MACS0460: RAPTOR: RAD001 as Monotherapy in the Treatment of Advanced Papillary Renal Cell Tumors Program in Europe

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00688753
• Collaborator: (none)
• Enrollment: 92
• Locations: 19
• Arm: 1
• Duration (Months): 63
• Patients Per Site: 4.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

To evaluate the preliminary efficacy and safety of RAD001 as monotherapy for first-line treatment of patients with metastatic papillary carcinoma of the kidney.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma; Renal Cell; Non Clear Cell Renal Carcinoma; Papillary Cell Renal Carcinoma; Adenocarcinoma	Drug: RAD001	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 92 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Single Arm, Multicenter Phase II Trial of RAD001 as Monotherapy in the Treatment of Advanced Papillary Renal Cell Cancer
• Study Start Date: Jul 1, 2009
• Actual Primary Completion Date: Oct 1, 2014
• Actual Study Completion Date: Oct 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: RAD001 two 5 mg tablets of everolimus orally, once daily	Drug: RAD001

Outcome Measures

Primary Outcome Measures

1. To Evaluate Efficacy of RAD001 as Monotherapy for the Treatment of Papillary Renal Cancer. Efficacy is Defined as the Percentage of Patients Progression-free at 6 Months. [6 mos]

   PFSR at 6 months based on central review

Secondary Outcome Measures

1. Disease Control Rate (SD + PR + CR) [6 mos]

   DCR was defined as the proportion of patients with a best overall response of CR, PR or SD and ORR as the percentage of patients with CR or PR

2. Objective Response Rate [End of trial]

   ORR is defined as the proportion of patients with tumor size reduction of a predefined amount and for a minimum time period. Response duration usually is measured from the time of initial response until documented tumor progression

3. Duration of Response [End of trial]

   The DOR analysis applied only to patients whose overall response was CR or PR and was defined as the time from onset of response (CR/PR) to progression or death from any cause.

4. Median Progression Free Survival [End of trial]

   PFS was defined as the time from first study drug administration to objective tumor progression or death from any cause.

5. Incidence of Adverse Events, Serious Adverse Events, and Death. [End of trial]

Eligibility Criteria

Criteria

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

Inclusion criteria:

1. ≥ 18 years old.

2. Patients with metastatic papillary renal cell carcinoma, type I or II.

3. Patients with at least one measurable lesion.

4. Patients with an ECOG Performance Status ≤1.

5. Adequate bone marrow function.

6. Adequate liver function.

7. Adequate renal function.

8. Adequate lipid profile.

Exclusion criteria:

1. Patients who had radiation therapy within 28 days prior to start of study.

2. Patients who have received prior systemic treatment for their metastatic RCC.

3. Patients who received prior therapy with VEGF pathway inhibitor.

4. Patients who have previously received systemic mTOR inhibitors.

5. Patients with a known hypersensitivity everolimus or other rapamycins or to its excipients.

6. Patients with uncontrolled central nervous system (CNS) metastases.

7. Patients receiving chronic systemic treatment with corticosteroids or another immunosuppressive agent.

8. Patients with a known history of HIV seropositivity.

9. Patients with autoimmune hepatitis.

10. Patients with an active, bleeding diathesis.

11. Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study.

12. Patients who have a history of another primary malignancy and off treatment ≤ 3 years, with the exception of non-melanoma skin cancer and carcinoma in situ of the uterine cervix.

13. Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods.

14. Patients who are using other investigational agents or who had received investigational drugs ≤ 4 weeks prior to study treatment start.

15. Patients unwilling to or unable to comply with the protocol.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Brussels		Belgium	BE-B-1200
2	Novartis Investigative Site	Gent		Belgium	9000
3	Novartis Investigative Site	Bordeaux Cedex		France	33075
4	Novartis Investigative Site	Lyon Cedex		France	69373
5	Novartis Investigative Site	Marseille		France	13273
6	Novartis Investigative Site	Paris		France	75015
7	Novartis Investigative Site	Villejuif Cedex		France	94805
8	Novartis Investigative Site	Berlin		Germany	10098
9	Novartis Investigative Site	Hannover		Germany	30625
10	Novartis Investigative Site	Muenster		Germany	48149
11	Novartis Investigative Site	Arezzo	AR	Italy	52100
12	Novartis Investigative Site	Cremona	CR	Italy	26100
13	Novartis Investigative Site	Pavia	PV	Italy	27100
14	Novartis Investigative Site	Napoli		Italy	80132
15	Novartis Investigative Site	Otwock		Poland	05-400
16	Novartis Investigative Site	Barcelona	Catalunya	Spain	08003
17	Novartis Investigative Site	Barcelona	Cataluña	Spain	08907
18	Novartis Investigative Site	Valencia	Comunidad Valenciana	Spain	46009
19	Novartis Investigative Site	Barcelona		Spain	08041

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00688753
• Other Study ID Numbers: CRAD001LFR08; 2008-006181-28
• First Posted: Jun 3, 2008
• Last Update Posted: Sep 2, 2016
• Last Verified: Jul 1, 2016

• Keywords provided by Novartis Pharmaceuticals: renal cell carcinoma; non clear cell carcinoma; papillary cell renal carcinoma; adults; everolimus
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Renal Cell; Kidney Neoplasms; Everolimus

Study Results

Participant Flow

Arm/Group Title	RAD001
Arm/Group Description	two 5 mg tablets orally, once daily at the same time every day immediately after a meal
Period Title: Overall Study
STARTED	92
COMPLETED	0
NOT COMPLETED	92

Baseline Characteristics

Arm/Group Title	RAD001 10 mg
Arm/Group Description	two 5 mg tablets of everolimus orally, once daily
Overall Participants	92
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	76 82.6%
>=65 years	16 17.4%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.9 (14.9)
Sex: Female, Male (Count of Participants)
Female	20 21.7%
Male	72 78.3%

Outcome Measures

1. Primary Outcome

Title	To Evaluate Efficacy of RAD001 as Monotherapy for the Treatment of Papillary Renal Cancer. Efficacy is Defined as the Percentage of Patients Progression-free at 6 Months.
Description	PFSR at 6 months based on central review
Time Frame	6 mos

Outcome Measure Data

Analysis Population Description

PP, PPFF, ITT

Arm/Group Title	RAD001
Arm/Group Description	10 mg/day
Measure Participants	92
(PPFF Set, N=44)	34.1 37.1%
(PPSet, N=66)	33.3 36.2%
(ITT Set, N=86)	32.6 35.4%

2. Secondary Outcome

Title	Disease Control Rate (SD + PR + CR)
Description	DCR was defined as the proportion of patients with a best overall response of CR, PR or SD and ORR as the percentage of patients with CR or PR
Time Frame	6 mos

Outcome Measure Data

Analysis Population Description

PP,ITT

Arm/Group Title	RAD001
Arm/Group Description	10 mg/day
Measure Participants	92
PP set	65.2 70.9%
ITT set	65.1 70.8%

3. Secondary Outcome

Title	Objective Response Rate
Description	ORR is defined as the proportion of patients with tumor size reduction of a predefined amount and for a minimum time period. Response duration usually is measured from the time of initial response until documented tumor progression
Time Frame	End of trial

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RAD001
Arm/Group Description	10 mg/day
Measure Participants	92
PP Set	1.5 1.6%
ITT Set	1.2 1.3%

4. Secondary Outcome

Title	Duration of Response
Description	The DOR analysis applied only to patients whose overall response was CR or PR and was defined as the time from onset of response (CR/PR) to progression or death from any cause.
Time Frame	End of trial

Outcome Measure Data

Analysis Population Description

In the final analysis, for central review, the DOR could not be calculated as only 1 patient in the PP and ITT sets met the criteria

Arm/Group Title	RAD001
Arm/Group Description	10 mg/day
Measure Participants	92
local review PP set	169
local review ITT set	226

5. Secondary Outcome

Title	Median Progression Free Survival
Description	PFS was defined as the time from first study drug administration to objective tumor progression or death from any cause.
Time Frame	End of trial

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RAD001
Arm/Group Description	10 mg/day
Measure Participants	92
PP set	118
ITT set	113

6. Secondary Outcome

Title	Incidence of Adverse Events, Serious Adverse Events, and Death.
Time Frame	End of trial

Outcome Measure Data

Analysis Population Description

Safety Set

Arm/Group Title	RAD001
Arm/Group Description	10 mg/day
Measure Participants	92
Patients with any AE	100 108.7%
AE with suspected relation to study drug	97.83 106.3%
AE leading to dose adjustment or interruption	53.26 57.9%
AE leading to permanent discontinuation	27.17 29.5%
AE requiring concomitant medication	90.22 98.1%
Patients with serious adverse event (SAE)	46.74 50.8%
SAE suspected relation to study drug	23.91 26%
SAE leading to permanent discontinuation	10.87 11.8%
Patients died	10.87 11.8%

Adverse Events

Arm/Group Title	All Patients
Arm/Group Description	two 5 mg tablets orally, once daily at the same time every day immediately after a meal
All Cause Mortality
	All Patients
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	All Patients
	Affected / at Risk (%)	# Events
Total	43/92 (46.7%)
Blood and lymphatic system disorders
Anaemia	4/92 (4.3%)
Cardiac disorders
Atrial fibrillation	1/92 (1.1%)
Atrial flutter	1/92 (1.1%)
Cardiac arrest	1/92 (1.1%)
Cor pulmonale	1/92 (1.1%)
Tricuspid valve incompetence	1/92 (1.1%)
Gastrointestinal disorders
Abdominal pain	2/92 (2.2%)
Ascites	2/92 (2.2%)
Colitis	1/92 (1.1%)
Diarrhoea	1/92 (1.1%)
Ileus	1/92 (1.1%)
Large intestine polyp	1/92 (1.1%)
Oesophagitis	1/92 (1.1%)
Subileus	1/92 (1.1%)
Vomiting	1/92 (1.1%)
General disorders
Asthenia	4/92 (4.3%)
Chest pain	1/92 (1.1%)
Condition aggravated	2/92 (2.2%)
General physical health deterioration	2/92 (2.2%)
Mucosal inflammation	1/92 (1.1%)
Multi-organ failure	1/92 (1.1%)
Oedema peripheral	1/92 (1.1%)
Pyrexia	4/92 (4.3%)
Hepatobiliary disorders
Cholestasis	1/92 (1.1%)
Infections and infestations
Anal infection	1/92 (1.1%)
Bacteraemia	1/92 (1.1%)
Cellulitis	1/92 (1.1%)
Erysipelas	1/92 (1.1%)
Gastrointestinal infection	1/92 (1.1%)
Herpes zoster	1/92 (1.1%)
Pneumonia	2/92 (2.2%)
Pneumonia bacterial	1/92 (1.1%)
Postoperative abscess	1/92 (1.1%)
Respiratory tract infection	1/92 (1.1%)
Upper respiratory tract infection	1/92 (1.1%)
Injury, poisoning and procedural complications
Lumbar vertebral fracture	1/92 (1.1%)
Investigations
Blood creatinine increased	1/92 (1.1%)
Metabolism and nutrition disorders
Dehydration	2/92 (2.2%)
Fluid overload	1/92 (1.1%)
Hyperglycaemia	1/92 (1.1%)
Hyponatraemia	1/92 (1.1%)
Musculoskeletal and connective tissue disorders
Back pain	1/92 (1.1%)
Bone pain	1/92 (1.1%)
Fistula	1/92 (1.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm progression	4/92 (4.3%)
Nervous system disorders
Aphasia	1/92 (1.1%)
Hemiparesis	1/92 (1.1%)
Spinal cord compression	1/92 (1.1%)
Tremor	1/92 (1.1%)
Psychiatric disorders
Depression	1/92 (1.1%)
Hallucination	1/92 (1.1%)
Renal and urinary disorders
Renal failure	3/92 (3.3%)
Renal failure acute	4/92 (4.3%)
Reproductive system and breast disorders
Vaginal haemorrhage	1/92 (1.1%)
Respiratory, thoracic and mediastinal disorders
Cough	1/92 (1.1%)
Dyspnoea	3/92 (3.3%)
Dyspnoea exertional	1/92 (1.1%)
Epistaxis	1/92 (1.1%)
Interstitial lung disease	1/92 (1.1%)
Lung disorder	1/92 (1.1%)
Nasal septum deviation	1/92 (1.1%)
Oropharyngeal pain	1/92 (1.1%)
Pleural effusion	4/92 (4.3%)
Pneumonitis	1/92 (1.1%)
Pulmonary arterial hypertension	1/92 (1.1%)
Pulmonary embolism	1/92 (1.1%)
Respiratory failure	1/92 (1.1%)
Skin and subcutaneous tissue disorders
Rash erythematous	2/92 (2.2%)
Vascular disorders
Deep vein thrombosis	2/92 (2.2%)
Hypertension	1/92 (1.1%)
Varicose vein	1/92 (1.1%)
Venous thrombosis	1/92 (1.1%)
Other (Not Including Serious) Adverse Events
	All Patients
	Affected / at Risk (%)	# Events
Total	90/92 (97.8%)
Blood and lymphatic system disorders
Anaemia	25/92 (27.2%)
Thrombocytopenia	10/92 (10.9%)
Cardiac disorders
Tachycardia	6/92 (6.5%)
Gastrointestinal disorders
Abdominal pain	23/92 (25%)
Aphthous stomatitis	11/92 (12%)
Ascites	5/92 (5.4%)
Constipation	15/92 (16.3%)
Diarrhoea	36/92 (39.1%)
Dry mouth	8/92 (8.7%)
Nausea	27/92 (29.3%)
Stomatitis	23/92 (25%)
Vomiting	16/92 (17.4%)
General disorders
Asthenia	39/92 (42.4%)
Chest pain	7/92 (7.6%)
Fatigue	30/92 (32.6%)
Mucosal inflammation	36/92 (39.1%)
Oedema peripheral	29/92 (31.5%)
Pain	7/92 (7.6%)
Pyrexia	25/92 (27.2%)
Infections and infestations
Bronchitis	5/92 (5.4%)
Rhinitis	9/92 (9.8%)
Urinary tract infection	6/92 (6.5%)
Investigations
Alanine aminotransferase increased	7/92 (7.6%)
Aspartate aminotransferase increased	6/92 (6.5%)
Blood creatinine increased	8/92 (8.7%)
Platelet count decreased	6/92 (6.5%)
Weight decreased	12/92 (13%)
Metabolism and nutrition disorders
Decreased appetite	36/92 (39.1%)
Hypercholesterolaemia	15/92 (16.3%)
Hyperglycaemia	12/92 (13%)
Hypertriglyceridaemia	10/92 (10.9%)
Hypocalcaemia	5/92 (5.4%)
Hypophosphataemia	8/92 (8.7%)
Musculoskeletal and connective tissue disorders
Arthralgia	11/92 (12%)
Back pain	16/92 (17.4%)
Musculoskeletal pain	5/92 (5.4%)
Myalgia	5/92 (5.4%)
Pain in extremity	10/92 (10.9%)
Nervous system disorders
Dysgeusia	23/92 (25%)
Headache	16/92 (17.4%)
Psychiatric disorders
Insomnia	9/92 (9.8%)
Respiratory, thoracic and mediastinal disorders
Cough	36/92 (39.1%)
Dyspnoea	29/92 (31.5%)
Epistaxis	26/92 (28.3%)
Pneumonitis	7/92 (7.6%)
Skin and subcutaneous tissue disorders
Acne	5/92 (5.4%)
Dry skin	12/92 (13%)
Nail disorder	13/92 (14.1%)
Palmar-plantar erythrodysaesthesia syndrome	5/92 (5.4%)
Pruritus	20/92 (21.7%)
Rash	53/92 (57.6%)
Vascular disorders
Hypertension	6/92 (6.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.