Pancreatic Neuroendocrine TumorPhase 1/2NCT00576680

RAD001 and Temozolomide in Patients With Advanced Pancreatic Neuroendocrine Tumors

A Phase 1/2 study testing RAD001 and Temozolomide in people with Pancreatic Neuroendocrine Tumor, run by Dana-Farber Cancer Institute at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This research study will test the safety of RAD001 in combination with temozolomide. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Pancreatic Neuroendocrine Tumor
What is being tested?: RAD001 and Temozolomide
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 43 participants
Where: 3 sitesUnited States
Study dates: May 2008to 29 Mar 2019
Phase: Phase 1/2
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

Locally unresectable or metastatic pancreatic neuroendocrine tumor
Radiologic, operative, or pathology reports should document a pancreatic location of tumor
Patients must have confirmed low-grade or intermediate-grade neuroendocrine carcinoma
Patients must have at least one measurable site of disease according to RECIST criteria that has not been preciously irradiated
18 years of age or older
Minimum of two weeks since any major surgery, completion of radiation, or completion of all prior systemic anticancer therapy

Show all 13Show fewer

Prior treatment with chemotherapy is allowed, with the exception of prior treatment with temozolomide or dacarbazine
No Prior therapy with RAD001 or any other mTOR inhibitor
ECOG Performance status 0,1 or 2
Life expectancy 12 weeks or more
Adequate bone marrow, liver and renal function as outlined in the protocol
Negative serum pregnancy test
Fasting serum cholesterol as outlined in protocol

Who cannot join

Prior treatment with any investigational drug within the preceding 4 weeks
Chronic treatment with systemic steroids or another immunosuppressive agent
Patients should not receive immunization with attenuated live vaccines during study period or within 1 week of study entry
Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases
Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinoma of the skin
Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study

Show all 10Show fewer

Women who are pregnant or breast feeding
Patients who have received prior treatment with an mTOR inhibitor or temozolomide
Patients with known hypersensitivity to RAD001 or other rapamycins or to its excipients
History of noncompliance to medical regimens

Trial locations and contacts

3 sites in 1 country.

United States3 sites

Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215

Other trials in United States

About this study

Official title: Phase I/II Study of RAD001 in Combination With Temozolomide in Patients With Advanced Pancreatic Neuroendocrine Tumors

This research study will test the safety of RAD001 in combination with temozolomide.

Read the detailed description

Participants will take RAD001 by mouth daily. They will also take temozolomide by mouth daily for one week, followed by a one-week break period. This one-week on/one week off schedule for temozolomide will continue for the duration of the treatment.
After the first month of treatment, there will be a 7-day observation period during which no study medication will be taken to observe for any side effects.
During all treatment cycles (1 cycle is 28 days in length) participants will have a physical exam and will be asked questions about their general health and specific questions about any problems they may be experiencing. Initially, participants will come in every other week. At each of these visits, blood work will be taken to monitor the participants health.
After every 2 months of treatment, participants will have a CT scan or MRI done to see how the medication is working.

Conditions: Pancreatic Neuroendocrine Tumor
Being tested: RAD001, Temozolomide
Keywords: RAD001, temozolomide
Medical subject headings: Adenoma, Islet Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

RAD001Drug
Given orally once a day
TemozolomideDrug
Also called Temodar
Taken orally once a day for one week followed by a one-week break period

Study groups in NCT00576680
Study group	Role	What they receive
Temozolomide with RAD001	Experimental	Not described Receives: Drug: RAD001; Drug: Temozolomide

What is being measured

The primary outcome is the main question the study is designed to answer.

Response Rate
To determine the objective response rate by RECIST criteria of RAD001 in combination with temozolomide in patients with advanced pancreatic neuroendocrine tumors. Partial response (PR) by these criteria is defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter. Progressive disease (PD) is defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions. Stable Disease (SD) is defined as neither sufficient decrease to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum longest diameter since the treatment started.
Measured: 2 years

Secondary outcomes (2)

Progression-free Survival
To determine progression-free survival when RAD001 is given in combination with temozolomide in patients with advanced pancreatic neuroendocrine tumors. Progression-free survival is defined as time from start of therapy until disease progression, as defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST), as 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions, or death.
Measured: 2 years
To Determine the Safety and Tolerability of This Drug Combination.
To determine the safety and tolerability of RAD001 when given in combination with temozolomide in patients with advanced pancreatic neuroendocrine tumors.
Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

May 200829 Mar 2019

First posted19 Dec 2007 (estimated)
Study startMay 2008
Primary completion29 Mar 2019
Study completion29 Mar 2019

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 Pancreatic Neuroendocrine TumorStudies of the same condition, open and under way.
More trials run by Dana-Farber Cancer InstituteThe 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 1/2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 43 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00576680
Sponsor's protocol ID: 07-325
Status last verified: Jun 2020
First submitted: 17 Dec 2007
Last updated: 9 Jul 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Pancreatic Neuroendocrine Tumor trials

Study at a glance

From the registry record, last updated by the sponsor on 9 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase I/II Study of RAD001 in Combination With Temozolomide in Patients With Advanced Pancreatic Neuroendocrine Tumors
ClinicalTrials.gov ID: NCT00576680
Acronym / sponsor ID: 07-325
Conditions: Pancreatic Neuroendocrine Tumor
Keywords: RAD001, temozolomide
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 43 participants (actual)
Lead sponsor: Dana-Farber Cancer InstituteUniversity, hospital or other
Collaborators: Beth Israel Deaconess Medical Center, Brigham and Women's Hospital, Massachusetts General Hospital, Novartis, Schering-Plough
Study start: May 2008
Primary completion: 29 Mar 2019 (actual)
Study completion: 29 Mar 2019 (actual)
First posted: 19 Dec 2007 (estimated)
Results: Posted 9 Jul 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

This research study will test the safety of RAD001 in combination with temozolomide.

Detailed description

Participants will take RAD001 by mouth daily. They will also take temozolomide by mouth daily for one week, followed by a one-week break period. This one-week on/one week off schedule for temozolomide will continue for the duration of the treatment.
After the first month of treatment, there will be a 7-day observation period during which no study medication will be taken to observe for any side effects.
During all treatment cycles (1 cycle is 28 days in length) participants will have a physical exam and will be asked questions about their general health and specific questions about any problems they may be experiencing. Initially, participants will come in every other week. At each of these visits, blood work will be taken to monitor the participants health.
After every 2 months of treatment, participants will have a CT scan or MRI done to see how the medication is working.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Temozolomide with RAD001	Experimental	Drug: RAD001, Drug: Temozolomide

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (13 listed)

Locally unresectable or metastatic pancreatic neuroendocrine tumor
Radiologic, operative, or pathology reports should document a pancreatic location of tumor
Patients must have confirmed low-grade or intermediate-grade neuroendocrine carcinoma
Patients must have at least one measurable site of disease according to RECIST criteria that has not been preciously irradiated
18 years of age or older

Key exclusion criteria (10 listed)

Prior treatment with any investigational drug within the preceding 4 weeks
Chronic treatment with systemic steroids or another immunosuppressive agent
Patients should not receive immunization with attenuated live vaccines during study period or within 1 week of study entry
Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases
Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinoma of the skin

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
RAD001Given orally once a day	Drug	Temozolomide with RAD001
TemozolomideAlso: TemodarTaken orally once a day for one week followed by a one-week break period	Drug	Temozolomide with RAD001

Primary outcome

Response Rate
Time frame: 2 years
To determine the objective response rate by RECIST criteria of RAD001 in combination with temozolomide in patients with advanced pancreatic neuroendocrine tumors. Partial response (PR) by these criteria is defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter. Progressive disease (PD) is defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions. Stable Disease (SD) is defined as neither sufficient decrease to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum longest diameter since the treatment started.

2 secondary outcomes

Progression-free Survival
Time frame: 2 years
To Determine the Safety and Tolerability of This Drug Combination.
Time frame: 2 years

Results and safety

Results posted to the registry on 9 Jul 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Temozolomide and Everolimus	43	43

Primary outcome: Response Rate

Time frame: 2 years. Count of participants. Unit: Participants

Measure	Temozolomide and Everolimus n = 40
Value	16

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: Participants were followed for development of adverse events for the entire duration while receiving treatment and for 30 days following their last dose of study treatment. Patients in this trial received a median of 8.5 four-week treatment cycles (range, 1-28). Each participant was followed for adverse events for 30 days following his or her last dose of study treatment.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Temozolomide and Everolimus	15 of 43 (34.9%)	43 of 43 (100%)	2 of 43

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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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.

Jennifer Chan, MD, PhD principal investigator

Dana-Farber Cancer Institute

3 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing RAD001 and Temozolomide in people with Pancreatic Neuroendocrine Tumor, run by Dana-Farber Cancer Institute at 3 sites 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 13 inclusion and 10 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: finished, as of the sponsor's last update on 9 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 9 Jul 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?

Response Rate (time frame: 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00576680.

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 9 Jul 2020.