Advanced Solid TumorPhase 1NCT04887194
PK Study to Assess Drug-drug Interaction and QTc Between Sitravatinib and a Cocktail of Substrates
A Phase 1 study testing Sitravatinib, Warfarin and Dextromethorphan in people with Advanced Solid Tumor, run by Mirati Therapeutics Inc. at 5 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumor
- What is being tested?
- Sitravatinib, Warfarin and Dextromethorphan
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 5 sitesUnited States
- Study dates
- 8 Apr 2021to 22 Dec 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Confirmed diagnosis of unresectable advanced/metastatic solid tumor
- Life expectancy of at least 3 months
- Adequate bone marrow and organ function
Who cannot join
- 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
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
NEXT Oncology
Austin, Texas, 78758
NEXT Oncology
Fairfax, Virginia, 22031
Goshen Health
Goshen, Indiana, 46526
NEXT Oncology
San Antonio, Texas, 78229
MultiCare Health System
Tacoma, Washington, 98402
About this study
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
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.
Read the 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.
- Conditions
- Advanced Solid Tumor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SitravatinibDrug
Also called MGCD516
Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases
WarfarinDrug
Also called Coumadin
CYP2C9 probe substrate
DextromethorphanDrug
Also called Robitussin
CYP2D6 probe substrate
MidazolamDrug
Also called Versed
CYP3A4 probe substrate
DigoxinDrug
Also called LANOXICAPS
P-gp probe substrate
RosuvastatinDrug
Also called Crestor
BCRP probe substrate
NivolumabDrug
Also called OPDIVO
Nivolumab is a programmed death receptor (PD-1) blocking antibody
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Drug: Sitravatinib; Drug: Warfarin; Drug: Dextromethorphan; Drug: Midazolam; Drug: Digoxin; Drug: Rosuvastatin |
| 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. Receives: Drug: Sitravatinib |
| 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. Receives: Drug: Sitravatinib; Drug: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
PK parameters of probe drugs; AUC from time zero to the last data point (AUC-last)
(warfarin, dextromethorphan, midazolam, digoxin, and rosuvastatin) derived from the plasma concentration time profile before and after oral administration of sitravatinib
Measured: Part 1; 1-20 Days
PK parameters of probe drugs; AUC from time zero to infinity (AUC∞)
(warfarin, dextromethorphan, midazolam, digoxin, and rosuvastatin) derived from the plasma concentration time profile before and after oral administration of sitravatinib
Measured: Part 1; 1-20 Days
PK parameters of probe drugs; C-max
(warfarin, dextromethorphan, midazolam, digoxin, and rosuvastatin) derived from the plasma concentration time profile before and after oral administration of sitravatinib
Measured: Part 1; 1-20 Days
Adverse Events
Characterization of AEs by incidence, severity, timing, seriousness \& relationship to study treatment
Measured: Through study completion, an average of 12 months
Secondary outcomes (6)
Plasma PK parameters of sitravatinib and M10; C-max
C-max
Measured: 1-20 Days
Plasma PK parameters of sitravatinib and M10; AUC over the dosing interval (AUC)
AUC over the dosing interval (AUC)
Measured: 1-20 Days
Plasma PK parameters of sitravatinib and M10; trough plasma concentration (C-trough)
trough plasma concentration (C-trough)
Measured: 1-20 Days
Plasma PK parameters of sitravatinib and M10; time to maximum concentration (t-max)
time to maximum concentration (t-max)
Measured: 1-20 Days
Adverse Events
Safety characterized by type, incidence, severity, timing, seriousness \& relationship to study treatment of adverse events, and laboratory abnormalities
Measured: 1-20 Days
QT/QTc
ECG data
Measured: Part 1: Pre-dose to Day 10 (QTc cohort); Part 1: Pre-dose to Day14 (DDI cohort)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 May 2021
- Study start8 Apr 2021
- Primary completion22 Dec 2022
- Study completion22 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Solid TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Two Part, Phase 1 study enrolling patients with advanced tumor types into two cohorts: drug-drug interaction (DDI) and QTc. All patients receive the same anticancer treatment.
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mirati Therapeutics Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Curtis Chin, MD, Study director, Mirati Therapeutics Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04887194
- Sponsor's protocol ID
- 516-010
- Status last verified
- May 2024
- First submitted
- 4 May 2021
- Last updated
- 8 May 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04887194
- Acronym / sponsor ID
- 516-010
- Conditions
- Advanced Solid Tumor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Mirati Therapeutics Inc.Industry (pharma, biotech, devices)
- Study start
- 8 Apr 2021 (actual)
- Primary completion
- 22 Dec 2022 (actual)
- Study completion
- 22 Dec 2022 (actual)
- First posted
- 14 May 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Two Part, Phase 1 study enrolling patients with advanced tumor types into two cohorts: drug-drug interaction (DDI) and QTc. All patients receive the same anticancer treatment.
| Arm | Type | Receives |
|---|---|---|
| Phase 1, Part 1: Sitravatinib monotherapy (DDI cohort) | Experimental | Drug: Sitravatinib, Drug: Warfarin, Drug: Dextromethorphan, Drug: Midazolam, Drug: Digoxin, Drug: RosuvastatinTo 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 | Drug: SitravatinibTo 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 | Drug: Sitravatinib, Drug: NivolumabTo evaluate safety and tolerability of Sitravatinib treatment with the addition of the checkpoint inhibitor nivolumab. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Confirmed diagnosis of unresectable advanced/metastatic solid tumor
- Life expectancy of at least 3 months
- Adequate bone marrow and organ function
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SitravatinibAlso: MGCD516Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases | Drug | Phase 1, Part 1: Sitravatinib monotherapy (DDI cohort), Phase 1, Part 1: Sitravatinib monotherapy (QTc cohort), Phase 1, Part 2: Combination Therapy (both DDI and QTc cohorts) |
| WarfarinAlso: CoumadinCYP2C9 probe substrate | Drug | Phase 1, Part 1: Sitravatinib monotherapy (DDI cohort) |
| DextromethorphanAlso: RobitussinCYP2D6 probe substrate | Drug | Phase 1, Part 1: Sitravatinib monotherapy (DDI cohort) |
| MidazolamAlso: VersedCYP3A4 probe substrate | Drug | Phase 1, Part 1: Sitravatinib monotherapy (DDI cohort) |
| DigoxinAlso: LANOXICAPSP-gp probe substrate | Drug | Phase 1, Part 1: Sitravatinib monotherapy (DDI cohort) |
| RosuvastatinAlso: CrestorBCRP probe substrate | Drug | Phase 1, Part 1: Sitravatinib monotherapy (DDI cohort) |
| NivolumabAlso: OPDIVONivolumab is a programmed death receptor (PD-1) blocking antibody | Drug | Phase 1, Part 2: Combination Therapy (both DDI and QTc cohorts) |
Primary outcome
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
6 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)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2024.
Related trials for Advanced Solid Tumor
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 1
A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
Neoplasms
RecruitingPhase 1/2
A Study of Neladalkib (NVL-655) in Patients With Advanced NSCLC and Other Solid Tumors Harboring ALK Rearrangement or Activating ALK Mutation (ALKOVE-1)
Locally Advanced Solid Tumor, Metastatic Solid Tumor
Active, not recruitingPhase 2
Testing AZD5363 as a Potential Targeted Treatment in Cancers With AKT Genetic Changes (MATCH-Subprotocol Y)
Advanced Lymphoma, Advanced Malignant Solid Neoplasm
RecruitingPhase 1/2
Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer
Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Curtis Chin, MD study director
Mirati Therapeutics Inc.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Sitravatinib, Warfarin and Dextromethorphan in people with Advanced Solid Tumor, run by Mirati Therapeutics Inc. at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PK parameters of probe drugs; AUC from time zero to the last data point (AUC-last) (time frame: Part 1; 1-20 Days). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2024.