A Study of LCL161 in Combination With Weekly Paclitaxel in Adult Patients With Advanced Solid Tumors

A Phase Ib Study of LCL161 in Combination With Weekly Paclitaxel in Adult Patients With Advanced Solid Tumors

This is a dose escalation study that will assess the safety and efficacy of LCL161 in combination with weekly paclitaxel in adult patients with advanced solid tumors.

Study Overview

• Status: Completed
• Conditions: Solid Tumors
• Intervention / Treatment: Drug: Paclitaxel; Drug: LCL161

• Study Type: Interventional
• Enrollment (Actual): 76
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1L3
      • Novartis Investigative Site
• Italy
  • MO
    • Modena, MO, Italy, 41100
      • Novartis Investigative Site
• Spain
  • Catalunya
    • Barcelona, Catalunya, Spain, 08035
      • Novartis Investigative Site
    • Barcelona, Catalunya, Spain, 08036
      • Novartis Investigative Site
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute SC
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • University of North Carolina Lineberger Comp Cancer Ctr
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute DeptofSarahCannonRes.Inst. (2)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Patients with breast cancer must have a histologically or cytologically confirmed diagnosis of disease that has metastasized or is resistant to therapy.

Patients with ovarian cancer must have histological evidence of recurrent epithelial ovarian, fallopian tube or peritoneal cancer.

Patients must have recovered or stabilized from all toxicities related to their previous treatment except for alopecia Male or female patients 18 years or older ECOG performance status 0-1 Life expectancy greater than 12 weeks Measurable disease as determined by RECIST v1.0 Patients must give written informed consent and comply with the protocol

Exclusion Criteria:

For patients with breast cancer:

Concurrent Her2-directed or anti-estrogen therapy

For patients with ovarian cancer:

Primary refractory disease, defined as progression during initial treatment with a platinum- and taxane-containing regimen.

Prior treatment with weekly paclitaxel. More than two chemotherapy regimens given in the relapse setting. Evidence of a documented bowel obstruction within six months of study entry Patients with unresolved peripheral neuropathy, nausea, vomiting, or diarrhea ≥ CTCAE Grade 2 Any concurrent severe and/or uncontrolled medical conditions that could increase the patient's risk for toxicity while in the study or that could confound discrimination between disease- and study treatment-related toxicities.

Patients with impairment of GI function or GI disease that may significantly alter the absorption of LCL161 Patients who have undergone major surgery ≤ 3 weeks prior to starting study drug or who have not recovered from side effects of procedure.

Pregnant or breast feeding (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive β-HCG laboratory test (> 5 mIU/mL).

Known diagnosis of human immunodeficiency virus (HIV) infection or chronic active hepatitis B or C (HIV and hepatitis testing are not mandatory).

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: LCL161 + Paclitaxel	Drug: Paclitaxel; Drug: LCL161

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum tolerated dose (MTD)/RP2D of LCL161 when administered in combination with once weekly paclitaxel	24 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Safety and tolerability of the combination, including acute and chronic toxicities	24 months
Pharmacokinetics of both LCL161 and paclitaxel when administered in combination (AUC0-∞, Cmax, tmax and other parameters as appropriate)	24 months
Preliminary anti-tumor activity associated with this combination treatment	24 months
Target inhibition, cell death, and cytokines in surrogate and tumor tissues	24 months

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• Results for CLCL161A2104can be found on the Novartis Clinical Trial Results Website

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (ACTUAL): January 1, 2015
• Study Completion (ACTUAL): January 1, 2015

Study Registration Dates

• First Submitted: November 10, 2010
• First Submitted That Met QC Criteria: November 12, 2010
• First Posted (ESTIMATE): November 15, 2010

Study Record Updates

• Last Update Posted (ACTUAL): December 19, 2020
• Last Update Submitted That Met QC Criteria: December 16, 2020
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: paclitaxel; solid tumors; LCL161
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel
• Other Study ID Numbers: CLCL161A2104; 2009-015594-12 (EUDRACT_NUMBER)