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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT01240655

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

10.9

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumors	Drug: LCL161 Drug: Paclitaxel	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

76 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Apr 1, 2011

Actual Primary Completion Date :

Jan 1, 2015

Actual Study Completion Date :

Jan 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LCL161 + Paclitaxel	Drug: LCL161 Drug: Paclitaxel

Arm

Intervention/Treatment

Experimental: LCL161 + Paclitaxel

Drug: LCL161

Drug: Paclitaxel

Outcome Measures

Primary Outcome Measures

Maximum tolerated dose (MTD)/RP2D of LCL161 when administered in combination with once weekly paclitaxel [24 months]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 100 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

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