Trial Outcomes & Findings for Trastuzumab and RAD001 in Patients With Human Epidermal Growth Receptor 2 (HER-2) Overexpressing Breast Cancer (NCT NCT00317720)

Last Updated: 2025-04-30

Results Overview

In Phase I, two dose levels of RAD001 were studied: 10 mg (dose level 1) and 5 mg (dose level -1) where each dose was evaluated after cycle 1. At MDACC, the Continual Reassessment Method (CRM) for determining Maximum Tolerated Dose (MTD) was applied to the two predefined RAD001 dose levels; and at DFCI/BIDMC, a 3 x 3 study design was utilized. Optimal dose defined as the dose most closely associated with a toxicity rate of 0.20, and toxicity defined as any grade 3 or 4 toxicity (based on Common Terminology Criteria (CTC) version 3.0 except fatigue. Participants underwent clinical evaluation every 3 weeks (one cycle) and radiologic evaluations every 6 weeks. After the second cycle, participants underwent a radiologic evaluation using the same imaging technique used at initial evaluation (ie, computed tomography or magnetic resonance imaging).

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

40 participants

Primary outcome timeframe

Following two 3 week cycles of therapy

Results posted on

2025-04-30

Participant Flow

This is a a pooled analysis, stemming from two Phase I/II trials that occurred concurrently under separate investigational new drug applications (INDs) at The University of Texas MD Anderson Cancer Center (MDACC; IND 69277); and Beth Israel Deaconess Medical Center (BIDMC, IND 76179) with Dana-Farber Cancer Institute (DFCI), May 2006 to May 2009.

Results data for the two aforementioned BIDMC/DFCI and MDACC trials were combined in order to statistically complete the clinical trials. There were forty participants registered at MDACC, and eleven participants registered at BIDMC/DFCI. Of the eleven participants recruited at BIDMC/DFCI, four were ineligible.

Participant milestones

Participant milestones
Measure	MDACC Trastuzumab + RAD001 Phase I: Trastuzumab loading dose is 8 mg/kg daily; maintenance dose = 6 mg/kg once per 21 day cycle. RAD001 (Everolimus) 10 mg orally (PO) daily. Phase II: RAD001 10 mg/kg daily + Trastuzumab 6 mg/kg maintenance dose ClinicalTrials.gov ID: NCT00317720	BIDMC/DFCI Trastuzumab + RAD001 Phase I: Trastuzumab loading dose is 8 mg/kg daily; maintenance dose = 6 mg/kg once per 21 day cycle. RAD001 5 or 10 mg by mouth daily. Phase II: RAD001 10 mg/kg daily ClinicalTrials.gov ID NCT00458237
Overall Study STARTED	40	7
Overall Study COMPLETED	40	7
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Trastuzumab and RAD001 in Patients With Human Epidermal Growth Receptor 2 (HER-2) Overexpressing Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Trastuzumab + RAD001 n=47 Participants Trastuzumab loading dose is 8 mg/kg daily; maintenance dose = 6 mg/kg once per 21 day cycle. RAD001 10 mg given orally daily.
Age, Continuous	50 years n=5 Participants
Sex: Female, Male Female	47 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Hormone receptor status ER or PR positive	28 Participants n=5 Participants
Hormone receptor status ER and PR Negative	19 Participants n=5 Participants
Prior lines of trastuzumab-containing chemotherapy for metastatic breast cancer (MBC) 0	10 Participants n=5 Participants
Prior lines of trastuzumab-containing chemotherapy for metastatic breast cancer (MBC) 1	29 Participants n=5 Participants
Prior lines of trastuzumab-containing chemotherapy for metastatic breast cancer (MBC) 2	8 Participants n=5 Participants

PRIMARY outcome

Timeframe: Following two 3 week cycles of therapy

Population: At MDACC, sixteen participants total treated at 10 mg (dose level 1) in the Phase I portion of the study with the remainder thirty-four registered in Phase II. At DFCI/BIDMC, the first three participants were included in the Phase I portion of the study, the remaining four of seven registered were in Phase II.

Outcome measures

Outcome measures
Measure	Trastuzumab + RAD001 n=19 Participants Trastuzumab loading dose is 8 mg/kg daily; maintenance dose = 6 mg/kg once per 21 day cycle. RAD001 10 mg PO (by mouth) daily.
Optimal Dose of RAD001 in Combination With Trastuzumab (Phase I)	10 mg

PRIMARY outcome

Timeframe: 6 weeks

Efficacy measured by the clinical benefit response rate (CBR), defined as confirmed Complete Response (CR) plus Partial Response (PR) at any time plus Persistent Stable Disease (pSD). Confirmed CR is defined as disappearance of all target lesions at the time of radiographic evaluation; pSD was defined as SD lasting 24 weeks. Complete Response (CR): disappearance of all target lesions, and Partial Response (PR): at least a 30% decrease in the sum of longest diameter (LD) of target lesions taking as a reference the baseline sum LD. Stable Disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease taking as references the smallest sum LD since the treatment started.

Outcome measures

Outcome measures
Measure	Trastuzumab + RAD001 n=47 Participants Trastuzumab loading dose is 8 mg/kg daily; maintenance dose = 6 mg/kg once per 21 day cycle. RAD001 10 mg PO (by mouth) daily.
Clinical Benefit Response Rate (CBR) CBR	34 percentage of partcipants
Clinical Benefit Response Rate (CBR) CR	0 percentage of partcipants
Clinical Benefit Response Rate (CBR) PR	15 percentage of partcipants
Clinical Benefit Response Rate (CBR) pSD	19 percentage of partcipants

Adverse Events

Trastuzumab + RAD001

Serious events: 47 serious events

Other events: 47 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Trastuzumab + RAD001 n=47 participants at risk Trastuzumab loading dose is 8 mg/kg daily; maintenance dose = 6 mg/kg once per 21 day cycle. RAD001 10 mg PO (by mouth) daily.
Blood and lymphatic system disorders Anemia	8.5% 4/47 • Number of events 4 • Adverse events assessments graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events, version 3.0 were performed at 3-week intervals and treatment completion. Overall study period was 3 years and 4 months. Analysis including Adverse Event reporting was pooled for the two Phase I/II trials: MDACC ClinicalTrials.gov ID: NCT00317720; and BIDMC with DFCI ClinicalTrials.gov ID NCT00458237.
Blood and lymphatic system disorders Lymphopenia	27.7% 13/47 • Number of events 13 • Adverse events assessments graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events, version 3.0 were performed at 3-week intervals and treatment completion. Overall study period was 3 years and 4 months. Analysis including Adverse Event reporting was pooled for the two Phase I/II trials: MDACC ClinicalTrials.gov ID: NCT00317720; and BIDMC with DFCI ClinicalTrials.gov ID NCT00458237.
Blood and lymphatic system disorders Neutropenia	19.1% 9/47 • Number of events 9 • Adverse events assessments graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events, version 3.0 were performed at 3-week intervals and treatment completion. Overall study period was 3 years and 4 months. Analysis including Adverse Event reporting was pooled for the two Phase I/II trials: MDACC ClinicalTrials.gov ID: NCT00317720; and BIDMC with DFCI ClinicalTrials.gov ID NCT00458237.
Blood and lymphatic system disorders Thrombocytopenia	8.5% 4/47 • Number of events 4 • Adverse events assessments graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events, version 3.0 were performed at 3-week intervals and treatment completion. Overall study period was 3 years and 4 months. Analysis including Adverse Event reporting was pooled for the two Phase I/II trials: MDACC ClinicalTrials.gov ID: NCT00317720; and BIDMC with DFCI ClinicalTrials.gov ID NCT00458237.
Gastrointestinal disorders Diarrhea	19.1% 9/47 • Number of events 9 • Adverse events assessments graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events, version 3.0 were performed at 3-week intervals and treatment completion. Overall study period was 3 years and 4 months. Analysis including Adverse Event reporting was pooled for the two Phase I/II trials: MDACC ClinicalTrials.gov ID: NCT00317720; and BIDMC with DFCI ClinicalTrials.gov ID NCT00458237.
General disorders Fatigue	19.1% 9/47 • Number of events 9 • Adverse events assessments graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events, version 3.0 were performed at 3-week intervals and treatment completion. Overall study period was 3 years and 4 months. Analysis including Adverse Event reporting was pooled for the two Phase I/II trials: MDACC ClinicalTrials.gov ID: NCT00317720; and BIDMC with DFCI ClinicalTrials.gov ID NCT00458237.
General disorders Hyperglycemia	27.7% 13/47 • Number of events 13 • Adverse events assessments graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events, version 3.0 were performed at 3-week intervals and treatment completion. Overall study period was 3 years and 4 months. Analysis including Adverse Event reporting was pooled for the two Phase I/II trials: MDACC ClinicalTrials.gov ID: NCT00317720; and BIDMC with DFCI ClinicalTrials.gov ID NCT00458237.
General disorders Hypokalemia	12.8% 6/47 • Number of events 6 • Adverse events assessments graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events, version 3.0 were performed at 3-week intervals and treatment completion. Overall study period was 3 years and 4 months. Analysis including Adverse Event reporting was pooled for the two Phase I/II trials: MDACC ClinicalTrials.gov ID: NCT00317720; and BIDMC with DFCI ClinicalTrials.gov ID NCT00458237.
General disorders Hyperlipidemia	8.5% 4/47 • Number of events 4 • Adverse events assessments graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events, version 3.0 were performed at 3-week intervals and treatment completion. Overall study period was 3 years and 4 months. Analysis including Adverse Event reporting was pooled for the two Phase I/II trials: MDACC ClinicalTrials.gov ID: NCT00317720; and BIDMC with DFCI ClinicalTrials.gov ID NCT00458237.
General disorders Infection	8.5% 4/47 • Number of events 4 • Adverse events assessments graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events, version 3.0 were performed at 3-week intervals and treatment completion. Overall study period was 3 years and 4 months. Analysis including Adverse Event reporting was pooled for the two Phase I/II trials: MDACC ClinicalTrials.gov ID: NCT00317720; and BIDMC with DFCI ClinicalTrials.gov ID NCT00458237.
General disorders Mucositis	19.1% 9/47 • Number of events 9 • Adverse events assessments graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events, version 3.0 were performed at 3-week intervals and treatment completion. Overall study period was 3 years and 4 months. Analysis including Adverse Event reporting was pooled for the two Phase I/II trials: MDACC ClinicalTrials.gov ID: NCT00317720; and BIDMC with DFCI ClinicalTrials.gov ID NCT00458237.
General disorders Transaminitis	4.3% 2/47 • Number of events 2 • Adverse events assessments graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events, version 3.0 were performed at 3-week intervals and treatment completion. Overall study period was 3 years and 4 months. Analysis including Adverse Event reporting was pooled for the two Phase I/II trials: MDACC ClinicalTrials.gov ID: NCT00317720; and BIDMC with DFCI ClinicalTrials.gov ID NCT00458237.
Vascular disorders Thrombosis/embolism	4.3% 2/47 • Number of events 2 • Adverse events assessments graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events, version 3.0 were performed at 3-week intervals and treatment completion. Overall study period was 3 years and 4 months. Analysis including Adverse Event reporting was pooled for the two Phase I/II trials: MDACC ClinicalTrials.gov ID: NCT00317720; and BIDMC with DFCI ClinicalTrials.gov ID NCT00458237.

Other adverse events

Other adverse events
Measure	Trastuzumab + RAD001 n=47 participants at risk Trastuzumab loading dose is 8 mg/kg daily; maintenance dose = 6 mg/kg once per 21 day cycle. RAD001 10 mg PO (by mouth) daily.
Blood and lymphatic system disorders Anemia	36.2% 17/47 • Number of events 17 • Adverse events assessments graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events, version 3.0 were performed at 3-week intervals and treatment completion. Overall study period was 3 years and 4 months. Analysis including Adverse Event reporting was pooled for the two Phase I/II trials: MDACC ClinicalTrials.gov ID: NCT00317720; and BIDMC with DFCI ClinicalTrials.gov ID NCT00458237.
Blood and lymphatic system disorders Lymphopenia	27.7% 13/47 • Number of events 13 • Adverse events assessments graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events, version 3.0 were performed at 3-week intervals and treatment completion. Overall study period was 3 years and 4 months. Analysis including Adverse Event reporting was pooled for the two Phase I/II trials: MDACC ClinicalTrials.gov ID: NCT00317720; and BIDMC with DFCI ClinicalTrials.gov ID NCT00458237.
Blood and lymphatic system disorders Neutropenia	27.7% 13/47 • Number of events 13 • Adverse events assessments graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events, version 3.0 were performed at 3-week intervals and treatment completion. Overall study period was 3 years and 4 months. Analysis including Adverse Event reporting was pooled for the two Phase I/II trials: MDACC ClinicalTrials.gov ID: NCT00317720; and BIDMC with DFCI ClinicalTrials.gov ID NCT00458237.
Blood and lymphatic system disorders Thrombocytopenia	12.8% 6/47 • Number of events 6 • Adverse events assessments graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events, version 3.0 were performed at 3-week intervals and treatment completion. Overall study period was 3 years and 4 months. Analysis including Adverse Event reporting was pooled for the two Phase I/II trials: MDACC ClinicalTrials.gov ID: NCT00317720; and BIDMC with DFCI ClinicalTrials.gov ID NCT00458237.
General disorders Fatigue	48.9% 23/47 • Number of events 23 • Adverse events assessments graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events, version 3.0 were performed at 3-week intervals and treatment completion. Overall study period was 3 years and 4 months. Analysis including Adverse Event reporting was pooled for the two Phase I/II trials: MDACC ClinicalTrials.gov ID: NCT00317720; and BIDMC with DFCI ClinicalTrials.gov ID NCT00458237.
General disorders Hyperglycemia	19.1% 9/47 • Number of events 9 • Adverse events assessments graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events, version 3.0 were performed at 3-week intervals and treatment completion. Overall study period was 3 years and 4 months. Analysis including Adverse Event reporting was pooled for the two Phase I/II trials: MDACC ClinicalTrials.gov ID: NCT00317720; and BIDMC with DFCI ClinicalTrials.gov ID NCT00458237.
General disorders Hypokalemia	12.8% 6/47 • Number of events 6 • Adverse events assessments graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events, version 3.0 were performed at 3-week intervals and treatment completion. Overall study period was 3 years and 4 months. Analysis including Adverse Event reporting was pooled for the two Phase I/II trials: MDACC ClinicalTrials.gov ID: NCT00317720; and BIDMC with DFCI ClinicalTrials.gov ID NCT00458237.
General disorders Hyperlipidemia	19.1% 9/47 • Number of events 9 • Adverse events assessments graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events, version 3.0 were performed at 3-week intervals and treatment completion. Overall study period was 3 years and 4 months. Analysis including Adverse Event reporting was pooled for the two Phase I/II trials: MDACC ClinicalTrials.gov ID: NCT00317720; and BIDMC with DFCI ClinicalTrials.gov ID NCT00458237.
General disorders Infection	40.4% 19/47 • Number of events 19 • Adverse events assessments graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events, version 3.0 were performed at 3-week intervals and treatment completion. Overall study period was 3 years and 4 months. Analysis including Adverse Event reporting was pooled for the two Phase I/II trials: MDACC ClinicalTrials.gov ID: NCT00317720; and BIDMC with DFCI ClinicalTrials.gov ID NCT00458237.
General disorders Mucositis	53.2% 25/47 • Number of events 25 • Adverse events assessments graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events, version 3.0 were performed at 3-week intervals and treatment completion. Overall study period was 3 years and 4 months. Analysis including Adverse Event reporting was pooled for the two Phase I/II trials: MDACC ClinicalTrials.gov ID: NCT00317720; and BIDMC with DFCI ClinicalTrials.gov ID NCT00458237.
Skin and subcutaneous tissue disorders Rash	19.1% 9/47 • Number of events 9 • Adverse events assessments graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events, version 3.0 were performed at 3-week intervals and treatment completion. Overall study period was 3 years and 4 months. Analysis including Adverse Event reporting was pooled for the two Phase I/II trials: MDACC ClinicalTrials.gov ID: NCT00317720; and BIDMC with DFCI ClinicalTrials.gov ID NCT00458237.
General disorders Transaminitis	19.1% 9/47 • Number of events 9 • Adverse events assessments graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events, version 3.0 were performed at 3-week intervals and treatment completion. Overall study period was 3 years and 4 months. Analysis including Adverse Event reporting was pooled for the two Phase I/II trials: MDACC ClinicalTrials.gov ID: NCT00317720; and BIDMC with DFCI ClinicalTrials.gov ID NCT00458237.

Additional Information

Dr. Francisco Esteva

UT MD Anderson Cancer Center

Phone: 713-563-0742

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place