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

• Sponsor: Nektar Therapeutics (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00856375
• Collaborator: (none)
• Enrollment: 83
• Locations: 24
• Arms: 2
• Duration (Months): 72
• Patients Per Site: 3.5
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer	Drug: NKTR-102; Drug: irinotecan	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 83 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: Dec 1, 2008
• Actual Primary Completion Date: Jul 1, 2014
• Actual Study Completion Date: Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: NKTR-102 NKTR-102 IV every 3 weeks	Drug: NKTR-102; IV every 3 weeks; Other Names: etirinotecan pegol
Active Comparator: irinotecan irinotecan IV every 3 weeks	Drug: irinotecan; IV every 3 weeks

Outcome Measures

Primary Outcome Measures

1. Kaplan-Meier Estimate of PFS by Central Radiological Review: ITT Population [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.]

   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.

Secondary Outcome Measures

1. Kaplan-Meier Estimate of OS: ITT Population [From randomization to death, loss to follow-up, withdrawal of consent for further follow-up for survival, or end of study, approximately 42 months.]

   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.

2. ORR by Central Radiological Review: ITT Population [From randomization of the first subject until documented disease progression, start of new therapy for cancer, death, or end of study approximately 42 months]

   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.

3. DoR by Central Radiological Review: ITT Population [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]

   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

4. Percentage of Participants (≥2%) With Treatment-Emergent Adverse Events NCI-CTCAE Grade 3 or Higher [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]

   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.

5. PK Parameters of NKTR-102 or Irinotecan and Respective Metabolites [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.]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• metastatic colorectal cancer

• tumor with k-ras mutation

Exclusion Criteria:

• More than 1 prior regimen for treatment of metastatic disease

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigator Site - Peoria	Peoria	Arizona	United States	85381
2	Investigator Site - Burbank	Burbank	California	United States	91505
3	Investigator Site - Los Angeles	Los Angeles	California	United States	90033
4	Investigator Site - Vallejo	Vallejo	California	United States	94589
5	Investigator Site - Centralia	Centralia	Illinois	United States	62801
6	Investigator Site - Louisville	Louisville	Kentucky	United States	40202
7	Investigator Site - Detroit	Detroit	Michigan	United States	48201
8	Investigator Site - Buffalo	Buffalo	New York	United States	14215
9	Investigator Site - Knoxville	Knoxville	Tennessee	United States	37909
10	Investigator Site - Antwerp	Antwerp		Belgium	2020
11	Investigator Site - Celle	Celle		Germany	29223
12	Investigator Site - Karlsruhe	Karlsruhe		Germany	48201
13	Investigator Site - Hyderabad	Hyderabad	Andra Pradesh	India	500004
14	Investigator Site - Ahmedabad	Ahmedabad	Gujarat	India	380009
15	Investigator Site - Bangalore	Bangalore	Karnatak	India	560054
16	Investigator Site - Bangalore	Bangalore	Karnatak	India	560078
17	Investigator Site - Kochi	Kochi	Kerata	India	682041
18	Investigator Site - Mumbai	Mumbai	Maharashtra	India	91-98-50986003
19	Investigator Site - Kolkata	Kolkata	West Benagal	India	700026
20	Investigator Site - Kolkata	Kolkata	West Bengal	India	700053
21	Investigator Site - Elche	Elche		Spain	34-966-616250
22	Investigator Site - Madrid	Madrid		Spain	28034
23	Investigator Site - Aberdeen	Aberdeen	Scotland	United Kingdom	AB25 2ZN
24	Investigator Site - Manchester	Manchester		United Kingdom	MD20 4BX

Sponsors and Collaborators

• Nektar Therapeutics

Investigators

• Study Director: Study Director, Nektar Therapeutics

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Nektar Therapeutics
• ClinicalTrials.gov Identifier: NCT00856375
• Other Study ID Numbers: 08-PIR-03
• First Posted: Mar 5, 2009
• Last Update Posted: Jul 12, 2021
• Last Verified: Jul 1, 2021

• Keywords provided by Nektar Therapeutics: colorectal cancer; Colorectal cancer, second line
• Additional relevant MeSH terms: Colorectal Neoplasms; Irinotecan; Etirinotecan pegol

Study Results

Participant Flow

Arm/Group Title	NKTR-102	Irinotecan
Arm/Group Description	NKTR-102 was administered as an intravenous (IV) infusion on Day 1 of each 21-day cycle at a dose level of 145 mg/m^2.	Irinotecan was administered as an IV infusion on Day 1 of a 21-day treatment cycle at a dose level of 350 mg/m^2. Patients aged 65 or older, or those with prior abdominal or pelvic irradiation, were given a lower dose of 300 mg/m^2.
Period Title: Overall Study
STARTED	42	41
COMPLETED	0	0
NOT COMPLETED	42	41

Baseline Characteristics

Arm/Group Title	NKTR-102	Irinotecan	Total
Arm/Group Description	NKTR-102 NKTR-102: IV every 3 weeks	IV every 3 weeks irinotecan: IV every 3 weeks	Total of all reporting groups
Overall Participants	42	41	83
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	30 71.4%	30 73.2%	60 72.3%
>=65 years	12 28.6%	11 26.8%	23 27.7%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.5 (10.65)	57.8 (11.4)	58.2 (10.97)
Sex: Female, Male (Count of Participants)
Female	18 42.9%	16 39%	34 41%
Male	24 57.1%	25 61%	49 59%

Outcome Measures

1. Primary Outcome

Title	Kaplan-Meier Estimate of PFS by Central Radiological Review: ITT Population
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	NKTR-102	Irinotecan
Arm/Group Description	NKTR-102 IV every 3 weeks	irinotecan IV every 3 weeks
Measure Participants	42	41
Median (95% Confidence Interval) [months]	4.0	2.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NKTR-102, Irinotecan
	Comments
	Type of Statistical Test	Other
	Comments	Hazard Ratio and 95% CI from univariate Cox regression model
Statistical Test of Hypothesis	p-Value	= 0.07
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.645
	Confidence Interval	(2-Sided) 95%; 0.4 to 1.041
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Kaplan-Meier Estimate of OS: ITT Population
Description	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.
Time Frame	From randomization to death, loss to follow-up, withdrawal of consent for further follow-up for survival, or end of study, approximately 42 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	NKTR-102	Irinotecan
Arm/Group Description	NKTR-102 IV every 3 weeks	irinotecan IV every 3 weeks
Measure Participants	42	41
Median (95% Confidence Interval) [months]	9.6	8.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NKTR-102, Irinotecan
	Comments
	Type of Statistical Test	Other
	Comments	Hazard ratio and 95% CI from univariate Cox regression model.
Statistical Test of Hypothesis	p-Value	= 0.706
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.91
	Confidence Interval	(2-Sided) 95%; 0.557 to 1.486
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	ORR by Central Radiological Review: ITT Population
Description	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.
Time Frame	From randomization of the first subject until documented disease progression, start of new therapy for cancer, death, or end of study approximately 42 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	NKTR-102	Irinotecan
Arm/Group Description	NKTR-102 IV every 3 weeks	irinotecan IV every 3 weeks
Measure Participants	42	41
Median (95% Confidence Interval) [percentage of patients]	9.8	5.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NKTR-102, Irinotecan
	Comments
	Type of Statistical Test	Other
	Comments	ORR 95% CI based on Exact (Clopper-Pearson) confidence limits. Odds ratio 95% CI based on asymptotic confidence limits.
Statistical Test of Hypothesis	p-Value	= 0.676
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.054
	Confidence Interval	(2-Sided) 95%; 0.355 to 11.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	DoR by Central Radiological Review: ITT Population
Description	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
Time Frame	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	NKTR-102	Irinotecan
Arm/Group Description	NKTR-102 IV every 3 weeks	irinotecan IV every 3 weeks
Measure Participants	42	41
Median (95% Confidence Interval) [months]	7.9	1.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NKTR-102, Irinotecan
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	= 0.018
	Comments
	Method	Log Rank
	Comments

5. Secondary Outcome

Title	Percentage of Participants (≥2%) With Treatment-Emergent Adverse Events NCI-CTCAE Grade 3 or Higher
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	NKTR-102	Irinotecan
Arm/Group Description	NKTR-102 IV every 3 weeks	irinotecan IV every 3 weeks
Measure Participants	42	41
Percentage of participants with ≥1 TEAE	61.9 147.4%	63.9 155.9%
Percentage of participants with Diarrhea	21.4 51%	19.5 47.6%
Percentage of participants with Neutropenia	7.1 16.9%	14.6 35.6%
Percentage of participants with Abdominal Pain	14.3 34%	4.9 12%
Percentage of participants with Dehydration	9.5 22.6%	9.8 23.9%
Percentage of participants with Vomiting	11.9 28.3%	7.3 17.8%
Percentage of participants with Nausea	14.3 34%	2.4 5.9%
Percentage of participants with Hypokalemia	7.1 16.9%	7.3 17.8%
Percentage of participants with Fatigue	9.5 22.6%	2.4 5.9%
Percentage of participants with Intestinal Obstruction	2.4 5.7%	9.8 23.9%
Percentage of participants with Leukopenia	7.1 16.9%	4.9 12%
Percentage of participants with Febrile Neutropenia	2.4 5.7%	7.3 17.8%
Percentage of participants with Alopecia	2.4 5.7%	4.9 12%
Percentage of participants with Disease Progression	4.8 11.4%	2.4 5.9%
Percentage of participants with Hyponatremia	2.4 5.7%	4.9 12%
Percentage of participants with Acute Prerenal Failure	2.4 5.7%	2.4 5.9%
Percentage of participants with Asthenia	2.4 5.7%	2.4 5.9%
Percentage of participants with Hyperbilirubinemia	2.4 5.7%	2.4 5.9%
Percentage of participants with Performance Status Decreased	4.8 11.4%	0 0%
Percentage of participants with Sepsis	0 0%	4.9 12%

6. Secondary Outcome

Title	PK Parameters of NKTR-102 or Irinotecan and Respective Metabolites
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

There are no data available for this outcome, due to the very small number of PK samples that were collected from these patients.

Arm/Group Title	NKTR-102	Irinotecan
Arm/Group Description	NKTR-102 IV every 3 weeks	irinotecan IV every 3 weeks
Measure Participants	0	0

Adverse Events

Time Frame	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
Arm/Group Title	NKTR-102		Irinotecan
Arm/Group Description	NKTR-102 IV every 3 weeks		irinotecan IV every 3 weeks
All Cause Mortality
	NKTR-102		Irinotecan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	32/42 (76.2%)		30/41 (73.2%)
Serious Adverse Events
	NKTR-102		Irinotecan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/42 (45.2%)		24/41 (58.5%)
Blood and lymphatic system disorders
Neutropenia	0/42 (0%)	0	3/41 (7.3%)	3
Febrile neutropenia	1/42 (2.4%)	1	1/41 (2.4%)	1
Leukopenia	0/42 (0%)	0	2/41 (4.9%)	2
Anaemia	0/42 (0%)	0	1/41 (2.4%)	1
Thrombocytopenia	0/42 (0%)	0	1/41 (2.4%)	1
Gastrointestinal disorders
Diarrhoea	4/42 (9.5%)	5	7/41 (17.1%)	8
Intestinal obstruction	1/42 (2.4%)	1	4/41 (9.8%)	6
Vomiting	2/42 (4.8%)	2	2/41 (4.9%)	2
Abdominal pain	2/42 (4.8%)	2	1/41 (2.4%)	1
Nausea	2/42 (4.8%)	3	1/41 (2.4%)	1
Anorectal discomfort	0/42 (0%)	0	1/41 (2.4%)	1
Ascites	0/42 (0%)	0	1/41 (2.4%)	1
Colitis	0/42 (0%)	0	1/41 (2.4%)	1
Gastrointestinal haemorrhage	0/42 (0%)	0	1/41 (2.4%)	1
Faecaloma	1/42 (2.4%)	1	0/41 (0%)	0
Ileus	0/42 (0%)	0	1/41 (2.4%)	1
Large intestinal obstruction	1/42 (2.4%)	1	0/41 (0%)	0
Rectal haemorrhage	1/42 (2.4%)	1	0/41 (0%)	0
Small intestinal haemorrhage	0/42 (0%)	0	1/41 (2.4%)	1
Small intestinal obstruction	0/42 (0%)	0	1/41 (2.4%)	1
General disorders
Disease progression	2/42 (4.8%)	2	1/41 (2.4%)	1
Asthenia	1/42 (2.4%)	1	0/41 (0%)	0
Chest pain	1/42 (2.4%)	1	0/41 (0%)	0
Fatigue	1/42 (2.4%)	1	0/41 (0%)	0
Performance status decreased	1/42 (2.4%)	1	0/41 (0%)	0
Hepatobiliary disorders
Hyperbilirubinaemia	1/42 (2.4%)	1	1/41 (2.4%)	1
Cholecystitis	0/42 (0%)	0	1/41 (2.4%)	1
Infections and infestations
Sepsis	0/42 (0%)	0	3/41 (7.3%)	3
Diarrhoea Infectious	0/42 (0%)	0	1/41 (2.4%)	1
Escherichia infection	1/42 (2.4%)	4	0/41 (0%)	0
Orchitis	0/42 (0%)	0	1/41 (2.4%)	1
Injury, poisoning and procedural complications
Therapeutic agent toxicity	0/42 (0%)	0	1/41 (2.4%)	1
Metabolism and nutrition disorders
Dehydration	3/42 (7.1%)	3	3/41 (7.3%)	3
Hypokalaemia	1/42 (2.4%)	1	1/41 (2.4%)	1
Hyponatraemia	0/42 (0%)	0	1/41 (2.4%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour ulceration	0/42 (0%)	0	1/41 (2.4%)	1
Nervous system disorders
Dizziness	0/42 (0%)	0	1/41 (2.4%)	1
Somnolence	1/42 (2.4%)	1	0/41 (0%)	0
Transient ischaemic attack	1/42 (2.4%)	1	0/41 (0%)	0
Renal and urinary disorders
Acute prerenal failure	1/42 (2.4%)	1	1/41 (2.4%)	1
Renal failure acute	1/42 (2.4%)	1	0/41 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	0/42 (0%)	0	1/41 (2.4%)	1
Dyspnoea	1/42 (2.4%)	1	0/41 (0%)	0
Hypoxia	1/42 (2.4%)		0/41 (0%)
Pulmonary embolism	1/42 (2.4%)	1	0/41 (0%)	0
Vascular disorders
Deep vein thrombosis	0/42 (0%)	0	1/41 (2.4%)	1
Other (Not Including Serious) Adverse Events
	NKTR-102		Irinotecan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	42/42 (100%)		38/41 (92.7%)
Blood and lymphatic system disorders
Anaemia	6/42 (14.3%)	7	6/41 (14.6%)	7
Leukopenia	5/42 (11.9%)	7	1/41 (2.4%)	1
Neutropenia	7/42 (16.7%)	14	5/41 (12.2%)	8
Thrombocytopenia	4/42 (9.5%)	5	4/41 (9.8%)	4
Eye disorders
Vision blurred	5/42 (11.9%)	5	1/41 (2.4%)	1
Gastrointestinal disorders
Diarrhoea	26/42 (61.9%)	62	28/41 (68.3%)	66
Nausea	23/42 (54.8%)	41	24/41 (58.5%)	45
Vomiting	17/42 (40.5%)	27	20/41 (48.8%)	33
Abdominal pain	17/42 (40.5%)	25	13/41 (31.7%)	21
Constipation	12/42 (28.6%)	18	10/41 (24.4%)	16
Abdominal pain upper	5/42 (11.9%)	5	4/41 (9.8%)	5
Dyspepsia	3/42 (7.1%)	3	4/41 (9.8%)	4
Abdominal distension	1/42 (2.4%)	1	5/41 (12.2%)	5
Proctalgia	2/42 (4.8%)	2	3/41 (7.3%)	3
General disorders
Fatigue	20/42 (47.6%)	25	18/41 (43.9%)	34
Pyrexia	4/42 (9.5%)	8	7/41 (17.1%)	7
Asthenia	6/42 (14.3%)	9	3/41 (7.3%)	4
Oedema peripheral	1/42 (2.4%)	1	4/41 (9.8%)	4
Investigations
Haemoglobin decreased	2/42 (4.8%)	7	6/41 (14.6%)	8
Weight decreased	13/42 (31%)	14	6/41 (14.6%)	6
Neutrophil count decreased	5/42 (11.9%)	8	2/41 (4.9%)	3
Metabolism and nutrition disorders
Anorexia	13/42 (31%)	15	10/41 (24.4%)	11
Dehydration	5/42 (11.9%)	5	5/41 (12.2%)	5
Hypokalaemia	9/42 (21.4%)	17	3/41 (7.3%)	9
Hyponatraemia	5/42 (11.9%)	5	2/41 (4.9%)	4
Musculoskeletal and connective tissue disorders
Back pain	3/42 (7.1%)	3	3/41 (7.3%)	4
Pain in extremity	3/42 (7.1%)	3	3/41 (7.3%)	3
Nervous system disorders
Lethargy	3/42 (7.1%)	10	5/41 (12.2%)	19
Headache	5/42 (11.9%)	5	1/41 (2.4%)	1
Dizziness	7/42 (16.7%)	7	6/41 (14.6%)	10
Psychiatric disorders
Anxiety	5/42 (11.9%)	7	0/41 (0%)	0
Insomnia	3/42 (7.1%)	3	2/41 (4.9%)	2
Respiratory, thoracic and mediastinal disorders
Cough	2/42 (4.8%)	2	3/41 (7.3%)	4
Dyspnoea	3/42 (7.1%)	3	2/41 (4.9%)	2
Skin and subcutaneous tissue disorders
Alopecia	7/42 (16.7%)	8	24/41 (58.5%)	27

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There are restrictions to the PI's rights to discuss or publish trial results.