Trial Outcomes & Findings for Erlotinib and Sirolimus for the Treatment of Metastatic Renal Cell Carcinoma (NCT NCT00353301)

Last Updated: 2014-04-14

Results Overview

Time to progression was defined as the time from beginning of therapy until disease progression or death. For subjects who had not progressed at the time of statistical analysis, progression-free survival was censored at the date of their last tumor assessment. Kaplan-Meier method was used to estimate median progression-free survival. Progression was defined as radiographic progression according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria (year 2000 version), non-compliance in obtaining scans, unequivocal clinical progression or the initiation of another medication for the treatment of renal cell carcinoma.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

25 participants

Primary outcome timeframe

Physical exam assessments were performed every 4 weeks during the treatment phase. Survival follow-up information was collected every 4 months following the termination visit until death, loss to follow-up, or study termination up to 275 weeks.

Results posted on

2014-04-14

Participant Flow

This was a phase II, single-arm, single-institution trial. A total of 25 patients were enrolled between July 2006 and March 2008 from University of Colorado Cancer Center.

Patients with previous treatment with erlotinib, gefitinib, sirolimus, temsirolimus or everolimus, untreated central nervous system metastasis, renal failure requiring dialysis or significant liver dysfunction were excluded from the trial.

Participant milestones

Participant milestones
Measure	Erlotinib and Sirolimus Erlotinib (Tarceva) therapy was started at 150 mg by mouth daily from day 1 to be taken at least 1 hour before or 2 hours after a meal. Sirolimus was initiated on day 8 (D8) with a loading dose of 6mg by mouth, followed by a daily dose of 2mg by mouth, on the basis of the product prescribing information for low-to-moderate immunologic risk renal transplant patients.
Overall Study STARTED	25
Overall Study COMPLETED	25
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Erlotinib and Sirolimus for the Treatment of Metastatic Renal Cell Carcinoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Erlotinib and Sirolimus n=25 Participants Erlotinib (Tarceva) therapy was started at 150 mg by mouth daily from day 1 to be taken at least 1 hour before or 2 hours after a meal. Sirolimus was initiated on day 8 (D8) with a loading dose of 6mg by mouth, followed by a daily dose of 2mg by mouth, on the basis of the product prescribing information for low-to-moderate immunologic risk renal transplant patients.
Age, Continuous	60 years n=5 Participants
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	16 Participants n=5 Participants
Age, Categorical >=65 years	9 Participants n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants
Sex: Female, Male Male	20 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	25 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	21 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Region of Enrollment United States	25 Participants n=5 Participants

PRIMARY outcome

Timeframe: Physical exam assessments were performed every 4 weeks during the treatment phase. Survival follow-up information was collected every 4 months following the termination visit until death, loss to follow-up, or study termination up to 275 weeks.

Population: Per protocol analysis was used and 25 participants that were enrolled in the study were included in the analysis.

Outcome measures

Outcome measures
Measure	Erlotinib and Sirolimus n=25 Participants Erlotinib (Tarceva) therapy was started at 150 mg by mouth daily from day 1 to be taken at least 1 hour before or 2 hours after a meal. Sirolimus was initiated on day 8 (D8) with a loading dose of 6mg by mouth, followed by a daily dose of 2mg by mouth, on the basis of the product prescribing information for low-to-moderate immunologic risk renal transplant patients.
Progression-free Survival	12 Weeks Interval 5.9 to 18.1

SECONDARY outcome

Timeframe: Survival follow-up information was collected every 4 months following the termination visit until death, loss to follow-up, or study termination up to 275 weeks.

Population: Per protocol analysis was used and 25 participants that were enrolled in the study were included in the analysis.

For all subjects who had not died at the time of statistical analysis, duration of survival will was censored at the date of last contact. Kaplan-Meier methodology was used to estimate the magnitude of the treatment effect as described for progression-free survival.

Outcome measures

Outcome measures
Measure	Erlotinib and Sirolimus n=25 Participants Erlotinib (Tarceva) therapy was started at 150 mg by mouth daily from day 1 to be taken at least 1 hour before or 2 hours after a meal. Sirolimus was initiated on day 8 (D8) with a loading dose of 6mg by mouth, followed by a daily dose of 2mg by mouth, on the basis of the product prescribing information for low-to-moderate immunologic risk renal transplant patients.
Overall Survival	40 Weeks Interval 0.0 to 85.7

Adverse Events

Erlotinib and Sirolimus

Serious events: 2 serious events

Other events: 25 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Erlotinib and Sirolimus n=25 participants at risk Erlotinib (Tarceva) therapy was started at 150 mg by mouth daily from day 1 to be taken at least 1 hour before or 2 hours after a meal. Sirolimus was initiated on day 8 (D8) with a loading dose of 6mg by mouth, followed by a daily dose of 2mg by mouth, on the basis of the product prescribing information for low-to-moderate immunologic risk renal transplant patients.
Musculoskeletal and connective tissue disorders Chest pain	4.0% 1/25 • Adverse events were collected throughout the period of active therapy up to 4 weeks. Monitoring included patient interview, physical exam, routine laboratory tests (even in absence of symptoms) and appropriate work-up of any new symptoms or laboratorial abnormalities.
General disorders Hospitalization	4.0% 1/25 • Adverse events were collected throughout the period of active therapy up to 4 weeks. Monitoring included patient interview, physical exam, routine laboratory tests (even in absence of symptoms) and appropriate work-up of any new symptoms or laboratorial abnormalities.

Other adverse events

Other adverse events
Measure	Erlotinib and Sirolimus n=25 participants at risk Erlotinib (Tarceva) therapy was started at 150 mg by mouth daily from day 1 to be taken at least 1 hour before or 2 hours after a meal. Sirolimus was initiated on day 8 (D8) with a loading dose of 6mg by mouth, followed by a daily dose of 2mg by mouth, on the basis of the product prescribing information for low-to-moderate immunologic risk renal transplant patients.
Skin and subcutaneous tissue disorders Rash	96.0% 24/25 • Adverse events were collected throughout the period of active therapy up to 4 weeks. Monitoring included patient interview, physical exam, routine laboratory tests (even in absence of symptoms) and appropriate work-up of any new symptoms or laboratorial abnormalities.
Skin and subcutaneous tissue disorders Dry skin	32.0% 8/25 • Adverse events were collected throughout the period of active therapy up to 4 weeks. Monitoring included patient interview, physical exam, routine laboratory tests (even in absence of symptoms) and appropriate work-up of any new symptoms or laboratorial abnormalities.
Skin and subcutaneous tissue disorders Pruritis/pain	24.0% 6/25 • Adverse events were collected throughout the period of active therapy up to 4 weeks. Monitoring included patient interview, physical exam, routine laboratory tests (even in absence of symptoms) and appropriate work-up of any new symptoms or laboratorial abnormalities.
Blood and lymphatic system disorders Anaemia	56.0% 14/25 • Adverse events were collected throughout the period of active therapy up to 4 weeks. Monitoring included patient interview, physical exam, routine laboratory tests (even in absence of symptoms) and appropriate work-up of any new symptoms or laboratorial abnormalities.
Gastrointestinal disorders Diarrhoea	48.0% 12/25 • Adverse events were collected throughout the period of active therapy up to 4 weeks. Monitoring included patient interview, physical exam, routine laboratory tests (even in absence of symptoms) and appropriate work-up of any new symptoms or laboratorial abnormalities.
Gastrointestinal disorders Anorexia	36.0% 9/25 • Adverse events were collected throughout the period of active therapy up to 4 weeks. Monitoring included patient interview, physical exam, routine laboratory tests (even in absence of symptoms) and appropriate work-up of any new symptoms or laboratorial abnormalities.
Gastrointestinal disorders Mucositis	36.0% 9/25 • Adverse events were collected throughout the period of active therapy up to 4 weeks. Monitoring included patient interview, physical exam, routine laboratory tests (even in absence of symptoms) and appropriate work-up of any new symptoms or laboratorial abnormalities.
Gastrointestinal disorders Nausea	32.0% 8/25 • Adverse events were collected throughout the period of active therapy up to 4 weeks. Monitoring included patient interview, physical exam, routine laboratory tests (even in absence of symptoms) and appropriate work-up of any new symptoms or laboratorial abnormalities.
Blood and lymphatic system disorders Hypoalbuminaemia	48.0% 12/25 • Adverse events were collected throughout the period of active therapy up to 4 weeks. Monitoring included patient interview, physical exam, routine laboratory tests (even in absence of symptoms) and appropriate work-up of any new symptoms or laboratorial abnormalities.
Blood and lymphatic system disorders Elevated creatinine	40.0% 10/25 • Adverse events were collected throughout the period of active therapy up to 4 weeks. Monitoring included patient interview, physical exam, routine laboratory tests (even in absence of symptoms) and appropriate work-up of any new symptoms or laboratorial abnormalities.
Blood and lymphatic system disorders Hypertriglyceridaemia	36.0% 9/25 • Adverse events were collected throughout the period of active therapy up to 4 weeks. Monitoring included patient interview, physical exam, routine laboratory tests (even in absence of symptoms) and appropriate work-up of any new symptoms or laboratorial abnormalities.
Blood and lymphatic system disorders Hypophosphataemia	28.0% 7/25 • Adverse events were collected throughout the period of active therapy up to 4 weeks. Monitoring included patient interview, physical exam, routine laboratory tests (even in absence of symptoms) and appropriate work-up of any new symptoms or laboratorial abnormalities.
General disorders Fatigue	44.0% 11/25 • Adverse events were collected throughout the period of active therapy up to 4 weeks. Monitoring included patient interview, physical exam, routine laboratory tests (even in absence of symptoms) and appropriate work-up of any new symptoms or laboratorial abnormalities.
General disorders Pain	28.0% 7/25 • Adverse events were collected throughout the period of active therapy up to 4 weeks. Monitoring included patient interview, physical exam, routine laboratory tests (even in absence of symptoms) and appropriate work-up of any new symptoms or laboratorial abnormalities.
General disorders Chills/cold intolerance	24.0% 6/25 • Adverse events were collected throughout the period of active therapy up to 4 weeks. Monitoring included patient interview, physical exam, routine laboratory tests (even in absence of symptoms) and appropriate work-up of any new symptoms or laboratorial abnormalities.
General disorders Weight loss	24.0% 6/25 • Adverse events were collected throughout the period of active therapy up to 4 weeks. Monitoring included patient interview, physical exam, routine laboratory tests (even in absence of symptoms) and appropriate work-up of any new symptoms or laboratorial abnormalities.
Respiratory, thoracic and mediastinal disorders Cough	28.0% 7/25 • Adverse events were collected throughout the period of active therapy up to 4 weeks. Monitoring included patient interview, physical exam, routine laboratory tests (even in absence of symptoms) and appropriate work-up of any new symptoms or laboratorial abnormalities.
Respiratory, thoracic and mediastinal disorders Rhinitis	28.0% 7/25 • Adverse events were collected throughout the period of active therapy up to 4 weeks. Monitoring included patient interview, physical exam, routine laboratory tests (even in absence of symptoms) and appropriate work-up of any new symptoms or laboratorial abnormalities.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	4.0% 1/25 • Adverse events were collected throughout the period of active therapy up to 4 weeks. Monitoring included patient interview, physical exam, routine laboratory tests (even in absence of symptoms) and appropriate work-up of any new symptoms or laboratorial abnormalities.
Cardiac disorders Decreased left ventricular ejection fraction	4.0% 1/25 • Adverse events were collected throughout the period of active therapy up to 4 weeks. Monitoring included patient interview, physical exam, routine laboratory tests (even in absence of symptoms) and appropriate work-up of any new symptoms or laboratorial abnormalities.
Cardiac disorders Myocardial infarction	4.0% 1/25 • Adverse events were collected throughout the period of active therapy up to 4 weeks. Monitoring included patient interview, physical exam, routine laboratory tests (even in absence of symptoms) and appropriate work-up of any new symptoms or laboratorial abnormalities.
Cardiac disorders Tachycardia	4.0% 1/25 • Adverse events were collected throughout the period of active therapy up to 4 weeks. Monitoring included patient interview, physical exam, routine laboratory tests (even in absence of symptoms) and appropriate work-up of any new symptoms or laboratorial abnormalities.
Cardiac disorders Anuria	4.0% 1/25 • Adverse events were collected throughout the period of active therapy up to 4 weeks. Monitoring included patient interview, physical exam, routine laboratory tests (even in absence of symptoms) and appropriate work-up of any new symptoms or laboratorial abnormalities.
Respiratory, thoracic and mediastinal disorders Epistaxis	24.0% 6/25 • Adverse events were collected throughout the period of active therapy up to 4 weeks. Monitoring included patient interview, physical exam, routine laboratory tests (even in absence of symptoms) and appropriate work-up of any new symptoms or laboratorial abnormalities.
Respiratory, thoracic and mediastinal disorders Haemorrhage/bleeding other	24.0% 6/25 • Adverse events were collected throughout the period of active therapy up to 4 weeks. Monitoring included patient interview, physical exam, routine laboratory tests (even in absence of symptoms) and appropriate work-up of any new symptoms or laboratorial abnormalities.

Additional Information

Dr. Thomas Flaig

University of Colorado, Denver

Phone: (720) 848-0655

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place