Study of Intravenous RXDX-107 in Patients With Solid Tumors

A Phase 1/1b, Multicenter, Open-Label Study of Intravenous RXDX-107 in Adult Patients With Locally Advanced or Metastatic Solid Cancer

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)

Study Overview

• Status: Terminated
• Conditions: Solid Tumor
• Intervention / Treatment: Drug: RXDX-107

• Study Type: Interventional
• Enrollment (Anticipated): 70
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Sarasota, Florida, United States, 34232
      • Florida Cancer Specialists
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins Medical Institute
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: RXDX-107

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: Safety profile of RXDX-107 as characterized by Adverse Events, ECG and laboratory abnormalities	AEs, ECG and Labs assessed according to NCI CTCAE V4.0	Approx. 1 year
Phase 1: Maximum observed plasma drug concentration (Cmax)	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)	Approx. 1 year
Phase 1: Time to Cmax, by inspection (tmax)	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)	Approx. 1 year
Phase 1: Area under the drug concentration by time curve (AUC)	From time 0 to the time of the last detectable plasma concentration (AUC0-t)	Approx. 1 year
Phase 1: Apparent plasma terminal elimination rate constant (λz) and associated terminal half life (t½)	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)	Approx. 1 year
Phase 1: Plasma clearance (CL)	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)	Approx. 1 year
Phase 1: Volume of distribution (Vz)	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)	Approx. 1 year
Phase 1: Maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D)		Approx. 6 months
Phase 1b: Confirm RP2D	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	Approx. 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Antitumor activity of RXDX-107 as measured by Objective Response Rate (ORR)	Per RECIST v1.1 as assessed by Investigator	Approx. 1 year

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: September 1, 2015
• Primary Completion (Actual): September 1, 2016
• Study Completion (Actual): September 1, 2016

Study Registration Dates

• First Submitted: September 9, 2015
• First Submitted That Met QC Criteria: September 10, 2015
• First Posted (Estimate): September 14, 2015

Study Record Updates

• Last Update Posted (Actual): April 25, 2019
• Last Update Submitted That Met QC Criteria: April 24, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: chemotherapy; pharmacokinetics; open-label; metastatic cancer; solid tumor; dose-escalation; Phase 1/1b; nano formulation; alkylator
• Other Study ID Numbers: RXDX-107-01