Advanced or Metastatic Solid TumorsEarly Phase 1TITANNCT03454243
Oral Immunomodulatory Tyrosine Kinase Inhibitor in Patients With Locally Advanced or Metastatic Solid Tumors
A Early Phase 1 study testing RXDX-106 in people with Advanced or Metastatic Solid Tumors, run by Hoffmann-La Roche at 1 site in United States.
Trial summary
This is a first-in-human, open label, multicenter, dose escalation study of RXDX-106 in patients with locally advanced or metastatic solid tumors, who have no available therapy likely to convey clinical benefit. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced or Metastatic Solid Tumors
- What is being tested?
- RXDX-106
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Feb 2018to 5 Jun 2018
- Phase
- Early 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
- Patients with histologically or cytologically confirmed diagnosis of locally advanced or metastatic solid tumor disease for which standard therapy is not effective, available, acceptable, or is intolerable.
- Dose level 2 (20 mg) and higher: willing to provide baseline and on treatment tumor biopsies (3 weeks after RXDX-106 treatment initiation), provided the procedure is clinically feasible and not deemed unsafe by the investigator.
- Prior anticancer therapy is allowed, including prior checkpoint inhibitor treatment.
- Must have measurable disease per RECIST 1.1 as assessed by computed tomography (CT) scan or magnetic resonance imaging (MRI).
- Lesion/s deemed accessible to biopsy for both before and on-treatment biopsies.
- Males or females aged ≥18 years at screening.
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- Screening laboratory values:
- Hemoglobin ≥9 g/dL
- Absolute neutrophil count ≥1500 cells/mm3
- Platelet count ≥100,000 cells/mm3
- Total bilirubin ≤1.5 × upper limit of normal (ULN)
- Aspartate aminotransferase and alanine aminotransferase ≤2.5 × ULN
- Serum creatinine ≤1.5 mg/dL or estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2
- International Normalized Ratio (INR) or prothrombin time (PT) ≤1.5 × ULN (unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants)
- Activated partial thromboplastin time (aPTT) ≤1.5 × ULN (unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants)
- TSH within normal limits at baseline, (if not WLN, then total T3 or free T3 and free T4 should be within normal limits) or stable with treatment.
- Patients with treated stable CNS metastases that are asymptomatic (including leptomeningeal carcinomatosis) are allowed, if there is no evidence of progression for at least 4 weeks after CNS-directed treatment as ascertained by clinical examination and brain imaging. Patients requiring steroids must be at a stable or decreasing dose (≤10 mg/day dexamethasone or equivalent) for at least 2 weeks prior to the start of treatment. The use of seizure prophylaxis is allowed.
- Resolution of any clinically significant toxic effects of prior therapy to grade 0 or 1 according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.03 (exception of alopecia and grade 2 peripheral neuropathy).
- Eastern Cooperative Oncology Group (ECOG) performance status of <2.
- Other inclusion criteria apply.
Who cannot join
- Treated with systemic anticancer therapy or an investigational agent within 2 weeks or 5 half-lives, whichever is shorter, prior to start of study drug treatment. Washout will be 2 weeks for antibody therapy and immunotherapy.
- Major surgery 21 days or less prior to starting study drug or has not recovered from adverse effects from such procedure.
- Radiotherapy within 2 weeks prior to start of study drug treatment (palliative radiation or stereotactic radiosurgery within 7 days prior to start of study treatment). Patients must have recovered from all radiotherapy-related toxicities.
- Has received a live-virus vaccination within 30 days prior to start of study drug treatment.
- Seasonal flu and other inactivated vaccines that do not contain live virus are permitted.
- Severe or unstable medical condition, such as congestive heart failure (New York Heart Association [NYHA] Class III or IV), ischemic heart disease, uncontrolled hypertension, uncontrolled diabetes mellitus, psychiatric condition, as well as an uncontrolled cardiac arrhythmia requiring medication (≥grade 2, according to NCI CTCAE v4.03), myocardial infarction within 6 months prior to starting study treatment, or any other significant or unstable concurrent medical illness that in the opinion of the investigator would preclude protocol therapy.
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- History of non-pharmacologically induced prolonged QTc interval >480 milliseconds.
- History of other previous or concurrent cancer that would interfere with the determination of safety or efficacy assessment of RXDX-106 with respect to the qualifying solid tumor malignancy.
- Major active infection requiring parenteral antibiotics.
- Known HIV infection or active infection with hepatitis B or C. Patients with unknown status at the time of enrollment must be tested during screening.
- Unable to swallow oral medication.
- Active gastrointestinal disease (eg, Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would reasonably impact drug absorption.
- Active autoimmune disease requiring immunosuppressive treatment or history of autoimmune disease requiring immunosuppressive therapy (e.g. requirement for systemic therapy with >10 mg/day prednisone-equivalent) or any other concurrent use of immunosuppressive therapy.
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment.
- Active retinal pigment epithelium (RPE)/photoreceptor disorders such as; retinitis pigmentosa, cone-rod dystrophies, Bests dystrophy, Stargardt disease (STGD), macular degeneration.
- Current participation in another clinical study of an investigational agent, vaccine, or device. Concomitant participation in observational studies is acceptable after sponsor approval.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Study of RXDX-106, an Oral Immunomodulatory TYRO3, AXL, and MER (TAM) Tyrosine Kinase Inhibitor, in Patients With Locally Advanced or Metastatic Solid Tumors
This is a first-in-human, open label, multicenter, dose escalation study of RXDX-106 in patients with locally advanced or metastatic solid tumors, who have no available therapy likely to convey clinical benefit.
This study will examine the safety, tolerability, pharmacokinetics (PK), pharmacodynamics and preliminary efficacy of RXDX 106.
Read the detailed description
The primary objective of Phase 1 is to assess safety and tolerability, determine the recommended phase 2 dose (RP2D) and assess the pharmacokinetics of RXDX-106. The secondary objective is to evaluate the preliminary antitumor activity of RXDX-106, as assessed by objective response rate (ORR) using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and Immune Response Related Criteria in Solid Tumors (iRECIST) in patients with advanced or metastatic solid tumors.
The proposed starting dose of RXDX-106 was calculated based upon nonclinical toxicology studies to determine a recommended first-in-human starting dose, which may be below the biologically active level. Therefore, in order to minimize the number of patients treated at this dose, an accelerated titration design will be used for the first cohort, after which, a conventional 3+3 scheme will be followed for enrollment in subsequent dose levels.
Final determination of the single agent RP2D will be based on available safety, tolerability, PK, pharmacodynamics, and efficacy data from different dose levels and schedules tested, but will be no higher than the maximum tolerated dose. After RP2D has been determined, additional expansion cohorts of patients (up to 15) with specific tumor types, treatment history, and/or expression of a specific biomarker may be enrolled.
- Conditions
- Advanced or Metastatic Solid Tumors
- Being tested
- RXDX-106
- Keywords
- Solid Tumors, TYRO3, AXL, MER, Receptor tyrosine kinases (RTKs), Checkpoint inhibitors, Melanoma, Non-small cell lung cancer (NSCLC), Squamous cell carcinoma, Hodgkin lymphoma, Urothelial carcinoma, Microsatellite instability-high carcinomas, TAM Inhibitor
- Medical subject headings
- Melanoma, Carcinoma, Non-Small-Cell Lung, Carcinoma, Squamous Cell, Hodgkin Disease, Carcinoma, Transitional Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RXDX-106Drug
Patients will receive continuous daily oral doses of RXDX-106 in 21 day cycles. To determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D), study drug will be administered in an escalated fashion starting at dose of 10 mg/day and will proceed at the dose levels prespecified by the dose escalation schema. Once daily dosing for RXDX-106 will initially be tested. However, other dosing schedules (eg, every other day, weight based, etc) may be tested based on safety and PK data to optimize drug exposure.
| Study group | Role | What they receive |
|---|---|---|
| RXDX-106 | Experimental | Not described Receives: Drug: RXDX-106 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose Limint Toxicities (DLT)
Determine dose-limiting toxicities of RXDX-106
Measured: 21 days following first dose of RXDX-106
Maximum Tolerated Dose (MTD)
Determine MTD of RXDX-106
Measured: 21 days following first dose of RXDX-106
Recommended Phase 2 Dose (RP2D)
Determine RP2D of RXDX-106
Measured: Approximately 12 months
Secondary outcomes (7)
Objective Response Rate (ORR)
Radiographic measurement per RECIST v1.1 and iRECIST as assessed by Investigator
Measured: Approximately 2 years
Duration of Response
Per RECIST v1.1 and iRECIST as assessed by Investigator
Measured: Approximately 2 years
Overall Survival (OS)
Measured: Approximately 2 years
Progression-Free Survival (PFS)
Measured: Approximately 2 years
Maximum observed plasma concentration (Cmax)
Measured: Approximately 2 years
Time of maximum observed plasma concentration (Tmax)
Measured: Approximately 2 years
AUC throughout dosing interval (AUCτ)
Measured: Approximately 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2018
- Study start15 Feb 2018
- Primary completion5 Jun 2018
- Study completion5 Jun 2018
Why it stopped: Sponsor's decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced or Metastatic Solid TumorsStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Dose escalation, conventional 3+3 scheme
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pratik S. Multani, MD, MS, Study chair, Chief Medical Officer, Ignyta, Inc.Sandra Pierina D'Angelo, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03454243
- Sponsor's protocol ID
- RXDX-106-01
- Acronym
- TITAN
- Status last verified
- Apr 2019
- First submitted
- 21 Feb 2018
- Last updated
- 25 Apr 2019
- 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 25 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study of RXDX-106, an Oral Immunomodulatory TYRO3, AXL, and MER (TAM) Tyrosine Kinase Inhibitor, in Patients With Locally Advanced or Metastatic Solid Tumors
- ClinicalTrials.gov ID
- NCT03454243
- Acronym / sponsor ID
- TITAN / RXDX-106-01
- Conditions
- Advanced or Metastatic Solid Tumors
- Keywords
- Solid Tumors, TYRO3, AXL, MER, Receptor tyrosine kinases (RTKs), Checkpoint inhibitors, Melanoma, Non-small cell lung cancer (NSCLC)
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor's decision
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 15 Feb 2018 (actual)
- Primary completion
- 5 Jun 2018 (actual)
- Study completion
- 5 Jun 2018 (actual)
- First posted
- 5 Mar 2018 (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.
This is a first-in-human, open label, multicenter, dose escalation study of RXDX-106 in patients with locally advanced or metastatic solid tumors, who have no available therapy likely to convey clinical benefit.
This study will examine the safety, tolerability, pharmacokinetics (PK), pharmacodynamics and preliminary efficacy of RXDX 106.
Detailed description
The primary objective of Phase 1 is to assess safety and tolerability, determine the recommended phase 2 dose (RP2D) and assess the pharmacokinetics of RXDX-106. The secondary objective is to evaluate the preliminary antitumor activity of RXDX-106, as assessed by objective response rate (ORR) using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and Immune Response Related Criteria in Solid Tumors (iRECIST) in patients with advanced or metastatic solid tumors.
The proposed starting dose of RXDX-106 was calculated based upon nonclinical toxicology studies to determine a recommended first-in-human starting dose, which may be below the biologically active level. Therefore, in order to minimize the number of patients treated at this dose, an accelerated titration design will be used for the first cohort, after which, a conventional 3+3 scheme will be followed for enrollment in subsequent dose levels.
Final determination of the single agent RP2D will be based on available safety, tolerability, PK, pharmacodynamics, and efficacy data from different dose levels and schedules tested, but will be no higher than the maximum tolerated dose. After RP2D has been determined, additional expansion cohorts of patients (up to 15) with specific tumor types, treatment history, and/or expression of a specific biomarker may be enrolled.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Dose escalation, conventional 3+3 scheme
| Arm | Type | Receives |
|---|---|---|
| RXDX-106 | Experimental | Drug: RXDX-106 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Patients with histologically or cytologically confirmed diagnosis of locally advanced or metastatic solid tumor disease for which standard therapy is not effective, available, acceptable, or is intolerable.
- Dose level 2 (20 mg) and higher: willing to provide baseline and on treatment tumor biopsies (3 weeks after RXDX-106 treatment initiation), provided the procedure is clinically feasible and not deemed unsafe by the investigator.
- Prior anticancer therapy is allowed, including prior checkpoint inhibitor treatment.
- Must have measurable disease per RECIST 1.1 as assessed by computed tomography (CT) scan or magnetic resonance imaging (MRI).
- Males or females aged ≥18 years at screening.
Key exclusion criteria (16 listed)
- Treated with systemic anticancer therapy or an investigational agent within 2 weeks or 5 half-lives, whichever is shorter, prior to start of study drug treatment. Washout will be 2 weeks for antibody therapy and immunotherapy.
- Major surgery 21 days or less prior to starting study drug or has not recovered from adverse effects from such procedure.
- Radiotherapy within 2 weeks prior to start of study drug treatment (palliative radiation or stereotactic radiosurgery within 7 days prior to start of study treatment). Patients must have recovered from all radiotherapy-related toxicities.
- Has received a live-virus vaccination within 30 days prior to start of study drug treatment.
- Severe or unstable medical condition, such as congestive heart failure (New York Heart Association [NYHA] Class III or IV), ischemic heart disease, uncontrolled hypertension, uncontrolled diabetes mellitus, psychiatric condition, as well as an uncontrolled cardiac arrhythmia requiring medication (≥grade 2, according to NCI CTCAE v4.03), myocardial infarction within 6 months prior to starting study treatment, or any other significant or unstable concurrent medical illness that in the opinion of the investigator would preclude protocol therapy.
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 |
|---|---|---|
| RXDX-106Patients will receive continuous daily oral doses of RXDX-106 in 21 day cycles. To determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D), study drug will be administered in an escalated fashion starting at dose of 10 mg/day and will proceed at the dose levels prespecified by the dose escalation schema. Once daily dosing for RXDX-106 will initially be tested. However, other dosing schedules (eg, every other day, weight based, etc) may be tested based on safety and PK data to optimize drug exposure. | Drug | RXDX-106 |
Primary outcome
Dose Limint Toxicities (DLT)
Time frame: 21 days following first dose of RXDX-106
Determine dose-limiting toxicities of RXDX-106
Maximum Tolerated Dose (MTD)
Time frame: 21 days following first dose of RXDX-106
Determine MTD of RXDX-106
Recommended Phase 2 Dose (RP2D)
Time frame: Approximately 12 months
Determine RP2D of RXDX-106
7 secondary outcomes
Objective Response Rate (ORR)
Time frame: Approximately 2 years
Duration of Response
Time frame: Approximately 2 years
Overall Survival (OS)
Time frame: Approximately 2 years
Progression-Free Survival (PFS)
Time frame: Approximately 2 years
Maximum observed plasma concentration (Cmax)
Time frame: Approximately 2 years
Time of maximum observed plasma concentration (Tmax)
Time frame: Approximately 2 years
AUC throughout dosing interval (AUCτ)
Time frame: Approximately 2 years
Results and safety
The study was stopped early (reason given: Sponsor's decision). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Apr 2019.
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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.
Pratik S. Multani, MD, MS study chair
Chief Medical Officer, Ignyta, Inc.
Sandra Pierina D'Angelo, MD principal investigator
Memorial Sloan Kettering Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing RXDX-106 in people with Advanced or Metastatic Solid Tumors, run by Hoffmann-La Roche at 1 site 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 20 inclusion and 16 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: stopped early, as of the sponsor's last update on 25 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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 was stopped early (reason given: Sponsor's decision). Results are not available in the source record.
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?
Dose Limint Toxicities (DLT) (time frame: 21 days following first dose of RXDX-106). The study lists 3 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 25 Apr 2019.