RAD001 and Erlotinib in Patients With Neuroendocrine Tumors

NCT00843531 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 084511NCI-2011-01291
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Neuroendocrine Tumors

Keywords

neuroendocrine; islet cell; carcinoid; pancreatic neuroendocrine; paraganglioma; pheochromocytoma; RAD001; everolimus; erlotinib; Tarceva

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 2 years

Secondary Outcomes (6)

• Number of Patients With Dose-limiting Toxicity (DLT)

  Up to 9 months

• Duration of Objective Response

  Up to 2 years

• Overall Survival

  Up to 3 years

• Median Progression-Free Survival (PFS)

  Up to 3 years

• Time to Progression

  Up to 3 years

Study Arms (1)

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)

Drug: RAD001; Drug: erlotinib

Interventions

RAD001 DRUG

5 mg/day PO (oral)

Also known as: Everolimus

RAD001 and erlotinib

erlotinib DRUG

100 mg/day (oral)

Also known as: Tarceva

RAD001 and erlotinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \>=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
• 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

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• University of California, San Francisco: lead
• Genentech, Inc.: collaborator
• Novartis Pharmaceuticals: collaborator
• The V Foundation for Cancer Research: collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94115, United States

Location

MeSH Terms

Conditions

Neuroendocrine Tumors; Carcinoid Tumor; Paraganglioma; Pheochromocytoma

Interventions

Everolimus; Erlotinib Hydrochloride

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

Study was terminated earlier than expected due to insufficient efficacy at interim analysis and overall low enrollment

Results Point of Contact

• Title: Emily Bergsland, MD
• Organization: University of California, San Francisco

Emily.Bergsland@ucsf.edu

(415) 514-6520

Study Officials

• Emily K. Bergsland, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: February 12, 2009
• First Posted: February 13, 2009
• Study Start: June 25, 2009
• Primary Completion: July 16, 2013
• Study Completion: August 20, 2016
• Last Updated: September 29, 2020
• Results First Posted: September 29, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)