Clinical trial NCT00856375: NKTR-102 Versus Irinotecan in Patients With Second-Line, Irinotecan-Naïve, KRAS Mutant, Colorectal Cancer
Official title: A Multicenter, Open-Label, Randomized, Phase 2 Study to Evaluate the Efficacy and Safety of NKTR-102 Versus Irinotecan in Patients With Second-Line, Irinotecan-Naive, KRAS-Mutant, Metastatic Colorectal Cancer (mCRC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Cancer
Keywords: colorectal cancer
Colorectal cancer, second line
Lead sponsor: Nektar Therapeutics
Sponsor class: INDUSTRY
First posted: 2009-03-05
Enrollment: 83
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will evaluate whether NKTR-102, an investigational drug has an anti-tumor effect in patients with colorectal cancer. This study will also evaluate how the safety and anti-tumor activity of NKTR-102 compares with irinotecan, a cancer drug that is approved for use in the US for treatment of patients with certain types of colorectal cancer.

Detailed description: NKTR-102 (Topoisomerase I Inhibitor Polymer Conjugate) is a polyethylene glycol (PEG) conjugate of irinotecan. Irinotecan is a topoisomerase I inhibitor approved worldwide. In the US, irinotecan is indicated as a component of first-line therapy in combination with 5 fluorouracil (5 FU) and leucovorin for patients with metastatic carcinoma of the colon or rectum. Irinotecan is also indicated for patients with metastatic carcinoma of the colon or rectum whose disease has recurred or progressed following initial fluorouracil-based therapy.

Second-line therapy for colorectal cancer typically involves cetuximab and irinotecan. However, growing evidence indicates that cetuximab (or other EGFR inhibitors) is not appropriate therapy for patients with mutant KRAS. For these patients, irinotecan may be appropriate as a single agent, and a new therapy that could improve upon efficacy and safety would provide an important option for the treatment of advanced colorectal cancer.

Eligibility criteria: Inclusion Criteria:

* metastatic colorectal cancer
* tumor with k-ras mutation

Exclusion Criteria:

* More than 1 prior regimen for treatment of metastatic disease

Primary outcomes:
measure: Kaplan-Meier Estimate of PFS by Central Radiological Review: ITT Population
timeFrame: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study, approximately 42 months.
Secondary outcomes:
measure: Kaplan-Meier Estimate of OS: ITT Population
timeFrame: From randomization to death, loss to follow-up, withdrawal of consent for further follow-up for survival, or end of study, approximately 42 months.
measure: ORR by Central Radiological Review: ITT Population
timeFrame: From randomization of the first subject until documented disease progression, start of new therapy for cancer, death, or end of study approximately 42 months
measure: DoR by Central Radiological Review: ITT Population
timeFrame: From the time measurement criteria for CR/PR (whichever was first recorded) were first met until the first date that recurrent disease or PD or death was objectively documented, assessed until the end of study approximately 42 months
measure: Percentage of Participants (≥2%) With Treatment-Emergent Adverse Events NCI-CTCAE Grade 3 or Higher
timeFrame: From the first dose of study medication through the End-of-Treatment visit (30 ± 3 days from last dose of study drug), assessed until the end of study approximately 42 months
measure: PK Parameters of NKTR-102 or Irinotecan and Respective Metabolites
timeFrame: Days 1, 2, 3, 4, 8 and 15 of Cycles 1 and 3 and Day 1 of Cycles 2, 4 and all subsequent cycles, until End of Study, approximately 42 months.
Other outcomes:
Locations:
city: Peoria
country: United States
facility: Investigator Site - Peoria
state: Arizona
city: Burbank
country: United States
facility: Investigator Site - Burbank
state: California
city: Los Angeles
country: United States
facility: Investigator Site - Los Angeles
state: California
city: Vallejo
country: United States
facility: Investigator Site - Vallejo
state: California
city: Centralia
country: United States
facility: Investigator Site - Centralia
state: Illinois
city: Louisville
country: United States
facility: Investigator Site - Louisville
state: Kentucky
city: Detroit
country: United States
facility: Investigator Site - Detroit
state: Michigan
city: Buffalo
country: United States
facility: Investigator Site - Buffalo
state: New York
city: Knoxville
country: United States
facility: Investigator Site - Knoxville
state: Tennessee
city: Antwerp
country: Belgium
facility: Investigator Site - Antwerp
city: Celle
country: Germany
facility: Investigator Site - Celle
city: Karlsruhe
country: Germany
facility: Investigator Site - Karlsruhe
city: Hyderabad
country: India
facility: Investigator Site - Hyderabad
state: Andra Pradesh
city: Ahmedabad
country: India
facility: Investigator Site - Ahmedabad
state: Gujarat
city: Bangalore
country: India
facility: Investigator Site - Bangalore
state: Karnatak
city: Bangalore
country: India
facility: Investigator Site - Bangalore
state: Karnatak
city: Kochi
country: India
facility: Investigator Site - Kochi
state: Kerata
city: Mumbai
country: India
facility: Investigator Site - Mumbai
state: Maharashtra
city: Kolkata
country: India
facility: Investigator Site - Kolkata
state: West Benagal
city: Kolkata
country: India
facility: Investigator Site - Kolkata
state: West Bengal
city: Elche
country: Spain
facility: Investigator Site - Elche
city: Madrid
country: Spain
facility: Investigator Site - Madrid
city: Aberdeen
country: United Kingdom
facility: Investigator Site - Aberdeen
state: Scotland
city: Manchester
country: United Kingdom
facility: Investigator Site - Manchester
Study officials:
affiliation: Nektar Therapeutics
name: Study Director
role: STUDY_DIRECTOR
References: