NKTR-102 Versus Irinotecan in Patients With Second-Line, Irinotecan-Naïve, KRAS Mutant, Colorectal Cancer

Colorectal Cancer Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00856375
• Other study ID #: 08-PIR-03
• Status: Completed
• Phase: Phase 2
• Start date: December 2008
• Est. completion date: December 2014

Study information

• Verified date: July 2021
• Source: Nektar Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 83
• Est. completion date: December 2014
• Est. primary completion date: July 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• metastatic colorectal cancer

• tumor with k-ras mutation

Exclusion Criteria:

• More than 1 prior regimen for treatment of metastatic disease

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Drug:
• NKTR-102
IV every 3 weeks
• irinotecan
IV every 3 weeks

Locations

Country	Name	City	State
Belgium	Investigator Site - Antwerp	Antwerp
Germany	Investigator Site - Celle	Celle
Germany	Investigator Site - Karlsruhe	Karlsruhe
India	Investigator Site - Ahmedabad	Ahmedabad	Gujarat
India	Investigator Site - Bangalore	Bangalore	Karnatak
India	Investigator Site - Bangalore	Bangalore	Karnatak
India	Investigator Site - Hyderabad	Hyderabad	Andra Pradesh
India	Investigator Site - Kochi	Kochi	Kerata
India	Investigator Site - Kolkata	Kolkata	West Benagal
India	Investigator Site - Kolkata	Kolkata	West Bengal
India	Investigator Site - Mumbai	Mumbai	Maharashtra
Spain	Investigator Site - Elche	Elche
Spain	Investigator Site - Madrid	Madrid
United Kingdom	Investigator Site - Aberdeen	Aberdeen	Scotland
United Kingdom	Investigator Site - Manchester	Manchester
United States	Investigator Site - Buffalo	Buffalo	New York
United States	Investigator Site - Burbank	Burbank	California
United States	Investigator Site - Centralia	Centralia	Illinois
United States	Investigator Site - Detroit	Detroit	Michigan
United States	Investigator Site - Knoxville	Knoxville	Tennessee
United States	Investigator Site - Los Angeles	Los Angeles	California
United States	Investigator Site - Louisville	Louisville	Kentucky
United States	Investigator Site - Peoria	Peoria	Arizona
United States	Investigator Site - Vallejo	Vallejo	California

Sponsors (1)

Lead Sponsor	Collaborator
Nektar Therapeutics

Countries where clinical trial is conducted

United States,  Belgium,  Germany,  India,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Kaplan-Meier Estimate of PFS by Central Radiological Review: ITT Population	PFS was defined as the time from the date of randomisation to the date of disease progression (assessed by central radiological review according to Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) or death due to any cause, whichever comes first. PFS was determined using the intention-to-treat (ITT) population which included all randomized patients who underwent baseline evaluation, with treatment assigned according to randomized arm. For patients whose disease did not progress or who did not die, the PFS time was censored at the time of the last tumor assessment that demonstrated lack of disease progression. For patients who received new anti-cancer therapy, the PFS time was censored at the time of last tumor assessment prior to the new anti-cancer therapy starts.	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	Kaplan-Meier Estimate of OS: ITT Population	Duration of OS was defined as the time from the date of randomization to the date of death due to any cause. Patients were followed until their date of death, loss to follow-up, withdrawal of consent for further follow-up for survival, or final database closure. Patients who were lost-to-follow-up or were not known to have died were censored at last date they were shown to be alive. Patients who did not have any follow-up since the date of randomization were censored at the date of randomization.	From randomization to death, loss to follow-up, withdrawal of consent for further follow-up for survival, or end of study, approximately 42 months.
Secondary	ORR by Central Radiological Review: ITT Population	ORR was defined as the proportion of patients with a complete response (CR) or a partial response (PR) per RECIST 1.1 based upon the best response as assessed by central radiological review; confirmation of response was not required. The analyses were performed for patients in the ITT population who had measurable disease as determined by the central imaging facility at baseline.	From randomization of the first subject until documented disease progression, start of new therapy for cancer, death, or end of study approximately 42 months
Secondary	DoR by Central Radiological Review: ITT Population	Progressive Disease (PD) is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that was the smallest on study); in addition to a relative increase of 20%, the sum must have also demonstrated an absolute increase of at least 5 mm. CR is defined as disappearance of all target lesions; any pathological lymph nodes (whether target or non-target) must have had a reduction in short axis to < 10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters	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
Secondary	Percentage of Participants (=2%) With Treatment-Emergent Adverse Events NCI-CTCAE Grade 3 or Higher	An adverse event (AE) was any untoward medical occurrence in a patient administered a pharmaceutical product which did not necessarily have a causal relationship with the treatment. An AE could have been any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Pre-existing events, which increased in frequency or severity or changed in nature during or as a consequence of use of the study medication were also considered as AEs. All AEs were assessed for severity using the National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 3.0. If a particular AE was not listed in the NCI CTCAE Version 3.0, the following criteria were used: Grade 3 = severe; Grade 4 = life threatening or disabling; Grade 5 = death.	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
Secondary	PK Parameters of NKTR-102 or Irinotecan and Respective Metabolites	Blood samples for PK analysis were collected from 4 patients only, 3 from the irinotecan treatment arm and 1 from the NKTR-102 treatment arm. NKTR-102, irinotecan, SN38, SN38-G, 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino]carbonyloxycamptothecin, and 7-ethyl-10-(4-amino-1-piperidino) carbonyloxycamptothecin concentration levels were determined. However, due to the limited number of patients with PK samples, no further PK analysis was conducted.	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.