Neoplasm MetastasesPhase 1NCT01122199
Study of RAD001 + AMG479 for Patients With Advanced Solid Tumors
A Phase 1 study testing RAD001 + AMG479 in people with Neoplasm Metastases, run by Shadia Jalal at 1 site in United States.
Trial summary
The purpose of this study is to test the safety of the combination of two drugs called RAD001 and AMG479. This study will see what effects (good and bad) RAD001 and AMG479 have on cancer. This study will also find the highest doses of RAD001 and AMG479 that can be given without causing severe side effects. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasm Metastases
- What is being tested?
- RAD001 + AMG479
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteUnited States
- Study dates
- 14 May 2010to 19 Jan 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Histological or cytological proof of metastatic solid tumor refractory to standard therapies, or for which no standard therapies are available.
- Patients in the expansion cohort must have a measurable site of disease according to RECIST (v 1.0)
- Laboratory values must be obtained within protocol limits and obtained within 14 days prior to registration
- Patients must have disease which is not amenable to potentially curative surgical resection of metastatic disease (curative metastasectomy).
- Must be willing to provide metastatic tissue biopsy samples (may be paraffin embedded) at baseline
- Must be willing to undergo a metastatic tissue biopsy after 2 cycles of therapy to perform pharmacodynamic research biomarkers testing.
- Subjects must be willing and able to abstain from using strong or moderate CYP3A4 inhibitors or inducers during the study period.
Who cannot join
- No symptomatic brain metastasis
- No prior treatment with an mTOR inhibitor or with an IGF-1R inhibitor
- No known history of diabetes mellitus
- No thrombosis or vascular ischemic events within the last twelve months
- No chronic treatment with systemic steroids or another immunosuppressive agent
- No active bleeding or a pathological condition that is associated with a high risk of bleeding
Show all 10Show fewer
- No known history of HIV seropositivity
- No known history of Hepatitis B or Hepatitis C seropositivity
- No known hypersensitivity to AMG 479, RAD001 (everolimus), other rapamycins (sirolimus, temsirolimus), or to its excipients
- No planned immunization with attenuated live viruses during the study period
Trial locations and contacts
1 site in 1 country.
United States1 site
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, 46202
About this study
Official title: Phase I Study of mTOR Inhibitor RAD001 in Combination With IGF-1R Inhibitor AMG479 for Patients With Advanced Solid Tumors
The purpose of this study is to test the safety of the combination of two drugs called RAD001 and AMG479. This study will see what effects (good and bad) RAD001 and AMG479 have on cancer. This study will also find the highest doses of RAD001 and AMG479 that can be given without causing severe side effects.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the maximum tolerated (MTD) and recommended Phase II doses for AMG479 (ganitumab) and RAD001 (everolimus) in patients with refractory solid tumors.
II. To determine the safety and toxicity of AMG479 and RAD001.
SECONDARY OBJECTIVES:
- To determine preliminary antitumor efficacy of AMG479 and RAD001 in solid tumors: response and stable disease rates, duration of response and of stable disease, time to progression (TTP) and overall survival (OS).
II. For all patients, to analyze tumor and blood samples for pharmacodynamic biomarkers related to IGF-1R and mTOR signaling: pAkt, pS6, p-4EBP1, PTEN, IGF-1, IGF-2, pIGF-1R and IGFBP3 and correlate with response and stable disease.
III. For all patients, to analyze the pharmacokinetic profile (PK) for RAD001 and AMG479, and correlate with response/stable disease and pharmacodynamic markers.
IV. To evaluate the effects of RAD001 on AMG 479 pharmacokinetics.
OUTLINE: This is a dose-escalation study.
Patients receive everolimus orally (PO) once daily (QD) on days 1-28 (days 1-7 and 16-28 of course 1 only) and ganitumab intravenously (IV) over 60 minutes on days 1 and 15 (day 15 of course 1 only). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at day 30, every 3 months for 2 years from registration for study treatment, every 6 months for years 3-5, and then annually thereafter.
- Conditions
- Neoplasm Metastases
- Being tested
- RAD001 + AMG479
- Medical subject headings
- Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RAD001 + AMG479Drug
Also called everolimus + ganitumab
Escalating doses of RAD001 + AMG479. Starting cohort will be 5 mg RAD001 once daily, continuous + AMG479 12 mg/kg on Day 1 and 15 of each 28 day cycle.
| Study group | Role | What they receive |
|---|---|---|
| Open Label | Experimental | RAD001+ AMG479 Receives: Drug: RAD001 + AMG479 |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the maximum tolerated (MTD) and recommended Phase II doses for AMG479 and RAD001 in patients with refractory solid tumors
Measured: 1 year
To evaluate the grade and severity of adverse events as a measure of safety and toxicity
Measured: 2 years
Secondary outcomes (1)
To determine preliminary antitumor efficacy of AMG479 and RAD001 in solid tumors
response and stable disease rates, duration of response and of stable disease, time to progression (TTP) and overall survival (OS)
Measured: 5-10 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2010 (estimated)
- Study start14 May 2010
- Primary completion19 Jan 2015
- Study completion19 Jan 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neoplasm MetastasesStudies of the same condition, open and under way.
- 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shadia Jalal
- Sponsor type
- University, hospital or other
- Collaborators
- Amgen, Novartis
- Responsible party
- Sponsor-investigator, Shadia Jalal, Indiana University
- Investigators
- Shadia I Jalal, MD, Study chair, Indiana University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01122199
- Sponsor's protocol ID
- 1002-16; IUCRO-0287
- Status last verified
- May 2017
- First submitted
- 7 May 2010
- Last updated
- 10 May 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of mTOR Inhibitor RAD001 in Combination With IGF-1R Inhibitor AMG479 for Patients With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT01122199
- Acronym / sponsor ID
- 1002-16; IUCRO-0287
- Conditions
- Neoplasm Metastases
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Shadia JalalUniversity, hospital or other
- Collaborators
- Amgen, Novartis
- Study start
- 14 May 2010 (actual)
- Primary completion
- 19 Jan 2015 (actual)
- Study completion
- 19 Jan 2015 (actual)
- First posted
- 13 May 2010 (estimated)
- Results
- Not posted in the source record
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 the safety of the combination of two drugs called RAD001 and AMG479. This study will see what effects (good and bad) RAD001 and AMG479 have on cancer. This study will also find the highest doses of RAD001 and AMG479 that can be given without causing severe side effects.
Detailed description
PRIMARY OBJECTIVES:
- To determine the maximum tolerated (MTD) and recommended Phase II doses for AMG479 (ganitumab) and RAD001 (everolimus) in patients with refractory solid tumors.
II. To determine the safety and toxicity of AMG479 and RAD001.
SECONDARY OBJECTIVES:
- To determine preliminary antitumor efficacy of AMG479 and RAD001 in solid tumors: response and stable disease rates, duration of response and of stable disease, time to progression (TTP) and overall survival (OS).
II. For all patients, to analyze tumor and blood samples for pharmacodynamic biomarkers related to IGF-1R and mTOR signaling: pAkt, pS6, p-4EBP1, PTEN, IGF-1, IGF-2, pIGF-1R and IGFBP3 and correlate with response and stable disease.
III. For all patients, to analyze the pharmacokinetic profile (PK) for RAD001 and AMG479, and correlate with response/stable disease and pharmacodynamic markers.
IV. To evaluate the effects of RAD001 on AMG 479 pharmacokinetics.
OUTLINE: This is a dose-escalation study.
Patients receive everolimus orally (PO) once daily (QD) on days 1-28 (days 1-7 and 16-28 of course 1 only) and ganitumab intravenously (IV) over 60 minutes on days 1 and 15 (day 15 of course 1 only). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at day 30, every 3 months for 2 years from registration for study treatment, every 6 months for years 3-5, and then annually thereafter.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Open Label | Experimental | Drug: RAD001 + AMG479RAD001+ AMG479 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Histological or cytological proof of metastatic solid tumor refractory to standard therapies, or for which no standard therapies are available.
- Patients in the expansion cohort must have a measurable site of disease according to RECIST (v 1.0)
- Laboratory values must be obtained within protocol limits and obtained within 14 days prior to registration
- Patients must have disease which is not amenable to potentially curative surgical resection of metastatic disease (curative metastasectomy).
- Must be willing to provide metastatic tissue biopsy samples (may be paraffin embedded) at baseline
Key exclusion criteria (10 listed)
- No symptomatic brain metastasis
- No prior treatment with an mTOR inhibitor or with an IGF-1R inhibitor
- No known history of diabetes mellitus
- No thrombosis or vascular ischemic events within the last twelve months
- No chronic treatment with systemic steroids or another immunosuppressive agent
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 |
|---|---|---|
| RAD001 + AMG479Also: everolimus + ganitumabEscalating doses of RAD001 + AMG479. Starting cohort will be 5 mg RAD001 once daily, continuous + AMG479 12 mg/kg on Day 1 and 15 of each 28 day cycle. | Drug | Open Label |
Primary outcome
To determine the maximum tolerated (MTD) and recommended Phase II doses for AMG479 and RAD001 in patients with refractory solid tumors
Time frame: 1 year
To evaluate the grade and severity of adverse events as a measure of safety and toxicity
Time frame: 2 years
1 secondary outcome
To determine preliminary antitumor efficacy of AMG479 and RAD001 in solid tumors
Time frame: 5-10 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2017.
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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.
Shadia I Jalal, MD study chair
Indiana University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing RAD001 + AMG479 in people with Neoplasm Metastases, run by Shadia Jalal 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 7 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 10 May 2017. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
To determine the maximum tolerated (MTD) and recommended Phase II doses for AMG479 and RAD001 in patients with refractory solid tumors (time frame: 1 year). The study lists 2 primary outcomes in all. 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 10 May 2017.