Neuroendocrine TumorsPhase 2NCT00843531
RAD001 and Erlotinib in Patients With Neuroendocrine Tumors
A Phase 2 study testing RAD001 and erlotinib in people with Neuroendocrine Tumors, run by University of California, San Francisco at 1 site in United States.
Trial summary
The purpose of this study is to test how safe and effective the combination of RAD001 and erlotinib is in patients with neuroendocrine tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neuroendocrine Tumors
- What is being tested?
- RAD001 and erlotinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Jun 2009to 20 Aug 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- >=1 measurable disease site per RECIST, not previously irradiated (if previous radiation to marker lesion(s), need evidence of PD)
- Histologic dx of well- to moderately-differentiated NET: low- or intermediate-grade, islet cell carcinoma, pancreatic NET, carcinoid, atypical carcinoid, paraganglioma, pheochromocytoma. No longer enrolling carcinoid patients as of 4/25/2011.
- ≥4 wks since completion of prior investigational drug tx or other tx(radiation, chemotherapy, immunotherapy, antibody-based tx); recovery from acute toxicities of prior tx
- Eastern Cooperative Oncology Group (ECOG) ≤2
- Absolute Neutrophil Count (ANC) ≥1500/μL
- Plts ≥100,000/μL
Show all 16Show fewer
- Hgb >9 gm/dL
- Total bilirubin ≤2.0 mg/dL or 1.5X upper limit of normal (ULN)
- Serum transaminases ≤2.5x ULN (≤5xULN if liver mets)
- Serum Cr ≤2.0 mg/dL or 1.5X ULN
- Fasting serum glucose <150 mg/dL or <1.5x ULN
- Fasting serum cholesterol ≤300 mg/dL OR ≤7.75 mmol/L AND fasting triglycerides ≤2.5xULN
- International Normalized Ratio (INR) ≤1.5
- Written informed consent, compliance w/study requirements
- Archived tissue if available
- Negative urine/serum pregnancy test w/in 7 days prior to Day 1
Who cannot join
- Poorly differentiated NET, high-grade NET, adenocarcinoid, goblet cell carcinoid, small cell carcinoma
- Major surgery or traumatic injury w/in 4 wks, inadequate recovery from side effects of any surgery, or likely to require major surgery during study
- Liver-directed therapy w/in 2 mths of enrollment. Prior tx w/ radiotherapy (including radiolabeled spheres, cyberknife, hepatic arterial embolization (w/ or w/o chemotherapy), cryotherapy/ablation) allowed if areas of measurable disease being used for the study are not affected, or if PD can clearly be documented in the area
- Prior tx w/ EGFR inhibitor or mTOR inhibitor
- Known hypersensitivity to RAD001 or other rapamycins
- Chronic, systemic tx w/ corticosteroids or another immunosuppressive agent (topical or inhaled corticosteroids are allowed)
Show all 24Show fewer
- Immunization w/ attenuated live vaccines w/in 1 wk of study entry or during study
- Uncontrolled brain or leptomeningeal mets, including pts who continue to require glucocorticoids for brain or leptomeningeal mets
- Other malignancies w/in the past 3 years except for adequately treated carcinoma of the cervix, basal/squamous cell skin carcinomas, or other in situ cancer
- Severe and/or uncontrolled intercurrent medical conditions or other conditions that may affect study participation, including, but not limited to:
- Severely impaired lung function (spirometry and Diffusing capacity of the lungs for carbon monoxide (DLCO) that is 50% of the normal predicted value and/or O2 saturation ≤88% at rest on room air)
- Symptomatic congestive heart failure (CHF) of New York Heart Association (NYHA) Class III or IV
- Unstable angina pectoris, symptomatic CHF, myocardial infarction w/in 6 months of Day 1, uncontrolled cardiac arrhythmia or any other significant cardiac disease
- Uncontrolled diabetes (fasting serum glucose ≥ 150 mg/dL or >1.5x upper limit of normal (ULN))
- Any active (acute or chronic) or severe infection, disorder, or nonmalignant medical illness that is uncontrolled or whose control may be jeopardized by study tx
- Liver disease
- Hx of HIV seropositivity or other immunocompromised state
- GI function impairment or disease that may alter absorption of RAD001 or erlotinib
- Active, bleeding diathesis or on oral anti-vitamin K medication (patients needing anticoagulation must use low molecular weight heparin (LMWH))
- Hx of other disease, metabolic dysfunction, or physical exam or lab finding giving reasonable suspicion of disease/condition that contraindicates study tx, might affect study results or puts the pt at high risk
- Pregnant or breast feeding females
- Adults of reproductive potential not willing to use effective methods of birth control during tx and ≥8 wks after completing tx
- Inability to comply w/ objectives and procedures
- Inability to comply w/ concomitant medication restrictions
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, San Francisco
San Francisco, California, 94115
About this study
Official title: A Phase II Study to Evaluate the Safety and Efficacy of RAD001 Plus Erlotinib in Patients With Well- to Moderately-Differentiated Neuroendocrine Tumors
The purpose of this study is to test how safe and effective the combination of RAD001 and erlotinib is in patients with neuroendocrine tumors.
Read the detailed description
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).
- Conditions
- Neuroendocrine Tumors
- Being tested
- RAD001, erlotinib
- Keywords
- neuroendocrine, islet cell, carcinoid, pancreatic neuroendocrine, paraganglioma, pheochromocytoma, RAD001, everolimus, erlotinib, Tarceva
- Medical subject headings
- Neuroendocrine Tumors, Carcinoid Tumor, Paraganglioma, Pheochromocytoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RAD001Drug
Also called Everolimus
5 mg/day PO (oral)
erlotinibDrug
Also called Tarceva
100 mg/day (oral)
| Study group | Role | What they receive |
|---|---|---|
| RAD001 and erlotinib | Experimental | Each 28 day cycle:
RAD001: 5 mg per day by mouth (self-administered) Erlotinib: 100 mg per day by mouth (self-administered) Receives: Drug: RAD001; Drug: erlotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 2 years
Secondary outcomes (6)
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.
Measured: 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
Measured: Up to 2 years
Overall Survival
Overall survival will be defined as the time from first day of treatment until death
Measured: 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
Measured: 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).
Measured: 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).
Measured: Up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2009 (estimated)
- Study start25 Jun 2009
- Primary completion16 Jul 2013
- Study completion20 Aug 2016
Why it stopped: Low Accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Neuroendocrine TumorsStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc., Novartis Pharmaceuticals, The V Foundation for Cancer Research
- Responsible party
- Principal investigator, Emily Bergsland, University of California, San Francisco
- Investigators
- Emily K. Bergsland, MD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00843531
- Sponsor's protocol ID
- 084511
- Other IDs
- NCI-2011-01291
- Status last verified
- Sep 2020
- First submitted
- 12 Feb 2009
- Last updated
- 29 Sep 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study to Evaluate the Safety and Efficacy of RAD001 Plus Erlotinib in Patients With Well- to Moderately-Differentiated Neuroendocrine Tumors
- ClinicalTrials.gov ID
- NCT00843531
- Acronym / sponsor ID
- 084511
- Conditions
- Neuroendocrine Tumors
- Keywords
- neuroendocrine, islet cell, carcinoid, pancreatic neuroendocrine, paraganglioma, pheochromocytoma, RAD001, everolimus
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low Accrual
- Enrolment
- 17 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- Genentech, Inc., Novartis Pharmaceuticals, The V Foundation for Cancer Research
- Study start
- 25 Jun 2009 (actual)
- Primary completion
- 16 Jul 2013 (actual)
- Study completion
- 20 Aug 2016 (actual)
- First posted
- 13 Feb 2009 (estimated)
- Results
- Posted 29 Sep 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to test how safe and effective the combination of RAD001 and erlotinib is in patients with neuroendocrine tumors.
Detailed description
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| RAD001 and erlotinib | Experimental | Drug: RAD001, Drug: erlotinibEach 28 day cycle: RAD001: 5 mg per day by mouth (self-administered) Erlotinib: 100 mg per day by mouth (self-administered) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- >=1 measurable disease site per RECIST, not previously irradiated (if previous radiation to marker lesion(s), need evidence of PD)
- Histologic dx of well- to moderately-differentiated NET: low- or intermediate-grade, islet cell carcinoma, pancreatic NET, carcinoid, atypical carcinoid, paraganglioma, pheochromocytoma. No longer enrolling carcinoid patients as of 4/25/2011.
- ≥4 wks since completion of prior investigational drug tx or other tx(radiation, chemotherapy, immunotherapy, antibody-based tx); recovery from acute toxicities of prior tx
- Eastern Cooperative Oncology Group (ECOG) ≤2
- Absolute Neutrophil Count (ANC) ≥1500/μL
Key exclusion criteria (24 listed)
- Poorly differentiated NET, high-grade NET, adenocarcinoid, goblet cell carcinoid, small cell carcinoma
- Major surgery or traumatic injury w/in 4 wks, inadequate recovery from side effects of any surgery, or likely to require major surgery during study
- Liver-directed therapy w/in 2 mths of enrollment. Prior tx w/ radiotherapy (including radiolabeled spheres, cyberknife, hepatic arterial embolization (w/ or w/o chemotherapy), cryotherapy/ablation) allowed if areas of measurable disease being used for the study are not affected, or if PD can clearly be documented in the area
- Prior tx w/ EGFR inhibitor or mTOR inhibitor
- Known hypersensitivity to RAD001 or other rapamycins
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RAD001Also: Everolimus5 mg/day PO (oral) | Drug | RAD001 and erlotinib |
| erlotinibAlso: Tarceva100 mg/day (oral) | Drug | RAD001 and erlotinib |
Primary outcome
Objective Response Rate (ORR)
Time frame: Up to 2 years
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.
6 secondary outcomes
Number of Patients With Dose-limiting Toxicity (DLT)
Time frame: Up to 9 months
Duration of Objective Response
Time frame: Up to 2 years
Overall Survival
Time frame: Up to 3 years
Median Progression-Free Survival (PFS)
Time frame: Up to 3 years
Time to Progression
Time frame: Up to 3 years
Time to Treatment Failure (TTF)
Time frame: Up to 3 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Neuroendocrine Tumors
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingPhase 1
IL-17 Blockade to Decrease irAEs (REPLAY)
Metastatic Melanoma
RecruitingPhase 2
A UGT1A1 Genotype-Directed Study of Belinostat Pharmacokinetics and Toxicity
Carcinoma, Neuroendocrine, Tumor, Neuroendocrine
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
RecruitingPhase 3
Somatostatin Analogues vs. Observation After Peptide Receptor Radionuclide Therapy (PRRT) in Nonfunctional Neuroendocrine Neoplasms
Neuroendocrine Neoplasm, Gastroenteropancreatic Neuroendocrine Neoplasm
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Emily K. Bergsland, MD principal investigator
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing RAD001 and erlotinib in people with Neuroendocrine Tumors, run by University of California, San Francisco at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 29 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Sep 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) (time frame: Up to 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2020.