A Study of Vantictumab (OMP-18R5) in Combination With Docetaxel in Patients With Previously Treated NSCLC

A Phase 1b Study of Vantictumab (OMP-18R5) in Combination With Docetaxel in Patients With Previously Treated Non-Small Cell Lung Cancer

This is an open-label Phase 1b dose-escalation study to assess the safety, tolerability, and PK of vantictumab when combined with docetaxel.

Study Overview

• Status: Completed
• Conditions: Solid Tumors
• Intervention / Treatment: Drug: Docetaxel; Drug: vantictumab

Detailed Description

Once the maximum tolerated dose (MTD) or maximum administered dose (MAD) has been determined, up to 10 patients may be enrolled in the cohort-expansion phase to better characterize the safety, tolerability and PK of vantictumab combined with docetaxel. Up to approximately 34 patients may be enrolled into the study.

• Study Type: Interventional
• Enrollment (Anticipated): 34
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Center, Elm & Carlton Streets
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Signed Informed Consent Form
• Age ≥18 years
• Histologically documented recurrent or advanced (Stage IV) NSCLC
• Eastern CooperativeOncology Group (ECOG) performance status of 0 or 1
• All acute treatmentrelated toxicity from prior therapy must have resolved to Grade ≤ 1 prior to study entry
• Adequate hematologic and end-organ function
• Evaluable or measurable disease per RECIST v1.1
• For women of childbearing potential and men with partners of childbearing potential, agreement to use two effective forms of contraception

Exclusion Criteria:

• Prior treatment with docetaxel for recurrent or advanced NSCLC
• More than two regimens of systemic cytotoxic chemotherapy for recurrent or advanced NSCLC
• Treatment with any anti-cancer therapy within 3 weeks prior to initiation of study treatment
• Known hypersensitivity to any component of study treatments
• Grade ≥ 2 sensory neuropathy
• Uncontrolled seizure disorder or active neurologic disease
• Untreated brain metastases
• Leptomeningeal disease as a manifestation of cancer
• Active infection requiring antibiotics
• Bisphosphonate therapy for symptomatic hypercalcemia
• Known history of clinically significant liver disease, including active viral hepatitis and cirrhosis
• Significant intercurrent illness including, but not limited to, unstable angina pectoris, and cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements
• Pregnancy, lactation, or breastfeeding
• Known HIV infection
• Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
• Concurrent use of therapeutic warfarin
• New York Heart Association Classification III or IV (see Appendix E)
• Known clinically significant gastrointestinal disease including, but not limited to, inflammatory bowel disease
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to the first dose of study treatment or anticipation of need for major surgical procedure during the course of the study
• Osteoporosis based on a T-score of <-2.5 at the left or right total hip, left or right femoral neck or lumbar spine (L1-L4) as determined by DEXA scan

• Bone metastases and one of the following:

  • Prior history of a pathologic fracture
  • Lytic lesion requiring an impending orthopedic intervention
  • Lack of treatment with a bisphosphonate or denosumab
• Treatment with a thiazolidinedione PPAR gamma inhibitor; e.g. Actos® (pioglitazone), and Avandia® (rosiglitzone)
• Active treatment with an oral or IV glucocortocoid for ≥4 weeks at a daily dose equivalent to or greater than 7.5 mg of oral prednisone
• Fasting β-CTX of >1000 pg/mL
• Metabolic bone disease, such as hyperparathyroidism, Paget's disease or osteomalacia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Docetaxel; Drug: Docetaxel - administered intravenously	Drug: Docetaxel; Docetaxel will be administered IV.; Drug: vantictumab; Vantictumab will be administered intravenously; Other Names: (OMP-18R5)
EXPERIMENTAL: vantictumab; Drug: vantictumab - administered intravenously	Drug: Docetaxel; Docetaxel will be administered IV.; Drug: vantictumab; Vantictumab will be administered intravenously; Other Names: (OMP-18R5)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety and tolerability of vantictumab in combination with docetaxel in patients with recurrent or advanced NSCLC. The maximum tolerated dose (MTD) will be determined in patients treated with vantictumab in combination with weekly paclitaxel.	Subjects will be treated and observed for DLT through the end of the first cycle (Days 0-28)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK) of vantictumab when administered in combination with docetaxel to patients with recurrent or advanced NSCLC	Apparent half life, AUC, clearance, volume of distribution	Plasma sample for Pharmacokinetics (PK) analysis to be obtained prior to the vantictumab infusion and before docetaxel infusion from Day 0 to treatment termination

Collaborators and Investigators

• Sponsor: OncoMed Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start: September 1, 2013
• Primary Completion (ACTUAL): December 1, 2016
• Study Completion (ACTUAL): June 1, 2017

Study Registration Dates

• First Submitted: September 27, 2013
• First Submitted That Met QC Criteria: October 4, 2013
• First Posted (ESTIMATE): October 8, 2013

Study Record Updates

• Last Update Posted (ACTUAL): September 9, 2020
• Last Update Submitted That Met QC Criteria: September 7, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: Phase 1; dose escalation; histologically confirmed; malignancy metastatic
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel
• Other Study ID Numbers: 18R5-004