A Phase 2 interventional study of RAD001 and erlotinib in Neuroendocrine Tumors, sponsored by University of California, San Francisco. Terminated at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-09-29.
Sponsored by University of California, San Francisco · Phase 2, Interventional, and Treatment
The purpose of this study is to test how safe and effective the combination of RAD001 and erlotinib is in patients with neuroendocrine tumors.
Preclinical data suggest that concomitant inhibition of two non-redundant amplified pathways (mTOR and EGFR) can reverse drug resistance and more profoundly affect tumor growth than targeting either pathway alone. EGFR inhibitors may abrogate feedback loops that stimulate upstream signaling events such as PI3K and Akt in the face of mTOR inhibition. Although ErbB receptors signal through mTOR-dependent mechanisms, mTOR-independent ErbB receptor signaling also occurs in cancer. Furthermore, deregulation of apoptotic pathways like the PI3K/Akt/PTEN axis (e.g. via PTEN loss of function or AKT gene amplification) may lead to resistance to EGFR inhibitors. Treatment with an inhibitor of mTOR may reverse this resistance. Targeting the mTOR and EGFR pathways concurrently may more effectively inhibit tumor growth than inhibiting either pathway alone.
The compelling preclinical data, coupled with modest single agent activity seen with EGFR inhibition and mTOR inhibition in neuroendocrine tumors (NETs), provides a strong rationale for studying the activity of concomitant pathway inhibition in patients with advanced NETs. Support for this strategy also stems from the fact that EGFR inhibitors can be safety combined with mTOR inhibitors in humans. Emerging data from a phase I study of RAD001 plus erlotinib in patients with previously treated advanced non-small cell lung cancer (NSCLC) suggests that the two agents can be safely combined at the following doses: RAD001 5 mg PO q D and erlotinib 150 mg PO qD.
Of note, the original dose selections for RAD001 and erlotinib for this study stem directly from phase I studies with this combination (RAD001 5 mg PO qD plus erlotinib 150 mg PO qD). The modified dose selections (RAD001 5 mg PO qD plus erlotinib 100 mg PO qD) are the result of integrating discussions with the study sponsor, preliminary safety data from the first few patients enrolled in this study (suggesting that some patients tolerate full-dose therapy and others do not) and additional phase I data suggesting that the maximum tolerated dose (MTD) in some patient populations is lower than in others, e.g. the MTD in breast cancer patients is RAD001 2.5 mg PO qD and erlotinib 100 mg PO QD (Mayer et al. American Society of Clinical Oncology (ASCO) 2009 Breast Cancer Symposium, Abstract #254).
676 studies on the registry are indexed under Neuroendocrine Tumors; 169 are open to participants now.
This study's enrollment of 17 is below the median of 42 across 464 interventional studies indexed under Neuroendocrine Tumors.
Browse Neuroendocrine Tumors studies →University of California, San Francisco is the lead sponsor of 2,133 studies on the registry; 376 are open to participants now.
Of its 262 completed or terminated interventional studies of FDA-regulated products, 196 (75%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Each 28 day cycle: RAD001: 5 mg per day by mouth (self-administered) Erlotinib: 100 mg per day by mouth (self-administered)
Drug: RAD001 · Drug: erlotinib
5 mg/day PO (oral)
Also known as: Everolimus
100 mg/day (oral)
Also known as: Tarceva
Objective Response Rate (ORR)
Objective response is defined as complete response (CR) or partial response (PR) assessed using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. The primary analysis population is based on efficacy-evaluable patients, defined as those patients who receive at least one cycle of RAD001 plus erlotinib and undergo at least one post-baseline response assessment or die while on therapy.
Time frame: Up to 2 years
Number of Patients With Dose-limiting Toxicity (DLT)
Primary safety analysis will be conducted after the first 16 patients have had potential for completion of two cycles of protocol therapy. All patients receiving at least one dose of protocol therapy will be included in the analyses. All patients with treatment-related, Grade 3 or higher adverse events according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3 resulting in a DLT will be reported.
Time frame: Up to 9 months
Duration of Objective Response
Duration of objective response will be defined as the time from the initial documentation of response to documented disease progression or death from any cause on study
Time frame: Up to 2 years
Overall Survival
Overall survival will be defined as the time from first day of treatment until death
Time frame: Up to 3 years
Median Progression-Free Survival (PFS)
PFS will be defined as the time from the first day of treatment and documented objective response to time of progression or death from any cause, whichever occurs first
Time frame: Up to 3 years
Time to Progression
Time to disease progression will be defined as the time from baseline until documented disease progression or death (whichever occurs first).
Time frame: Up to 3 years
Time to Treatment Failure (TTF)
Time to treatment failure will be defined as the time from first day of treatment until study discontinuation (for any cause).
Time frame: Up to 3 years
| Milestone | RAD001 and Erlotinib |
|---|---|
| Started | 17 |
| Completed | 17 |
| Not completed | 0 |
Objective response is defined as complete response (CR) or partial response (PR) assessed using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. The primary analysis population is based on efficacy-evaluable patients, defined as those patients who receive at least one cycle of RAD001 plus erlotinib and undergo at least one post-baseline response assessment or die while on therapy.
| Participants | RAD001 Plus Erlotinib |
|---|---|
| Objective Response Rate (ORR) | 0 |
Primary safety analysis will be conducted after the first 16 patients have had potential for completion of two cycles of protocol therapy. All patients receiving at least one dose of protocol therapy will be included in the analyses. All patients with treatment-related, Grade 3 or higher adverse events according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3 resulting in a DLT will be reported.
| Participants | RAD001 and Erlotinib |
|---|---|
| Number of Patients With Dose-limiting Toxicity (DLT) | 8 |
Duration of objective response will be defined as the time from the initial documentation of response to documented disease progression or death from any cause on study
| months | RAD001 and Erlotinib |
|---|---|
| Duration of Objective Response | NA |
Overall survival will be defined as the time from first day of treatment until death
No measurements were reported for this outcome.
PFS will be defined as the time from the first day of treatment and documented objective response to time of progression or death from any cause, whichever occurs first
No measurements were reported for this outcome.
Time to disease progression will be defined as the time from baseline until documented disease progression or death (whichever occurs first).
No measurements were reported for this outcome.
Time to treatment failure will be defined as the time from first day of treatment until study discontinuation (for any cause).
No measurements were reported for this outcome.
Collected over Up to 3 years. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| RAD001 Plus Erlotinib | 6/17 (35.3%) | 4/17 (23.5%) | 17/17 (100%) |
| Event | RAD001 Plus Erlotinib |
|---|---|
| DiarrheaGastrointestinal disorders | 1/17 |
| Edema: limbVascular disorders | 1/17 |
| CreatinineInvestigations | 1/17 |
| Pain - BackMusculoskeletal and connective tissue disorders | 1/17 |
| Pain - Extremity-limbMusculoskeletal and connective tissue disorders | 1/17 |
| Incontinence, urinaryRenal and urinary disorders | 1/17 |
| Renal failureRenal and urinary disorders | 1/17 |
| Alkaline phosphataseInvestigations | 1/17 |
| Pain - Other - Right upper quadrant painInvestigations | 1/17 |
| Pain - Abdomen NOSGastrointestinal disorders | 1/17 |
| Event | RAD001 Plus Erlotinib |
|---|---|
| DiarrheaGastrointestinal disorders | 15/17 |
| StomatitisGastrointestinal disorders | 13/17 |
| FatigueGeneral disorders | 13/17 |
| Rash: acne/acneiformSkin and subcutaneous tissue disorders | 11/17 |
| AnorexiaMetabolism and nutrition disorders | 11/17 |
| Dry SkinSkin and subcutaneous tissue disorders | 11/17 |
| Weight LossInvestigations | 9/17 |
| Hemorrhage, pulmonary/upper respiratory - NoseRespiratory, thoracic and mediastinal disorders | 9/17 |
| DysgeusiaNervous system disorders | 9/17 |
| PruritusSkin and subcutaneous tissue disorders | 9/17 |
| Age, Customized(Participants) | RAD001 and Erlotinib |
|---|---|
| 20-29 years | 1 |
| 30-39 years | 0 |
| 40-49 years | 2 |
| 50-59 years | 2 |
| 60-69 years | 12 |
| Sex: Female, Male(Participants) | RAD001 and Erlotinib |
|---|---|
| Female | 8 |
| Male | 9 |
| Ethnicity (NIH/OMB)(Participants) | RAD001 and Erlotinib |
|---|---|
| Hispanic or Latino | 0 |
| Not Hispanic or Latino | 16 |
| Unknown or Not Reported | 1 |
| Race (NIH/OMB)(Participants) | RAD001 and Erlotinib |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 1 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 1 |
| White | 15 |
| More than one race | 0 |
| Unknown or Not Reported | 0 |
| Region of Enrollment(Participants) | RAD001 and Erlotinib |
|---|---|
| United States | 17 |
| Neuroendocrine Tumor Type(Participants) | RAD001 and Erlotinib |
|---|---|
| Carcinoid Neuroendocrine Tumor | 9 |
| Pancreatic neuroendocrine tumor (PNET) | 8 |
Plan to share: No
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University of California, San Francisco