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

A Multicenter, Open-Label, Phase 2 Study to Determine the Dose, Safety and Efficacy of NKTR-102 (PEG-Irinotecan) in Combination With Cetuximab in Patients With Solid Tumors Refractory to Standard Treatment and to Evaluate the Safety and Efficacy of NKTR-102 or Irinotecan in Combination With Cetuximab in Second Line, Irinotecan and Cetuximab Naïve, Colorectal Cancer Patients With Metastatic or Locally Advanced Disease

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.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer; Tumor
• Intervention / Treatment: Drug: NKTR-102 100 mg/m2; Drug: Cetuximab; Drug: NKTR-102 125 mg/m2

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 Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Investigator Site - Scottsdale
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Investigator Site - Louisville
  • Texas
    • Dallas, Texas, United States, 75426
      • Investigator Site - Dallas
    • Tyler, Texas, United States, 75702
      • Investigator Site - Tyler

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: NKTR-102 100 mg/m2 + 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.	Drug: 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.; Other Names: PEG-Irinotecan; Drug: Cetuximab; 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.; Other Names: Erbitux
Active Comparator: NKTR-102 125 mg/m2 + 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.	Drug: Cetuximab; 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.; Other Names: Erbitux; Drug: 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.; Other Names: PEG-Irinotecan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients With Dose Limiting Toxicities	Number of patients with Dose Limiting Toxicities	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients With Dose Limiting Toxicities by NCI-CTCAE	Number of patients with Dose Limiting Toxicities by NCI-CTCAE	12 months
Number of Patients With Overall Response	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).	12 months

Collaborators and Investigators

• Sponsor: Nektar Therapeutics

Study record dates

Study Major Dates

• Study Start: February 1, 2008
• Primary Completion (Actual): May 1, 2009
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: January 11, 2008
• First Submitted That Met QC Criteria: January 22, 2008
• First Posted (Estimate): January 23, 2008

Study Record Updates

• Last Update Posted (Actual): July 12, 2021
• Last Update Submitted That Met QC Criteria: July 9, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Phase 2a: Multiple solid tumor types; Phase 2b: Second-Line Colorectal Cancer (CRC)
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Topoisomerase I Inhibitors; Irinotecan; Cetuximab; Etirinotecan pegol
• Other Study ID Numbers: 07-PIR-02