and M10; C-max** _(time frame: 1-20 Days)_
- **Plasma PK parameters of sitravatinib and M10; AUC over the dosing interval (AUC)** _(time frame: 1-20 Days)_
- **Plasma PK parameters of sitravatinib and M10; trough plasma concentration (C-trough)** _(time frame: 1-20 Days)_
- **Plasma PK parameters of sitravatinib and M10; time to maximum concentration (t-max)** _(time frame: 1-20 Days)_
- **Adverse Events** _(time frame: 1-20 Days)_
- **QT/QTc** _(time frame: Part 1: Pre-dose to Day 10 (QTc cohort); Part 1: Pre-dose to Day14 (DDI cohort))_

## Locations (5)

- Goshen Health, Goshen, Indiana, United States
- NEXT Oncology, Austin, Texas, United States
- NEXT Oncology, San Antonio, Texas, United States
- NEXT Oncology, Fairfax, Virginia, United States
- MultiCare Health System, Tacoma, Washington, United States

## Recent Field Changes (last 30 days)

- `status.overallStatus` — added _(2026-05-12)_
- `status.primaryCompletionDate` — added _(2026-05-12)_
- `status.completionDate` — added _(2026-05-12)_
- `status.lastUpdatePostDate` — added _(2026-05-12)_
- `design.phases` — added _(2026-05-12)_
- `design.enrollmentCount` — added _(2026-05-12)_
- `eligibility.criteria` — added _(2026-05-12)_
- `eligibility.minAge` — added _(2026-05-12)_
- `eligibility.sex` — added _(2026-05-12)_
- `outcomes.primary` — added _(2026-05-12)_
- `outcomes.secondary` — added _(2026-05-12)_
- `armsInterventions.arms` — added _(2026-05-12)_
- `armsInterventions.interventions` — added _(2026-05-12)_
- `sponsor.lead` — added _(2026-05-12)_
- `results.hasResults` — added _(2026-05-12)_
- `locations.goshen health|goshen|indiana|united states` — added _(2026-05-12)_
- `locations.next oncology|austin|texas|united states` — added _(2026-05-12)_
- `locations.next oncology|san antonio|texas|united states` — added _(2026-05-12)_
- `locations.next oncology|fairfax|virginia|united states` — added _(2026-05-12)_
- `locations.multicare health system|tacoma|washington|united states` — added _(2026-05-12)_

---

*Canonical: https://parkinsonspathways.com/agent/trials/NCT04887194.md*  
*Source data (authoritative): https://clinicaltrials.gov/study/NCT04887194*  
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