NKTR-102 in Combination With Cetuximab in Patients With Refractory Solid Tumors (Phase 2a) and Metastatic or Locally Advanced Colorectal Cancer (Phase 2b)

Phase 2

Completed

• Conditions: Tumor; Colorectal Cancer
• Interventions: Drug: NKTR-102 100 mg/m2; Drug: NKTR-102 125 mg/m2; Drug: Cetuximab

• Registration Number: NCT00598975
• Lead Sponsor: Nektar Therapeutics

Brief Summary

Study 07-PIR-02 is a Phase 2 study designed to evaluate the safety and efficacy of NKTR-102 (PEG-irinotecan) for the treatment of patients with colorectal cancer (CRC). The study is comprised of two sequential components - Phase 2a and Phase 2b. The Phase 2a portion is an open-label, dose-finding trial in multiple solid tumor types that are refractory to standard curative or palliative therapies. The primary endpoint of the Phase 2a is to establish the /recommended Phase 2 Dose (RPTD) of NKTR-102 by measuring the frequency of Dose Limiting Toxicity (DLT). The Phase 2b portion is an open-label, randomized, two-arm study in patients with second-line metastatic colorectal cancer and study participants will be randomized (1:1) to receive either NKTR-102 and cetuximab or irinotecan and cetuximab. The primary endpoint of the Phase 2b portion of the trial is progression-free survival. Secondary endpoints for both the Phase 2a and 2b portion include response rate, response duration, overall survival, standard pharmacokinetics, and incidence of toxicities, including diarrhea and neutropenia.

Detailed Description

The Phase 2a portion of this study is completed. The following entries reflect the Phase 2a portion of this study only. The Phase 2b portion of the study was not enrolled. Based on emerging data regarding the corresponding low efficacy of cetuximab in patients with KRAS mutations, as well as revised NKTR-102 clinical development plans, the Phase 2b portion of the study was not completed.

Study Timeline

• Study First Submitted: 2008-01-11
• Study First Submitted QC: 2008-01-22
• Study First Posted: 2008-01-23
• Study Start: 2008-02
• Primary Completion: 2009-05
• Study Completion: 2011-12
• Disposition First Submitted: 2014-08-12
• Disposition First Submitted QC: 2014-08-12
• Disposition First Posted: 2014-08-15
• Results First Submitted: 2018-01-30
• Results First Submitted QC: 2021-05-18
• Results First Posted: 2021-06-14
• Status Verified: 2021-07
• Last Update Submitted: 2021-07-09
• Last Update Posted: 2021-07-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 18

Inclusion Criteria

• Male and non-pregnant, non-lactating female patients with an ECOG performance score <3 who have any type of solid tumor refractory to standard therapy and who have adequate bone marrow and organ function at screening.

Exclusion Criteria

• Patients must not have used any CYP3A4 inducers or inhibitors with 2 weeks prior to the first day of study drug treatment.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
NKTR-102 100 mg/m2 + Cetuximab	NKTR-102 100 mg/m2	NKTR-102 100 mg/m2 + Cetuximab Arm All patients received NKTR-102 in combination with cetuximab. NKTR-102 was administered intravenously (IV) once every 3 weeks (q3w) over 90 minutes on Day 1. Patients were to be enrolled in one of the following sequential dosing cohorts of NKTR-102: 100, 125, 150, or 175 mg/m2. Only the 100 and 125 mg/m2 were enrolled.
NKTR-102 100 mg/m2 + Cetuximab	Cetuximab	NKTR-102 100 mg/m2 + Cetuximab Arm All patients received NKTR-102 in combination with cetuximab. NKTR-102 was administered intravenously (IV) once every 3 weeks (q3w) over 90 minutes on Day 1. Patients were to be enrolled in one of the following sequential dosing cohorts of NKTR-102: 100, 125, 150, or 175 mg/m2. Only the 100 and 125 mg/m2 were enrolled.
NKTR-102 125 mg/m2 + Cetuximab	NKTR-102 125 mg/m2	NKTR-102 125 mg/m2 + Cetuximab Arm All patients received NKTR-102 in combination with cetuximab. NKTR-102 was administered intravenously (IV) once every 3 weeks (q3w) over 90 minutes on Day 1. Patients were to be enrolled in one of the following sequential dosing cohorts of NKTR-102: 100, 125, 150, or 175 mg/m2. Only the 100 and 125 mg/m2 were enrolled.
NKTR-102 125 mg/m2 + Cetuximab	Cetuximab	NKTR-102 125 mg/m2 + Cetuximab Arm All patients received NKTR-102 in combination with cetuximab. NKTR-102 was administered intravenously (IV) once every 3 weeks (q3w) over 90 minutes on Day 1. Patients were to be enrolled in one of the following sequential dosing cohorts of NKTR-102: 100, 125, 150, or 175 mg/m2. Only the 100 and 125 mg/m2 were enrolled.

Primary Outcome Measures

Name	Time	Method
Number of Patients With Dose Limiting Toxicities	12 months	Number of patients with Dose Limiting Toxicities

Secondary Outcome Measures

Name	Time	Method
Number of Patients With Overall Response	12 months	Complete Response is defined as the disappearance of all target lesions. Partial Response is defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter. The best overall response was the best response recorded from the start of the study drug until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started).
Number of Patients With Dose Limiting Toxicities by NCI-CTCAE	12 months	Number of patients with Dose Limiting Toxicities by NCI-CTCAE

Trial Locations

Locations (4)

Investigator Site - Scottsdale; 🇺🇸 Scottsdale, Arizona, United States

Investigator Site - Tyler; 🇺🇸 Tyler, Texas, United States

Investigator Site - Louisville; 🇺🇸 Louisville, Kentucky, United States

Investigator Site - Dallas; 🇺🇸 Dallas, Texas, United States