Study of Intravenous RXDX-107 in Patients With Solid Tumors
Study Details
Study Description
Brief Summary
This is an open-label, Phase I/Ib, dose escalation study of intravenous RXDX-107 administered to subjects with advanced solid tumors. The study is designed to explore the safety, maximum tolerated dose (MTD), pharmacokinetics, pharmacodynamics, and preliminary clinical activity of RXDX-107 and to define a recommended Phase 2 dose (RP2D)
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: RXDX-107
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Drug: RXDX-107
Subjects in this study will receive RXDX-107 intravenously at dose levels specified for their respective dose cohorts. Dosing will begin at 25 mg/m2 on Day 1 and Day 2 of a 28-day cycle and will escalate until the maximum tolerated dose (MTD) or (RP2D) is determined. An additional schedule of administration of RXDX-107 on Day 1 of a 28 day cycle may be assessed. Cycles will be repeated in four-week (28 day) intervals for up to 6 cycles or until progression of disease, unacceptable toxicity, or another discontinuation criterion is met.
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Outcome Measures
Primary Outcome Measures
- Phase 1: Safety profile of RXDX-107 as characterized by Adverse Events, ECG and laboratory abnormalities [Approx. 1 year]
AEs, ECG and Labs assessed according to NCI CTCAE V4.0
- Phase 1: Maximum observed plasma drug concentration (Cmax) [Approx. 1 year]
Plasma concentrations obtained following the dose on Day 1 (and from the dose on Day 2 in patients receiving the Day 1 and Day 2 schedule)
- Phase 1: Time to Cmax, by inspection (tmax) [Approx. 1 year]
Plasma concentrations obtained following the dose on Day 1 (and from the dose on Day 2 in patients receiving the Day 1 and Day 2 schedule)
- Phase 1: Area under the drug concentration by time curve (AUC) [Approx. 1 year]
From time 0 to the time of the last detectable plasma concentration (AUC0-t)
- Phase 1: Apparent plasma terminal elimination rate constant (λz) and associated terminal half life (t½) [Approx. 1 year]
Plasma concentrations obtained following the dose on Day 1 (and from the dose on Day 2 in patients receiving the Day 1 and Day 2 schedule)
- Phase 1: Plasma clearance (CL) [Approx. 1 year]
Plasma concentrations obtained following the dose on Day 1 (and from the dose on Day 2 in patients receiving the Day 1 and Day 2 schedule)
- Phase 1: Volume of distribution (Vz) [Approx. 1 year]
Plasma concentrations obtained following the dose on Day 1 (and from the dose on Day 2 in patients receiving the Day 1 and Day 2 schedule)
- Phase 1: Maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) [Approx. 6 months]
- Phase 1b: Confirm RP2D [Approx. 1 year]
Number of participants with Treatment-related AEs, Labs changes from baseline, and QTc interval changes from baseline assessed according to NCI CTCAE V4.0, concomitant medication usage, including all supportive care provided, and preliminary anti-tumor activity per RECIST v1.1 as assessed by Investigator
Secondary Outcome Measures
- Antitumor activity of RXDX-107 as measured by Objective Response Rate (ORR) [Approx. 1 year]
Per RECIST v1.1 as assessed by Investigator
Eligibility Criteria
Criteria
Inclusion Criteria:
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Confirmed relapsed or refractory locally advanced or metastatic solid cancer for whom no standard therapy is considered appropriate, or for whom standard therapy is considered intolerable.
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18 years of age.
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ECOG performance status of 0 or 1.
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Life expectancy of at least 3 months.
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Received the last dose of previous treatment / therapy before Day 1 of cycle 1:
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28 days for cytotoxic chemotherapy, immunotherapy, whole brain radiotherapy, anticonvulsive therapy, stereotactic radiosurgery and major surgery
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42 days for nitrosureas, mitomycin C, and liposomal anthracycline
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14 days for non-cytotoxic cancer therapies and radiotherapy
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Recovered from all toxic effects (excluding alopecia) of any prior anti-cancer therapy to Grade ≤ 1 or to the baseline laboratory values.
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Adequate organ function and baseline laboratory values
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Women of childbearing potential must have a negative serum pregnancy
Phase 1b: Patient must have measurable disease
Exclusion Criteria:
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Receiving other experimental therapy
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Known symptomatic brain mets or leptomeningeal involvement
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Myocardial infarction in the previous 12 weeks. Active ischemia or any other uncontrolled cardiac condition such as angina pectoris, significant cardiac arrhythmia requiring therapy, uncontrolled hypertension, or CHF.
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Another concurrent illness which would preclude study conduct and assessment, uncontrolled: medical condition, active infection, risk of bleeding, diabetes mellitus, or pulmonary disease, or alcoholic liver disease, or primary biliary cirrhosis.
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Malignancy within 3 years or active disease requiring treatment other than the target cancer. The exceptions are prostate cancer (Gleason grade < 6 with normalized PSA levels), treated in situ cervical, breast carcinoma, squamous or basal cell skin cancer.
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Any condition that may compromise the ability to give written informed consent or to comply with the study protocol.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Florida Cancer Specialists | Sarasota | Florida | United States | 34232 |
2 | Johns Hopkins Medical Institute | Baltimore | Maryland | United States | 21205 |
3 | Tennessee Oncology, LLC | Nashville | Tennessee | United States | 37203 |
Sponsors and Collaborators
- Hoffmann-La Roche
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- RXDX-107-01