GastrinomaPhase 1NCT00655655
Everolimus and Vatalanib in Treating Patients With Advanced Solid Tumors
A Phase 1 study testing everolimus, vatalanib and pharmacological study in people with Gastrinoma and Glucagonoma, run by Mayo Clinic at 1 site in United States.
Trial summary
RATIONALE: Everolimus and vatalanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving everolimus together with vatalanib may kill more tumor cells. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gastrinoma, Glucagonoma, Insulinoma
- What is being tested?
- everolimus, vatalanib and pharmacological study
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 96 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2004to 11 Jan 2018
- 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
- Histologic proof of cancer that is now unresectable (solid tumors, excluding lymphoma)
- Ability to provide informed consent
- Willingness to return to Mayo Clinic Rochester for follow up
- Life expectancy >= 12 weeks
- Prior anti-VEGF therapy allowed
- Cohort IIA: Patients meeting other eligibility criteria, regardless of histopathologic diagnosis; tumor that is amenable to biopsy; willingness to provide blood specimens, undergo DCE-MRI, and undergo brachial artery ultrasound measurements as required by the protocol
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- The following laboratory values obtained =< 14 days prior to registration:
- Negative for proteinuria based on dip stick reading OR, if documentation of +1 result for protein on dip stick reading, then total urinary protein =< 500 mg and measured creatinine clearance (CrCl) >= 50 mL/min from a 24-hour urine collection
- Cohort IIB: Patients meeting other eligibility criteria AND with pathologic diagnosis of metastatic kidney cancer, neuroendocrine carcinoma, melanoma, and NSCLC; willingness to provide blood specimens required and undergo brachial artery ultrasound measurements
- The following laboratory values obtained =< 14 days prior to registration:
- ANC >= 1500/uL; Hgb >= 9 g/dL; PLT >= 100,000/uL; Total bilirubin =< 1.5 x upper limit of normal (ULN); AST =< 3 x ULN or AST =< 5 x ULN if liver involvement; Creatinine =< 1.5 x ULN; INR =< 1.4 (Cohort IIA only)
Who cannot join
- Any of the following prior therapies: Full field radiation therapy =<4 weeks prior to registration or limited field radiation therapy =< 2 weeks prior to registration; Radiation to >30% of bone marrow; Major surgery (i.e., laparotomy) =< 4 weeks prior to registration; Minor surgery =< 2 weeks prior to registration
- New York Heart Association classification III or IV
- Uncontrolled hypertension, labile hypertension or history of poor compliance with antihypertensive medication
- Active, bleeding diathesis or on any anticoagulant except patients receiving heparin for deep venous thrombosis prophylaxis (not treatment)
- CNS metastases or seizure disorder
- Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (utilized for a non-FDA-approved indication and in the context of a research investigation
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- Any concurrent severe and/or uncontrolled medical conditions which could compromise participation or pose as unnecessary risk to the patient in the study, including, but not limited, to the following: Unstable angina; Myocardial infarction =< 6 months prior to registration; Serious uncontrolled cardiac arrhythmia; Uncontrolled diabetes
- Any concurrent severe and/or uncontrolled medical conditions which could compromise participation or pose as unnecessary risk to the patient in the study, including, but not limited, to the following: Interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung; QTc > 500 msec; Patients who require chronic treatment with PPI or H2 antagonist
- Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of PTK787/ZK 222584 (i.e., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, bowel obstruction, or inability to swallow the tablets)
- Known standard therapy for the patient's disease that is potentially curative or definitely capable of extending life expectancy
- Chemotherapy =< 3 weeks; Mitomycin C/nitrosoureas =< 6 weeks; Immunotherapy =< 2 weeks; Biologic therapy =< 2 weeks; Prior investigational therapy =< 4 weeks; Full field radiation therapy =< 4 weeks or limited field radiation therapy =< 2 weeks; Radiation to > 30% of bone marrow; Major surgery (i.e., laparotomy) =< 4 weeks; or Minor surgery =< 2 weeks prior to registration
- Any of the following: pregnant women; nursing women; men or women of childbearing potential who are unwilling to employ adequate barrier contraception
- Patients on whom DCE-MRI is contraindicated (e.g., presence of MRI-incompatible metallic implants or prosthetic heart valves, pacemakers, etc.) are ineligible
- ECOG performance status (PS) 3 or 4
- Treatment with medications listed in Appendix I for which no safer or more efficacious alternative is available
- Uncontrolled infection
- Failure to fully recover from acute, reversible effects of prior chemotherapy regardless of interval since last treatment
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I Trial of the mTOR Inhibitor RAD001 in Combination With VEGF Receptor Tyrosine Kinase Inhibitor PTK787/ZK 222584 in Patients With Advanced Solid Tumors
RATIONALE: Everolimus and vatalanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving everolimus together with vatalanib may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of everolimus and vatalanib in treating patients with advanced solid tumors.
Read the detailed description
OBJECTIVES:
- To determine the dose limiting toxicity (DLT) and maximally tolerated dose (MTD) of RAD001 and once daily PTK787 when given in combination. (Cohort IA) II. To describe the toxicities associated with the combination of RAD001 and once daily PTK787. (Cohort IA) III. To evaluate the therapeutic antitumor activity of the combination of once daily PTK787 with RAD001. (Cohort IA) IV. To determine the dose limiting toxicity (DLT) and maximally tolerated dose (MTD) of RAD001 and twice daily PTK787 when given in combination. (Cohort IB) V. To describe the toxicities associated with the combination of RAD001 and twice daily PTK787. (Cohort IB) VI. To evaluate the therapeutic antitumor activity of the combination of twice daily PTK787 with RAD001. (Cohort IB) VII. To determine the MTD-Recommended Phase 2 Dose (RP2D) based on the MTD for Cohorts IA and IB. (Cohorts IA \& IB) VIII. To investigate the biological activity of the combination of PTK787 with RAD001 at the MTD-RP2D. (Cohort II) IX. To evaluate the therapeutic antitumor activity of the combination of PTK787 with RAD001 at the MTD-RP2D. (Cohort II) X. To evaluate pharmacogenetic, metabolic and clinical markers that may predict for hypertension induced by anti-VEGF therapy. (Cohort II) XI. To obtain pilot data on efficacy outcomes in patients with metastatic kidney cancer, neuroendocrine cancer, NSCLC or melanoma. (Cohort II)
OUTLINE:
Patients are assigned to 1 of 4 cohorts, according to their disease (cohort IA, IB, or IIA [any histopathologic diagnosis] vs cohort IIB [metastatic kidney cancer, neuroendocrine cancer, melanoma, or non-small cell lung cancer). Patients are initially enrolled into cohorts IA and IB until the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) are determined. Once the MTD/RP2D of everolimus and vatalanib are determined, subsequent patients are enrolled and treated in expansion cohorts IIA or IIB.
Cohorts 1A or 1B (dose escalation cohorts; closed to enrollment as of 12/6/06): Patients receive oral vatalanib once (cohort 1A) or twice (cohort 1B) daily on days 1-28 and oral everolimus once daily on days 15-28 of course 1. For all subsequent courses, patients receive oral vatalanib once (cohort 1A) or twice (cohort 1B) daily and oral everolimus once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Cohort IIA (expansion cohort treated at the MTD/RP2D): Patients receive oral everolimus once daily for 14 days followed by a 7-day rest period. Patients then receive oral vatalanib twice daily on days 1-28 and oral everolimus once daily on days 15-28 of course 1. For all subsequent courses, patients receive oral vatalanib twice daily and oral everolimus once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Cohort IIB (expansion cohort treated at the MTD/RP2D): Patients receive oral vatalanib twice daily on days 1-28 and oral everolimus once daily on days 15-28 of course 1. For all subsequent courses, patients receive oral vatalanib twice daily and oral everolimus once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed at 3 months.
- Conditions
- Gastrinoma, Glucagonoma, Insulinoma, Metastatic Gastrointestinal Carcinoid Tumor, Metastatic Pheochromocytoma, Pancreatic Polypeptide Tumor
- Being tested
- everolimus, vatalanib, pharmacological study, laboratory biomarker analysis, dynamic contrast-enhanced magnetic resonance imaging
- Medical subject headings
- Gastrinoma, Glucagonoma, Insulinoma, Pheochromocytoma, Carcinoma, Islet Cell, Melanoma, Carcinoma, Merkel Cell, Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
everolimusDrug
Also called 42-O-(2-hydroxy)ethyl rapamycin, Afinitor, RAD001
Given orally
vatalanibDrug
Also called CGP-79787, PTK787/ZK 222584
Given orally
Also called pharmacological studies
Correlative study (Cohort IIA only)
laboratory biomarker analysisOther
Correlative study (Cohorts IIA and IIB)
dynamic contrast-enhanced magnetic resonance imagingProcedure or surgery
Also called DCE-MRI
Correlative study (Cohort IIA only)
ultrasound imagingProcedure or surgery
Also called ultrasonography, ultrasound, ultrasound test
Correlative study (Cohorts IIA and IIB)
| Study group | Role | What they receive |
|---|---|---|
| Arm I | Experimental | See Detailed Description Receives: Drug: everolimus; Drug: vatalanib; Other: pharmacological study; Other: laboratory biomarker analysis; Procedure: dynamic contrast-enhanced magnetic resonance imaging; Procedure: ultrasound imaging |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose of everolimus and vatalanib (Cohort I) (Closed to enrollment as of 12/6/06)
Measured: Up to 28 days post treatment cycle
Toxicity associated with everolimus and vatalanib (Cohort I) (Closed to enrollment as of 12/6/06)
Measured: Up to 28 days post treatment cycle
Therapeutic antitumor activity of everolimus and vatalanib (Cohort I) (Closed to enrollment as of 12/6/06)
Measured: Up to 28 days post treatment cycle
Recommended phase II dose (RP2D) of everolimus and vatalanib (Cohort I) (Closed to enrollment as of 12/6/06)
Measured: After MTD (maximum tolerate dose) is determined from Phase I
Biological activity and therapeutic antitumor activity of everolimus and vatalanib when given at the MTD/RPTD (Cohort II)
Measured: Post treatment cycle
Evaluation of pharmacogenetic, metabolic, and clinical markers that may predict hypertension induced by anti-VEGF therapy (Cohort II)
Measured: Day 1 and 14 of Cycle 1 of treatment
Efficacy outcomes in patients with metastatic kidney cancer, neuroendocrine carcinoma, non-small cell lung cancer, or melanoma (Cohort II)
Measured: Post treatment cycle with MTD outcomes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2008 (estimated)
- Study startDec 2004
- Primary completion15 Sep 2009
- Study completion11 Jan 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GastrinomaStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 96 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Julian R. Molina, M.D., Ph.D., Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00655655
- Sponsor's protocol ID
- MC0414
- Other IDs
- NCI-2009-01200, MC0414
- Status last verified
- Aug 2024
- First submitted
- 9 Apr 2008
- Last updated
- 21 Aug 2024
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial of the mTOR Inhibitor RAD001 in Combination With VEGF Receptor Tyrosine Kinase Inhibitor PTK787/ZK 222584 in Patients With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT00655655
- Acronym / sponsor ID
- MC0414
- Conditions
- Gastrinoma, Glucagonoma, Insulinoma, Metastatic Gastrointestinal Carcinoid Tumor, Metastatic Pheochromocytoma, Pancreatic Polypeptide Tumor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 96 participants (estimated)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Study start
- Dec 2004 (actual)
- Primary completion
- 15 Sep 2009 (actual)
- Study completion
- 11 Jan 2018 (actual)
- First posted
- 10 Apr 2008 (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.
RATIONALE: Everolimus and vatalanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving everolimus together with vatalanib may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of everolimus and vatalanib in treating patients with advanced solid tumors.
Detailed description
OBJECTIVES:
- To determine the dose limiting toxicity (DLT) and maximally tolerated dose (MTD) of RAD001 and once daily PTK787 when given in combination. (Cohort IA) II. To describe the toxicities associated with the combination of RAD001 and once daily PTK787. (Cohort IA) III. To evaluate the therapeutic antitumor activity of the combination of once daily PTK787 with RAD001. (Cohort IA) IV. To determine the dose limiting toxicity (DLT) and maximally tolerated dose (MTD) of RAD001 and twice daily PTK787 when given in combination. (Cohort IB) V. To describe the toxicities associated with the combination of RAD001 and twice daily PTK787. (Cohort IB) VI. To evaluate the therapeutic antitumor activity of the combination of twice daily PTK787 with RAD001. (Cohort IB) VII. To determine the MTD-Recommended Phase 2 Dose (RP2D) based on the MTD for Cohorts IA and IB. (Cohorts IA \& IB) VIII. To investigate the biological activity of the combination of PTK787 with RAD001 at the MTD-RP2D. (Cohort II) IX. To evaluate the therapeutic antitumor activity of the combination of PTK787 with RAD001 at the MTD-RP2D. (Cohort II) X. To evaluate pharmacogenetic, metabolic and clinical markers that may predict for hypertension induced by anti-VEGF therapy. (Cohort II) XI. To obtain pilot data on efficacy outcomes in patients with metastatic kidney cancer, neuroendocrine cancer, NSCLC or melanoma. (Cohort II)
OUTLINE:
Patients are assigned to 1 of 4 cohorts, according to their disease (cohort IA, IB, or IIA [any histopathologic diagnosis] vs cohort IIB [metastatic kidney cancer, neuroendocrine cancer, melanoma, or non-small cell lung cancer). Patients are initially enrolled into cohorts IA and IB until the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) are determined. Once the MTD/RP2D of everolimus and vatalanib are determined, subsequent patients are enrolled and treated in expansion cohorts IIA or IIB.
Cohorts 1A or 1B (dose escalation cohorts; closed to enrollment as of 12/6/06): Patients receive oral vatalanib once (cohort 1A) or twice (cohort 1B) daily on days 1-28 and oral everolimus once daily on days 15-28 of course 1. For all subsequent courses, patients receive oral vatalanib once (cohort 1A) or twice (cohort 1B) daily and oral everolimus once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Cohort IIA (expansion cohort treated at the MTD/RP2D): Patients receive oral everolimus once daily for 14 days followed by a 7-day rest period. Patients then receive oral vatalanib twice daily on days 1-28 and oral everolimus once daily on days 15-28 of course 1. For all subsequent courses, patients receive oral vatalanib twice daily and oral everolimus once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Cohort IIB (expansion cohort treated at the MTD/RP2D): Patients receive oral vatalanib twice daily on days 1-28 and oral everolimus once daily on days 15-28 of course 1. For all subsequent courses, patients receive oral vatalanib twice daily and oral everolimus once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed at 3 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm I | Experimental | Drug: everolimus, Drug: vatalanib, Other: pharmacological study, Other: laboratory biomarker analysis, Procedure: dynamic contrast-enhanced magnetic resonance imaging, Procedure: ultrasound imagingSee Detailed Description |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Histologic proof of cancer that is now unresectable (solid tumors, excluding lymphoma)
- Ability to provide informed consent
- Willingness to return to Mayo Clinic Rochester for follow up
- Life expectancy >= 12 weeks
- Prior anti-VEGF therapy allowed
Key exclusion criteria (17 listed)
- Any of the following prior therapies: Full field radiation therapy =<4 weeks prior to registration or limited field radiation therapy =< 2 weeks prior to registration; Radiation to >30% of bone marrow; Major surgery (i.e., laparotomy) =< 4 weeks prior to registration; Minor surgery =< 2 weeks prior to registration
- New York Heart Association classification III or IV
- Uncontrolled hypertension, labile hypertension or history of poor compliance with antihypertensive medication
- Active, bleeding diathesis or on any anticoagulant except patients receiving heparin for deep venous thrombosis prophylaxis (not treatment)
- CNS metastases or seizure disorder
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 |
|---|---|---|
| everolimusAlso: 42-O-(2-hydroxy)ethyl rapamycin, Afinitor, RAD001Given orally | Drug | Arm I |
| vatalanibAlso: CGP-79787, PTK787/ZK 222584Given orally | Drug | Arm I |
| pharmacological studyAlso: pharmacological studiesCorrelative study (Cohort IIA only) | Other | Arm I |
| laboratory biomarker analysisCorrelative study (Cohorts IIA and IIB) | Other | Arm I |
| dynamic contrast-enhanced magnetic resonance imagingAlso: DCE-MRICorrelative study (Cohort IIA only) | Procedure or surgery | Arm I |
| ultrasound imagingAlso: ultrasonography, ultrasound, ultrasound testCorrelative study (Cohorts IIA and IIB) | Procedure or surgery | Arm I |
Primary outcome
Maximum tolerated dose of everolimus and vatalanib (Cohort I) (Closed to enrollment as of 12/6/06)
Time frame: Up to 28 days post treatment cycle
Toxicity associated with everolimus and vatalanib (Cohort I) (Closed to enrollment as of 12/6/06)
Time frame: Up to 28 days post treatment cycle
Therapeutic antitumor activity of everolimus and vatalanib (Cohort I) (Closed to enrollment as of 12/6/06)
Time frame: Up to 28 days post treatment cycle
Recommended phase II dose (RP2D) of everolimus and vatalanib (Cohort I) (Closed to enrollment as of 12/6/06)
Time frame: After MTD (maximum tolerate dose) is determined from Phase I
Biological activity and therapeutic antitumor activity of everolimus and vatalanib when given at the MTD/RPTD (Cohort II)
Time frame: Post treatment cycle
Evaluation of pharmacogenetic, metabolic, and clinical markers that may predict hypertension induced by anti-VEGF therapy (Cohort II)
Time frame: Day 1 and 14 of Cycle 1 of treatment
Efficacy outcomes in patients with metastatic kidney cancer, neuroendocrine carcinoma, non-small cell lung cancer, or melanoma (Cohort II)
Time frame: Post treatment cycle with MTD outcomes
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 21 Aug 2024.
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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.
Julian R. Molina, M.D., Ph.D. principal investigator
Mayo Clinic
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 everolimus, vatalanib and pharmacological study in people with Gastrinoma and Glucagonoma, run by Mayo Clinic 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 11 inclusion and 17 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 21 Aug 2024. 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?
Maximum tolerated dose of everolimus and vatalanib (Cohort I) (Closed to enrollment as of 12/6/06) (time frame: Up to 28 days post treatment cycle). The study lists 7 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 21 Aug 2024.