Conditions: Tumor Colorectal Cancer
Keywords: Phase 2a: Multiple solid tumor types Phase 2b: Second-Line Colorectal Cancer (CRC)
Allocation: NON_RANDOMIZED | Intervention model: PARALLEL
Enrollment: 18
Healthy volunteers: no

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.

Arms:
arm 1: 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. arm 2: 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.

Interventions: intervention 1: NKTR-102 100 mg/m2 intervention 2: NKTR-102 125 mg/m2 intervention 3: Cetuximab
Intervention descriptions: intervention 1: 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. intervention 2: 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. intervention 3: Cetuximab was administered once weekly via a 2-hour IV infusion at a starting dose of 400 mg/m2 on Day 1 and subsequently administered weekly at 250 mg/m2 via a 1-hour infusion thereafter.

Protocol document: