Solid TumorsPhase 1NCT01877811
Study of RXDX-105, Potent RET Inhibitor in Patients With Advanced Lung Cancer and Other Solid Tumors
A Phase 1 study testing RXDX-105 in people with Solid Tumors, run by Hoffmann-La Roche at 14 sites in United States.
Trial summary
This is a first-in-human, multicenter, open-label study consisting of 2 phases. Phase 1 is a dose escalation study of RXDX-105 (formerly known as CEP-32496) in patients with advanced solid tumors aimed at defining the recommended Phase 2 dose (RP2D) and schedule for administration. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumors
- What is being tested?
- RXDX-105
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 143 participants
- Where
- 14 sitesUnited States
- Study dates
- Jun 2013to Feb 2019
- 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
- Patients must have histologically or cytologically confirmed advanced solid tumors with a histology and/or molecular alteration of interest as defined in Section 4, detected by a CLIA-certified or equivalently accredited diagnostic laboratory
- Squamous NSCLC and Non-squamous NSCLC (no known RET alterations or BRAF V600E mutations) patients must have archival tissue available for analysis by Ignyta; all other patients must send tissue to Ignyta, if tissue is available
- Prior Treatment:
- Patients with BRAF V600E mutations must be TKI-naïve; any number of other prior therapies are allowed
- NSCLC patients with RET alterations who have had a prior RET inhibitor or are RET inhibitor-naïve will be enrolled; (any number of other prior therapies are allowed); all other histologies with RET alterations must be RET inhibitor-naïve
- Patients with Squamous NSCLC and Non-squamous NSCLC (no known RET alterations or BRAF V600E mutations) may have had prior TKIs and any number of other prior therapies
Show all 11Show fewer
- Measurable disease according to RECIST v1.1 for all patients except patients with RET altered tumors; patients with RET altered tumors must have evaluable disease, but are not required to have measurable disease
- Patients with treated, stable CNS metastases, including leptomeningeal carcinomatosis are allowed. The use of seizure prophylaxis is allowed. Patients requiring steroids must be at a stable or decreasing dose for at least 2 weeks prior to the start of RXDX-105 treatment.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- Able to ingest oral medication
- 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 (4 weeks for antibody therapy and immunotherapy, and 2 weeks for bevacizumab in colon cancer patients)
- Major surgery 21 days or less prior to starting study drug or has not recovered from adverse effects of such therapy
- 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
- History of non-pharmacologically induced prolonged QTc interval (e.g., repeated demonstration of a QTc interval > 500 milliseconds from ECGs performed at least 24 hours apart)
- Major active infection requiring parenteral antibiotics
- 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 other previous cancer that would interfere with the determination of safety or efficacy of RXDX-105 with respect to the qualifying solid tumor malignancy
- Known infection with human immunodeficiency virus (HIV) and active hepatitis B or hepatitis C
- Current participation in another clinical study of an investigational agent, vaccine, or device. Concomitant participation in observational studies is acceptable
- Presence of a significant gastrointestinal disorder that, in the opinion of the Investigator or Sponsor, could interfere with absorption of RXDX-105 (e.g., malabsorption syndrome, gastrointestinal surgery)
- Known hypersensitivity to any of the components of RXDX-105
Trial locations and contacts
14 sites in 1 country.
14 sites in 1 country
United States14 sites
University Cancer & Blood Center, LLC
Athens, Georgia
Massachusetts General Hospital/Beth Israel Deaconess Med. Ctr./Dana Farber Cancer Institute
Boston, Massachusetts
Henry Ford Health System
Detroit, Michigan
Karmanos Cancer Center
Detroit, Michigan
City of Hope
Duarte, California
University of Texas MD Anderson Cancer Center
Houston, Texas
University of California Irvine College of Medicine
Irvine, California
Memorial Sloan Kettering Cancer Center
New York, New York
Fox Chase Cancer Center
Philadelphia, Pennsylvania
University of California San Diego Moores Cancer Center
San Diego, California
Florida Cancer Center
Sarasota, Florida
University of Washington, Seattle Cancer Care Alliance
Seattle, Washington
Washington University
St Louis, Missouri
Lombardi Comprehensive Cancer Center, Georgetown
Washington D.C., District of Columbia
About this study
Official title: An Open-Label, Phase 1/1b, Single-Agent Study of RXDX-105 in Patients With Advanced Solid Tumors
This is a first-in-human, multicenter, open-label study consisting of 2 phases. Phase 1 is a dose escalation study of RXDX-105 (formerly known as CEP-32496) in patients with advanced solid tumors aimed at defining the recommended Phase 2 dose (RP2D) and schedule for administration. Phase 1b is a dose expansion in approximately 90 patients with advanced solid tumors with specific histologies and/or molecular alterations of interest. Patients in Phase 1b will be treated at the RP2D determined in Phase 1.
Read the detailed description
The primary objective of Phase 1 is to determine the recommended Phase 2 dose (RP2D) of RXDX-105. The primary objective of Phase 1b is to further assess the safety profile and tolerability of RXDX-105 at the RP2D The secondary objective is to evaluate the antitumor activity of RXDX-105 at the RP2D, as assessed by objective response rate (ORR) (complete response [CR] or partial response [PR]) using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) in patients with advanced solid tumors with RET or BRAF mutations or rearrangements.
The RP2D has been determined and Phase 1 portion of the study is now closed to new patient enrollment.
Phase 1 b is open and enrolling patients with solid tumors harboring a RET rearrangement or mutation, or a BRAF rearrangement or mutation. Additionally, patients with Squamous NSCLC and lung adenocarcinomas with other alterations than RET or BRAF such as KRAS mutations, etc. will also be enrolled. Approximately 90 patients will be enrolled in Phase 1b.
Each phase of this study will consist of a 28-day screening period. Patients will be treated in 28-day treatment cycles until documented radiographic progression, unacceptable toxicity, withdrawal of consent, or protocol specified parameters to stop treatment. Patients in Phase 1 and 1b will be followed for 6 months after the last dose of study treatment.
- Conditions
- Solid Tumors
- Being tested
- RXDX-105
- Keywords
- Lung Cancer, RET Inhibitor, Solid Tumors, RET mutations or rearrangements, BRAF mutations or rearrangements, Squamous NSCLC, KRAS mutation, Other Lung adenocarcinomas
- Medical subject headings
- Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RXDX-105Drug
Also called CEP-32496, AC013773
During Phase 1/1b, subjects will receive daily oral doses of RXDX-105 in 28-day cycles (except for Day 2 of Cycle 1). To determine the recommended Phase 2 dose (RP2D), doses will be administered in an escalated fashion starting at 20 mg/day.
During Phase 1b, subjects will be administered the RP2D in 28-day treatment cycles until documented radiographic progression, unacceptable toxicity, withdrawal of consent, or protocol specified parameters to stop treatment.
| Study group | Role | What they receive |
|---|---|---|
| RXDX-105 | Experimental | Not described Receives: Drug: RXDX-105 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1: Dose Limiting Toxicities
From signing of the informed consent up to approximately 12 months
Measured: Approximately 12 months
Phase 1: Occurrence of Adverse Events
From signing of the informed consent up to approximately 12 months
Measured: Approximately 12 months
Phase 1b: Occurrence of Adverse Events
To further assess the safety profile and tolerability of RXDX-105 at the RP2D
Measured: Approximately 12 months
Secondary outcomes (11)
Phase 1: Maximum observed plasma drug concentration (Cmax)
Measured: Day 1 to Day 16
Phase 1: Time of maximum observed plasma drug concentration (tmax)
Measured: Day 1 to Day 16
Phase 1: Area under the plasma drug concentration versus time curve from time 0 to infinity (AUC0-∞)
Measured: Day 1 to Day 16
Phase 1: Area under the plasma drug concentration versus time curve from time 0 to the last measureable drug concentration (AUC0-t)
Measured: Day 1 to Day 16
Phase 1: Area under the plasma drug concentration versus time curve from time 0 to 24 hours after study drug administration (AUC0-24)
Measured: Day 1 to Day 16
Phase 1: Terminal elimination rate constant (λz)
Measured: Day 1 to Day 16
Phase 1: Terminal elimination half-life (t1/2)
Measured: Day 1 to Day 16
Phase 1: Apparent clearance of study drug from plasma (CL/F)
Measured: Day 1 to Day 16
Phase 1b: Objective Response Rate
Objective response rate is defined as the proportion of patients with advanced solid tumors achieving best overall response of complete response (CR), or partial response (PR), as assessed using RECIST v1.1
Measured: Approximately 12 months
Phase 1b: Duration of Objective Response
The duration of objective response is defined as the time interval from the date of first documented response (CR or PR) to disease progression or death, whichever occurs first
Measured: Approximately 12 months
Phase 1b: Clinical Benefit Rate
Clinical benefit rate is defined as the proportion of patients achieving a complete response (CR), partial response (PR) or stable disease (SD) for 6 months
Measured: Approximately 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2013 (estimated)
- Study startJun 2013
- Primary completionDec 2018
- Study completionFeb 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for 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
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 143 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01877811
- Sponsor's protocol ID
- RXDX-105-01
- Status last verified
- Apr 2019
- First submitted
- 6 May 2013
- Last updated
- 25 Apr 2019
- Results posted
- No
- Data monitoring committee
- No
Publications
Pietrantonio F, Di Nicolantonio F, Schrock AB, Lee J, Morano F, Fuca G, Nikolinakos P, Drilon A, Hechtman JF, Christiansen J, Gowen K, Frampton GM, Gasparini P, Rossini D, Gigliotti C, Kim ST, Prisciandaro M, Hodgson J, Zaniboni A, Chiu VK, Milione M, Patel R, Miller V, Bardelli A, Novara L, Wang L, Pupa SM, Sozzi G, Ross J, Di Bartolomeo M, Bertotti A, Ali S, Trusolino L, Falcone A, de Braud F, Cremolini C. RET fusions in a small subset of advanced colorectal cancers at risk of being neglected. Ann Oncol. 2018 Jun 1;29(6):1394-1401. doi: 10.1093/annonc/mdy090.
PubMed 29538669
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
- An Open-Label, Phase 1/1b, Single-Agent Study of RXDX-105 in Patients With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT01877811
- Acronym / sponsor ID
- RXDX-105-01
- Conditions
- Solid Tumors
- Keywords
- Lung Cancer, RET Inhibitor, Solid Tumors, RET mutations or rearrangements, BRAF mutations or rearrangements, Squamous NSCLC, KRAS mutation, Other Lung adenocarcinomas
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 143 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- Jun 2013
- Primary completion
- Dec 2018 (actual)
- Study completion
- Feb 2019 (actual)
- First posted
- 14 Jun 2013 (estimated)
- 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, multicenter, open-label study consisting of 2 phases. Phase 1 is a dose escalation study of RXDX-105 (formerly known as CEP-32496) in patients with advanced solid tumors aimed at defining the recommended Phase 2 dose (RP2D) and schedule for administration. Phase 1b is a dose expansion in approximately 90 patients with advanced solid tumors with specific histologies and/or molecular alterations of interest. Patients in Phase 1b will be treated at the RP2D determined in Phase 1.
Detailed description
The primary objective of Phase 1 is to determine the recommended Phase 2 dose (RP2D) of RXDX-105. The primary objective of Phase 1b is to further assess the safety profile and tolerability of RXDX-105 at the RP2D The secondary objective is to evaluate the antitumor activity of RXDX-105 at the RP2D, as assessed by objective response rate (ORR) (complete response [CR] or partial response [PR]) using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) in patients with advanced solid tumors with RET or BRAF mutations or rearrangements.
The RP2D has been determined and Phase 1 portion of the study is now closed to new patient enrollment.
Phase 1 b is open and enrolling patients with solid tumors harboring a RET rearrangement or mutation, or a BRAF rearrangement or mutation. Additionally, patients with Squamous NSCLC and lung adenocarcinomas with other alterations than RET or BRAF such as KRAS mutations, etc. will also be enrolled. Approximately 90 patients will be enrolled in Phase 1b.
Each phase of this study will consist of a 28-day screening period. Patients will be treated in 28-day treatment cycles until documented radiographic progression, unacceptable toxicity, withdrawal of consent, or protocol specified parameters to stop treatment. Patients in Phase 1 and 1b will be followed for 6 months after the last dose of study treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| RXDX-105 | Experimental | Drug: RXDX-105 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Patients must have histologically or cytologically confirmed advanced solid tumors with a histology and/or molecular alteration of interest as defined in Section 4, detected by a CLIA-certified or equivalently accredited diagnostic laboratory
- Prior Treatment:
- Measurable disease according to RECIST v1.1 for all patients except patients with RET altered tumors; patients with RET altered tumors must have evaluable disease, but are not required to have measurable disease
- Patients with treated, stable CNS metastases, including leptomeningeal carcinomatosis are allowed. The use of seizure prophylaxis is allowed. Patients requiring steroids must be at a stable or decreasing dose for at least 2 weeks prior to the start of RXDX-105 treatment.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
Key exclusion criteria (11 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 (4 weeks for antibody therapy and immunotherapy, and 2 weeks for bevacizumab in colon cancer patients)
- Major surgery 21 days or less prior to starting study drug or has not recovered from adverse effects of such therapy
- 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
- History of non-pharmacologically induced prolonged QTc interval (e.g., repeated demonstration of a QTc interval > 500 milliseconds from ECGs performed at least 24 hours apart)
- Major active infection requiring parenteral antibiotics
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-105Also: CEP-32496, AC013773During Phase 1/1b, subjects will receive daily oral doses of RXDX-105 in 28-day cycles (except for Day 2 of Cycle 1). To determine the recommended Phase 2 dose (RP2D), doses will be administered in an escalated fashion starting at 20 mg/day. During Phase 1b, subjects will be administered the RP2D in 28-day treatment cycles until documented radiographic progression, unacceptable toxicity, withdrawal of consent, or protocol specified parameters to stop treatment. | Drug | RXDX-105 |
Primary outcome
Phase 1: Dose Limiting Toxicities
Time frame: Approximately 12 months
From signing of the informed consent up to approximately 12 months
Phase 1: Occurrence of Adverse Events
Time frame: Approximately 12 months
From signing of the informed consent up to approximately 12 months
Phase 1b: Occurrence of Adverse Events
Time frame: Approximately 12 months
To further assess the safety profile and tolerability of RXDX-105 at the RP2D
11 secondary outcomes
Phase 1: Maximum observed plasma drug concentration (Cmax)
Time frame: Day 1 to Day 16
Phase 1: Time of maximum observed plasma drug concentration (tmax)
Time frame: Day 1 to Day 16
Phase 1: Area under the plasma drug concentration versus time curve from time 0 to infinity (AUC0-∞)
Time frame: Day 1 to Day 16
Phase 1: Area under the plasma drug concentration versus time curve from time 0 to the last measureable drug concentration (AUC0-t)
Time frame: Day 1 to Day 16
Phase 1: Area under the plasma drug concentration versus time curve from time 0 to 24 hours after study drug administration (AUC0-24)
Time frame: Day 1 to Day 16
Phase 1: Terminal elimination rate constant (λz)
Time frame: Day 1 to Day 16
Phase 1: Terminal elimination half-life (t1/2)
Time frame: Day 1 to Day 16
Phase 1: Apparent clearance of study drug from plasma (CL/F)
Time frame: Day 1 to Day 16
Phase 1b: Objective Response Rate
Time frame: Approximately 12 months
Phase 1b: Duration of Objective Response
Time frame: Approximately 12 months
Phase 1b: Clinical Benefit Rate
Time frame: Approximately 12 months
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 25 Apr 2019.
- Derived from this study: PubMed 29538669Pietrantonio F, Di Nicolantonio F, Schrock AB, Lee J, Morano F, Fuca G, Nikolinakos P, Drilon A, Hechtman JF, Christiansen J, Gowen K, Frampton GM, Gasparini P, Rossini D, Gigliotti C, Kim ST, Prisciandaro M, Hodgson J, Zaniboni A, Chiu VK, Milione M, Patel R, Miller V, Bardelli A, Novara L, Wang L, Pupa SM, Sozzi G, Ross J, Di Bartolomeo M, Bertotti A, Ali S, Trusolino L, Falcone A, de Braud F, Cremolini C. RET fusions in a small subset of advanced colorectal cancers at risk of being neglected. Ann Oncol. 2018 Jun 1;29(6):1394-1401. doi: 10.1093/annonc/mdy090.
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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.
The record lists no contact. Use the official record to reach the sponsor.
14 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 RXDX-105 in people with Solid Tumors, run by Hoffmann-La Roche at 14 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 11 inclusion and 11 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 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 14 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?
Phase 1: Dose Limiting Toxicities (time frame: Approximately 12 months). 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?
On the ClinicalTrials.gov record for NCT01877811, which also lists 1 linked publication.
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; AzTrials last refreshed its copy on 8 Nov 2026.