Solid Tumors Clinical Trial
Official title:
An Open-Label, Phase 1/1b, Single-Agent Study of RXDX-105 in Patients With Advanced Solid Tumors
NCT number | NCT01877811 |
Other study ID # | RXDX-105-01 |
Secondary ID | |
Status | Completed |
Phase | Phase 1 |
First received | |
Last updated | |
Start date | June 2013 |
Est. completion date | February 2019 |
Verified date | April 2019 |
Source | Hoffmann-La Roche |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 143 |
Est. completion date | February 2019 |
Est. primary completion date | December 2018 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility |
Inclusion Criteria for Phase 1b: 1. 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 2. 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 3. 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 4. 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. 5. Eastern Cooperative Oncology Group (ECOG) performance status = 2 6. Able to ingest oral medication 7. Other inclusion criteria apply Exclusion Criteria for Phase 1b: 1. 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) 2. Major surgery 21 days or less prior to starting study drug or has not recovered from adverse effects of such therapy 3. 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 4. 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) 5. Major active infection requiring parenteral antibiotics 6. 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 7. 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 8. Known infection with human immunodeficiency virus (HIV) and active hepatitis B or hepatitis C 9. Current participation in another clinical study of an investigational agent, vaccine, or device. Concomitant participation in observational studies is acceptable 10. 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) 11. Known hypersensitivity to any of the components of RXDX-105 |
Country | Name | City | State |
---|---|---|---|
United States | University Cancer & Blood Center, LLC | Athens | Georgia |
United States | Massachusetts General Hospital/Beth Israel Deaconess Med. Ctr./Dana Farber Cancer Institute | Boston | Massachusetts |
United States | Henry Ford Health System | Detroit | Michigan |
United States | Karmanos Cancer Center | Detroit | Michigan |
United States | City of Hope | Duarte | California |
United States | University of Texas MD Anderson Cancer Center | Houston | Texas |
United States | University of California Irvine College of Medicine | Irvine | California |
United States | Memorial Sloan Kettering Cancer Center | New York | New York |
United States | Fox Chase Cancer Center | Philadelphia | Pennsylvania |
United States | Washington University | Saint Louis | Missouri |
United States | University of California San Diego Moores Cancer Center | San Diego | California |
United States | Florida Cancer Center | Sarasota | Florida |
United States | University of Washington, Seattle Cancer Care Alliance | Seattle | Washington |
United States | Lombardi Comprehensive Cancer Center, Georgetown | Washington | District of Columbia |
Lead Sponsor | Collaborator |
---|---|
Hoffmann-La Roche |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Phase 1: Dose Limiting Toxicities | From signing of the informed consent up to approximately 12 months | Approximately 12 months | |
Primary | Phase 1: Occurrence of Adverse Events | From signing of the informed consent up to approximately 12 months | Approximately 12 months | |
Primary | Phase 1b: Occurrence of Adverse Events | To further assess the safety profile and tolerability of RXDX-105 at the RP2D | Approximately 12 months | |
Secondary | Phase 1: Maximum observed plasma drug concentration (Cmax) | Day 1 to Day 16 | ||
Secondary | Phase 1: Time of maximum observed plasma drug concentration (tmax) | Day 1 to Day 16 | ||
Secondary | Phase 1: Area under the plasma drug concentration versus time curve from time 0 to infinity (AUC0-8) | Day 1 to Day 16 | ||
Secondary | Phase 1: Area under the plasma drug concentration versus time curve from time 0 to the last measureable drug concentration (AUC0-t) | Day 1 to Day 16 | ||
Secondary | Phase 1: Area under the plasma drug concentration versus time curve from time 0 to 24 hours after study drug administration (AUC0-24) | Day 1 to Day 16 | ||
Secondary | Phase 1: Terminal elimination rate constant (?z) | Day 1 to Day 16 | ||
Secondary | Phase 1: Terminal elimination half-life (t1/2) | Day 1 to Day 16 | ||
Secondary | Phase 1: Apparent clearance of study drug from plasma (CL/F) | Day 1 to Day 16 | ||
Secondary | 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 | Approximately 12 months | |
Secondary | 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 | Approximately 12 months | |
Secondary | 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 | Approximately 12 months |
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