Clinical trial NCT01240655: A Study of LCL161 in Combination With Weekly Paclitaxel in Adult Patients With Advanced Solid Tumors
Official title: A Phase Ib Study of LCL161 in Combination With Weekly Paclitaxel in Adult Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumors
Keywords: LCL161
solid tumors
paclitaxel
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2010-11-15
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Maximum tolerated dose (MTD)/RP2D of LCL161 when administered in combination with once weekly paclitaxel
timeFrame: 24 months
Secondary outcomes:
measure: Safety and tolerability of the combination, including acute and chronic toxicities
timeFrame: 24 months
measure: Pharmacokinetics of both LCL161 and paclitaxel when administered in combination (AUC0-∞, Cmax, tmax and other parameters as appropriate)
timeFrame: 24 months
measure: Preliminary anti-tumor activity associated with this combination treatment
timeFrame: 24 months
measure: Target inhibition, cell death, and cytokines in surrogate and tumor tissues
timeFrame: 24 months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana Farber Cancer Institute SC
state: Massachusetts
city: Chapel Hill
country: United States
facility: University of North Carolina Lineberger Comp Cancer Ctr
state: North Carolina
city: Nashville
country: United States
facility: Sarah Cannon Research Institute DeptofSarahCannonRes.Inst. (2)
state: Tennessee
city: Vancouver
country: Canada
facility: Novartis Investigative Site
state: British Columbia
city: Modena
country: Italy
facility: Novartis Investigative Site
state: MO
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: