Clinical trial NCT02548390: Study of Intravenous RXDX-107 in Patients With Solid Tumors
Official title: A Phase 1/1b, Multicenter, Open-Label Study of Intravenous RXDX-107 in Adult Patients With Locally Advanced or Metastatic Solid Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Solid Tumor
Keywords: Phase 1/1b
open-label
dose-escalation
pharmacokinetics
solid tumor
metastatic cancer
chemotherapy
nano formulation
alkylator
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2015-09-14
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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)


Eligibility criteria: Inclusion Criteria:

1. 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.
2. \>18 years of age.
3. ECOG performance status of 0 or 1.
4. Life expectancy of at least 3 months.
5. Received the last dose of previous treatment / therapy before Day 1 of cycle 1:

   * 28 days for cytotoxic chemotherapy, immunotherapy, whole brain radiotherapy, anticonvulsive therapy, stereotactic radiosurgery and major surgery
   * 42 days for nitrosureas, mitomycin C, and liposomal anthracycline
   * 14 days for non-cytotoxic cancer therapies and radiotherapy
6. Recovered from all toxic effects (excluding alopecia) of any prior anti-cancer therapy to Grade ≤ 1 or to the baseline laboratory values.
7. Adequate organ function and baseline laboratory values
8. Women of childbearing potential must have a negative serum pregnancy

Phase 1b: Patient must have measurable disease

Exclusion Criteria:

1. Receiving other experimental therapy
2. Known symptomatic brain mets or leptomeningeal involvement
3. 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.
4. 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.
5. 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.
6. Any condition that may compromise the ability to give written informed consent or to comply with the study protocol.

Primary outcomes:
measure: Phase 1: Safety profile of RXDX-107 as characterized by Adverse Events, ECG and laboratory abnormalities
timeFrame: Approx. 1 year
measure: Phase 1: Maximum observed plasma drug concentration (Cmax)
timeFrame: Approx. 1 year
measure: Phase 1: Time to Cmax, by inspection (tmax)
timeFrame: Approx. 1 year
measure: Phase 1: Area under the drug concentration by time curve (AUC)
timeFrame: Approx. 1 year
measure: Phase 1: Apparent plasma terminal elimination rate constant (λz) and associated terminal half life (t½)
timeFrame: Approx. 1 year
measure: Phase 1: Plasma clearance (CL)
timeFrame: Approx. 1 year
measure: Phase 1: Volume of distribution (Vz)
timeFrame: Approx. 1 year
measure: Phase 1: Maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D)
timeFrame: Approx. 6 months
measure: Phase 1b: Confirm RP2D
timeFrame: Approx. 1 year
Secondary outcomes:
measure: Antitumor activity of RXDX-107 as measured by Objective Response Rate (ORR)
timeFrame: Approx. 1 year
Other outcomes:
Locations:
city: Sarasota
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Baltimore
country: United States
facility: Johns Hopkins Medical Institute
state: Maryland
city: Nashville
country: United States
facility: Tennessee Oncology, LLC
state: Tennessee
Study officials:
References: