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Clinical Trial Results:
A Randomized Phase II Study of Afinitor (RAD001) vs. Sutent (Sunitinib) in Patients with Metastatic Non-Clear Cell Renal Cell Carcinoma (ASPEN)

Summary
EudraCT number	2010-019966-95
Trial protocol	GB
Global end of trial date	14 Jul 2015

Results information
Results version number	v1(current)
This version publication date	27 Jan 2022
First version publication date	27 Jan 2022
Other versions
Summary report(s)	Aspen Lancet Manuscript 2016 Aspen Lancet Manuscript Supplement

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

CRAD001L2402T

ISRCTN number

US NCT number

NCT01108445

WHO universal trial number (UTN)

Sponsor organisation name

Duke University

Sponsor organisation address

2424 Erwin Road, Hock Plaza, Durham, United States, 27705

Public contact

Monika Anand, Dr. Andrew Armstrong, 9196818838 9196818838, monika.anand@duke.edu

Scientific contact

Monika Anand, Dr. Andrew Armstrong, 9196818838 9196818838, monika.anand@duke.edu

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

31 Dec 2014

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

14 Jul 2015

Was the trial ended prematurely?

Main objective of the trial

The primary endpoint was a comparison of radiographic progression-free survival (rPFS) between the treatment arms following therapy initiation. Disease progression is defined by documentation of progressive disease according to RECIST 1.1 criteria, appearance of a new primary malignancy, or death (whichever occurs first), censored at the last tumor evaluation date.

Protection of trial subjects

All patients provided written informed consent under a form issued by an institutional review board. Regulatory oversight and nstitutional review board or ethics board approval in the USA, Canada, and the UK was maintained for this trial

Background therapy

Evidence for comparator

Actual start date of recruitment

23 Sep 2010

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

United Kingdom: 39

Country: Number of subjects enrolled

Canada: 5

Country: Number of subjects enrolled

United States: 64

Worldwide total number of subjects

108

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Between Sept 23, 2010, and Oct 28, 2013, 131 patients were assessed for eligibility and 109 patients were enrolled. 108 patients were evaluable. 51 patients were assigned sunitinib and 57 patients were assigned everolimus

Screening details

Number of subjects started

131 ^[1]

Number of subjects completed

108

Reason: Number of subjects

Screen Failures: 23

Notes
[1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: 131 patients consented to participate in the trial. These were considered to have started the pre-assignment period. 23 patients screen failed and were not assigned a study arm. 108 patients were enrolled to start treatment on trial.

Period 1 title

Baseline Characteristics (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Sunitinib

Arm description

Sunitinib malate was given orally at 50 mg once daily, for treatment cycles of 4 weeks on treatment and 2 weeks off treatment.

Arm type

Active comparator

Investigational medicinal product name

Sunitinib malate

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Sunitinib malate was given orally at 50 mg once daily, for treatment cycles of 4 weeks on treatment and 2 weeks off treatment.

Everolimus

Arm description

Everolimus was given orally at 10 mg once daily.

Arm type

Experimental

Investigational medicinal product name

Everolimus

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

10 mg tablet orally once daily

Number of subjects in period 1	Sunitinib	Everolimus
Started	51	57
Completed	41	44
Not completed	10	13
Consent withdrawn by subject	3	-
Adverse event, non-fatal	7	13

Baseline characteristics

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Reporting group title

Sunitinib

Reporting group description

Sunitinib malate was given orally at 50 mg once daily, for treatment cycles of 4 weeks on treatment and 2 weeks off treatment.

Reporting group title

Everolimus

Reporting group description

Everolimus was given orally at 10 mg once daily.

Reporting group values	Sunitinib	Everolimus	Total
Number of subjects	51	57	108
Age categorical
Units: Subjects
In utero			0
Preterm newborn infants (gestational age < 37 wks)			0
Newborns (0-27 days)			0
Infants and toddlers (28 days-23 months)			0
Children (2-11 years)			0
Adolescents (12-17 years)			0
Adults (18-64 years)			0
From 65-84 years			0
85 years and over			0
Age continuous
Units: years
median (full range (min-max))	59 (24 to 100)	64 (29 to 90)	-
Gender categorical
Units: Subjects
Female	14	13	27
Male	37	44	81
Ethnic Origin
Units: Subjects
White	42	52	94
Black	9	5	14
Unknown	0	0	0
MSKCC Risk Group
Units: Subjects
Low	15	14	29
Intermediate	32	32	64
High	4	11	15

End points

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Reporting group title

Sunitinib

Reporting group description

Sunitinib malate was given orally at 50 mg once daily, for treatment cycles of 4 weeks on treatment and 2 weeks off treatment.

Reporting group title

Everolimus

Reporting group description

Everolimus was given orally at 10 mg once daily.

Primary: Radiographic Progression Free Survival

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End point title

Radiographic Progression Free Survival

End point description

End point type

Primary

End point timeframe

Up to 24 months

End point values	Sunitinib	Everolimus
Number of subjects analysed	51	57
Units: Months
median (full range (min-max))	8.3 (5.8 to 11.4)	5.6 (5.5 to 6.0)

Primary outcome

Statistical analysis description

The null hypothesis was that PFS in patients treated with sunitinib(S) would be comparable to that of everolimus(E); the alternative hypothesis was that E would cause a 60% improvement in median PFS from 6∙0 months to 9∙6 months in S and E groups respectively, compared with S (HR 0∙625). Using a two-sided type I error rate of 0∙20, 90 PFS events would allow us to detect this difference with 83% power. PFS was tested using stratified log rank test, adjusting for stratification factors.

Comparison groups

Sunitinib v Everolimus

Number of subjects included in analysis

108

Analysis specification

Pre-specified

Analysis type

equivalence

Method

Parameter type

Hazard ratio (HR)

Point estimate

1.41

Confidence interval

level

80%

sides

2-sided

lower limit

1.03

upper limit

1.92

Secondary: Progression Free Survival at 12 Months

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End point title

Progression Free Survival at 12 Months

End point description

End point type

Secondary

End point timeframe

Up to 12 months

End point values	Sunitinib	Everolimus
Number of subjects analysed	51	57
Units: Percentage
number (not applicable)	37.7	17

No statistical analyses for this end point

Secondary: Progression Free Survival at 24 Months

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End point title

Progression Free Survival at 24 Months

End point description

End point type

Secondary

End point timeframe

Up to 24 months

End point values	Sunitinib	Everolimus
Number of subjects analysed	51	57
Units: Percentage
number (not applicable)	22.8	9.3

No statistical analyses for this end point

Secondary: Progression Free Survival at 6 Months

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End point title

Progression Free Survival at 6 Months

End point description

End point type

Secondary

End point timeframe

Up to 6 months

End point values	Sunitinib	Everolimus
Number of subjects analysed	51	57
Units: Percentage
number (not applicable)	55	40.3

No statistical analyses for this end point

Secondary: Overall Survival

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End point title

Overall Survival

End point description

End point type

Secondary

End point timeframe

Up to 36 months post randomization

End point values	Sunitinib	Everolimus
Number of subjects analysed	51	57
Units: Months
median (confidence interval 95%)	31.5 (14.8 to 45.43)	13.2 (9.7 to 37.9)

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

AEs were assessed up to 28 days post last day of dose given to the last patient on treatment.

Assessment type

Non-systematic

Dictionary name

NCI CTC

Dictionary version

Reporting group title

Sunitinib

Reporting group description

Sunitinib malate was given orally at 50 mg once daily, for treatment cycles of 4 weeks on treatment and 2 weeks off treatment.

Reporting group title

Everolimus

Reporting group description

Everolimus was given orally at 10 mg once daily.

Serious adverse events	Sunitinib	Everolimus
Total subjects affected by serious adverse events
subjects affected / exposed	21 / 51 (41.18%)	15 / 57 (26.32%)
number of deaths (all causes)	1	1
number of deaths resulting from adverse events	0	0
Injury, poisoning and procedural complications
HEMATOMA - SUBDURAL
subjects affected / exposed	1 / 51 (1.96%)	0 / 57 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular disorders
HYPERTENSION
subjects affected / exposed	2 / 51 (3.92%)	0 / 57 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
DVT RT LWR LEG
subjects affected / exposed	1 / 51 (1.96%)	0 / 57 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
General disorders and administration site conditions
MUCOSITIS
subjects affected / exposed	0 / 51 (0.00%)	1 / 57 (1.75%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal disorders
NAUSEA
subjects affected / exposed	1 / 51 (1.96%)	0 / 57 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
PANCREATITIS
subjects affected / exposed	1 / 51 (1.96%)	0 / 57 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
VOMITING
subjects affected / exposed	1 / 51 (1.96%)	0 / 57 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
HYPEREMESIS
subjects affected / exposed	1 / 51 (1.96%)	0 / 57 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Diarrhoea
subjects affected / exposed	0 / 51 (0.00%)	1 / 57 (1.75%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
EPISTAXIS
subjects affected / exposed	2 / 51 (3.92%)	0 / 57 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
PAIN - LEFT PLEURETIC CHEST PAIN
subjects affected / exposed	1 / 51 (1.96%)	0 / 57 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
SHORTNESS OF BREATH
subjects affected / exposed	1 / 51 (1.96%)	0 / 57 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
PULMONARY EMBOLISM
subjects affected / exposed	1 / 51 (1.96%)	0 / 57 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
PNEUMONITIS
subjects affected / exposed	0 / 51 (0.00%)	5 / 57 (8.77%)
occurrences causally related to treatment / all	0 / 0	4 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
THROMBOSIS / EMBOLISM
subjects affected / exposed	0 / 51 (0.00%)	1 / 57 (1.75%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
WORSENED DYSPNEA
subjects affected / exposed	1 / 51 (1.96%)	1 / 57 (1.75%)
occurrences causally related to treatment / all	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 1	0 / 0
Hepatobiliary disorders
CHOLECYSTITIS
subjects affected / exposed	1 / 51 (1.96%)	0 / 57 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Psychiatric disorders
CONFUSION
subjects affected / exposed	1 / 51 (1.96%)	0 / 57 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
ALTERED MENTAL STATUS
subjects affected / exposed	1 / 51 (1.96%)	0 / 57 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Renal and urinary disorders
ACUTE RENAL FAILURE
subjects affected / exposed	2 / 51 (3.92%)	0 / 57 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
RENAL IMPAIRMENT
subjects affected / exposed	0 / 51 (0.00%)	1 / 57 (1.75%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
LEFT LEG PAIN
subjects affected / exposed	1 / 51 (1.96%)	0 / 57 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
Urinary tract infection
subjects affected / exposed	1 / 51 (1.96%)	0 / 57 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
GASTROENTERITIS
subjects affected / exposed	0 / 51 (0.00%)	1 / 57 (1.75%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
LUNG INFECTION
subjects affected / exposed	0 / 51 (0.00%)	1 / 57 (1.75%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
NEPHROTOXICITY
subjects affected / exposed	0 / 51 (0.00%)	1 / 57 (1.75%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Metabolism and nutrition disorders
DEHYDRATION
subjects affected / exposed	0 / 51 (0.00%)	1 / 57 (1.75%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Sunitinib	Everolimus
Total subjects affected by non serious adverse events
subjects affected / exposed	51 / 51 (100.00%)	57 / 57 (100.00%)
Investigations
Thrombocytopenia
subjects affected / exposed	9 / 51 (17.65%)	4 / 57 (7.02%)
occurrences all number	15	5
Vascular disorders
Hypertension
subjects affected / exposed	19 / 51 (37.25%)	2 / 57 (3.51%)
occurrences all number	30	2
General disorders and administration site conditions
Fatigue
subjects affected / exposed	14 / 51 (27.45%)	18 / 57 (31.58%)
occurrences all number	28	25
Blood and lymphatic system disorders
Anemia
subjects affected / exposed	2 / 51 (3.92%)	13 / 57 (22.81%)
occurrences all number	2	22
Gastrointestinal disorders
Mucositis
subjects affected / exposed	3 / 51 (5.88%)	8 / 57 (14.04%)
occurrences all number	3	8
Nausea
subjects affected / exposed	10 / 51 (19.61%)	10 / 57 (17.54%)
occurrences all number	13	11
Respiratory, thoracic and mediastinal disorders
Dyspnea
subjects affected / exposed	3 / 51 (5.88%)	8 / 57 (14.04%)
occurrences all number	4	8
Infections and infestations
Stomatitis
subjects affected / exposed	3 / 51 (5.88%)	10 / 57 (17.54%)
occurrences all number	5	15
Metabolism and nutrition disorders
Anorexia
subjects affected / exposed	11 / 51 (21.57%)	4 / 57 (7.02%)
occurrences all number	14	4

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Were there any global substantial amendments to the protocol? No

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results:
A Randomized Phase II Study of Afinitor (RAD001) vs. Sutent (Sunitinib) in Patients with Metastatic Non-Clear Cell Renal Cell Carcinoma (ASPEN)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Radiographic Progression Free Survival

Primary: Radiographic Progression Free Survival

Secondary: Progression Free Survival at 12 Months

Secondary: Progression Free Survival at 12 Months

Secondary: Progression Free Survival at 24 Months

Secondary: Progression Free Survival at 24 Months

Secondary: Progression Free Survival at 6 Months

Secondary: Progression Free Survival at 6 Months

Secondary: Overall Survival

Secondary: Overall Survival

Adverse events

Adverse events

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Clinical trials

Clinical Trial Results: A Randomized Phase II Study of Afinitor (RAD001) vs. Sutent (Sunitinib) in Patients with Metastatic Non-Clear Cell Renal Cell Carcinoma (ASPEN)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Radiographic Progression Free Survival

Primary: Radiographic Progression Free Survival

Secondary: Progression Free Survival at 12 Months

Secondary: Progression Free Survival at 12 Months

Secondary: Progression Free Survival at 24 Months

Secondary: Progression Free Survival at 24 Months

Secondary: Progression Free Survival at 6 Months

Secondary: Progression Free Survival at 6 Months

Secondary: Overall Survival

Secondary: Overall Survival

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Randomized Phase II Study of Afinitor (RAD001) vs. Sutent (Sunitinib) in Patients with Metastatic Non-Clear Cell Renal Cell Carcinoma (ASPEN)