Unspecified Adult Solid Tumor, Protocol SpecificPhase 1NCT00390000
Vatalanib and Pemetrexed Disodium in Treating Patients With Advanced Solid Tumors
A Phase 1 study testing vatalanib, pemetrexed disodium and pharmacological study in people with Unspecified Adult Solid Tumor, Protocol Specific, run by Mayo Clinic at 1 site in United States.
Trial summary
RATIONALE: Vatalanib and pemetrexed disodium may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Vatalanib may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving vatalanib together with pemetrexed disodium may kill more tumor cells. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Unspecified Adult Solid Tumor, Protocol Specific
- What is being tested?
- vatalanib, pemetrexed disodium and pharmacological study
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Jan 2007to 4 Aug 2016
- 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
- Willingness to return to Mayo Clinic Rochester for follow up
- Women of childbearing potential and men must agree to use adequate contraception (barrier method of birth control) prior to study entry, duration of study participation, and for at least 30 days after the last administration of study medication
- ECOG performance status (PS) 0, 1, or 2
- Histologic proof of advanced solid tumor that has no known standard therapy that is potentially curative or definitely capable of extending life expectancy upon registration.
- Mandatory translational research (MTD patients only): willingness to provide the biologic specimens as required by the protocol; willingness to undergo brachial artery ultrasound measurements
- ANC >= 1500/uL
Show all 16Show fewer
- Hgb >= 9 g/dL
- PLT >= 100,000/uL
- AST =< 3 x ULN or AST =< 5 x ULN if liver involvement
- Calculated creatinine clearance >= 45 ml/min
- Total bilirubin =< 1.5 x upper limit of normal (ULN)
- Random urine protein:osmolality ratio =< 0.40 OR total urinary protein =< 500 mg and measured creatinine clearance (CrCl) >= 45 mL/min from a 24-hour urine collection
- Patients should have no contraindications to the intake of folic acid, vitamin B12 or dexamethasone
- For patients with pleural/peritoneal/pericardial effusions: If patient is asymptomatic but the effusion volume is approximated to be > 500 mL or produces measurable objective changes related to the effusion (e.g., echocardiographic ventricular compression, hypoxia on pulse oximetry, etc.), effusion should be drained
- Able to permanently discontinue aspirin dose of >=1.3 grams/day >=10 days before through >= 10 days after pemetrexed disodium treatment
- Life expectancy >= 12 weeks
Who cannot join
- Symptomatic, untreated, or uncontrolled CNS metastases or seizure disorder; patients with CNS metastases treated with whole brain radiation (WBRT) may be enrolled after completion of WBRT; patients may begin chemotherapy as early as the next day after WBRT
- Any clinically significant infection
- Active, bleeding diathesis or on any anticoagulant
- HIV-positive patients receiving combination anti-retroviral therapy because of possible pharmacokinetic interactions with PTK/ZK
- Chemotherapy =< 3 weeks prior to registration
- Radiation to >= 30% of bone marrow
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- Immunotherapy =< 2 weeks prior to registration
- Chronic renal disease
- Acute or chronic liver disease (e.g., hepatitis, cirrhosis)
- Impairment of gastrointestinal (GI) function or GI disease since they may significantly alter the absorption of PTK/ZK (i.e., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, bowel obstruction, or inability to swallow tablets)
- Greater than (>) normal risk of bleeding or on any anticoagulant
- Pregnant, nursing, or positive pregnancy test =< 7 days prior to registration for women of childbearing potential
- Symptomatic serosal effusion (>= CTCAE v3.0 grade 2 dyspnea that is not amenable to drainage prior to registration)
- Mitomycin C/nitrosoureas, bevacizumab =< 6 weeks prior to registration
- Biologic therapy =< 2 weeks prior to registration
- Other chemotherapy, immunotherapy, hormonal therapy, radiotherapy, or any ancillary therapy considered investigational (utilized for a non-FDA approved indication and in the context of a research investigation) =< 4 weeks prior to registration
- Prolonged QTc (> 450 msec for males and > 470 msec for females) or known history of congenital or acquired prolonged QTc syndrome
- Serious condition that, in the opinion of the investigator, would compromise the patient's ability to complete the study
- Prior therapy with monoclonal antibody to VEGF, VEGF trap, small molecules with receptor tyrosine kinase activity against VEGFR, antisense oligonucleotide therapy against VEGF mRNA is allowed
- Full field radiation therapy =< 4 weeks prior to registration or limited field radiation therapy =< 2 weeks prior to registration (the site of previous radiotherapy should have evidence of progressive disease if this is the only site of disease)
- Men or women of childbearing potential who are unwilling to employ adequate contraception (a barrier method of birth control) (oral, implantable, or injectable contraceptives may be affected by cytochrome p450 interactions and are, therefore, not considered effective for this study)
- a) Labile hypertension, or history of poor compliance with antihypertensive medication
- d) Myocardial infarction =< 6 months prior to registration
- h) History of deep venous thrombosis or pulmonary embolism =< 2 years prior to registration
- Current use of the following drugs: amiodarone; anticoagulants (e.g., warfarin); anti-retroviral therapy (e.g., ritonavir); carbamazepine; chlorpromazine; cisapride; clarithromycin; clopidogrel; disopyramide; droperidol; erythromycin; fondaparinux; haloperidol; heparin; itraconazole; ketoconazole
- Current use of the following drugs: methadone; oral contraceptives; phenobarbital; phenytoin; procainamide; products containing grapefruit juice; quinidine; rifabutin; rifampin; sotalol; sparfloxacin; St. John's Wort; thioridazine
- i) Patients who require chronic treatment with PPI (e.g., omeprazole, lansoprazole, etc.) or H2 antagonist (e.g., ranitidine, famotidine, etc.)
- Major surgery (i.e., laparotomy), open biopsy, or significant traumatic injury =< 4 weeks prior to registration; minor surgery =< 2 weeks prior to registration; insertion of a vascular access device is not considered major or minor surgery in this regard
- b) Angina pectoris
- c) History of congestive heart failure =< 3 months prior to registration, unless ejection fraction > 45%
- f) Diabetes
- g) Interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung
- Patients who have received prior treatment using pemetrexed disodium-containing regimens =< 12 months prior to registration
- Any of the following concurrent severe and/or uncontrolled medical conditions:
- e) Cardiac arrhythmia
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase I Study of PTK/ZK in Combination With Pemetrexed Disodium (ALIMTA)
RATIONALE: Vatalanib and pemetrexed disodium may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Vatalanib may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving vatalanib together with pemetrexed disodium may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of vatalanib when given together with pemetrexed disodium 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 PTK/ZK and pemetrexed disodium when given in combination.
II. To describe the toxicities associated with the combination of PTK/ZK with pemetrexed disodium.
III. To evaluate the pharmacokinetic interaction of combination of PTK/ZK with pemetrexed disodium at the MTD (Group II).
IV. To evaluate the intracellular content of pemetrexed disodium polyglutamates as a measure of activity of pemetrexed disodium transport and activation enzymes in the MTD expansion cohort (Group II).
- To evaluate polymorphisms and gene expression of pemetrexed disodium target genes, and genes encoding enzymes involved in the transport, activation, and inactivation of pemetrexed disodium, and correlate haplotype-tagged SNPs or gene expression levels with intracellular levels of pemetrexed disodium polyglutamates, toxicity and/or efficacy or pemetrexed disodium in Group II.
VI. To evaluate pharmacogenetic, metabolic and clinical markers that may predict for hypertension induced by anti-VEGF therapy.
OUTLINE:
This is a dose-escalation study of vatalanib. Patients are assigned to 1 of 2 treatment groups.
GROUP I (dose escalation, closed to accrual 12/18/2007): Patients receive pemetrexed disodium IV over 10 minutes on day 1 and oral vatalanib twice daily on days 1-21.
GROUP II (MTD expansion group): Patients receive pemetrexed disodium IV on day 1, as in group I. Patients also receive oral vatalanib at the MTD twice daily on days 8-21 during course 1 and on days 1-21 during all subsequent courses.
In both groups, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
- Being tested
- vatalanib, pemetrexed disodium, pharmacological study, ultrasound imaging
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
vatalanibDrug
Also called CGP-79787, PTK787/ZK 222584
Given orally
pemetrexed disodiumDrug
Also called ALIMTA, LY231514, MTA
Given IV
Also called pharmacological studies
Correlative study
ultrasound imagingProcedure or surgery
Also called ultrasonography, ultrasound, ultrasound test
Correlative study
| Study group | Role | What they receive |
|---|---|---|
| Arm I | Experimental | See Detailed Description Receives: Drug: vatalanib; Drug: pemetrexed disodium; Other: pharmacological study; Procedure: ultrasound imaging |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall toxicity incidence as well as toxicity profiles as measured by dose level, patient, and primary disease site as measured by NCI CTCAE v3.0
Dose-limiting toxicity and maximum tolerated dose (MTD) of vatalanib when administered with pemetrexed disodium as measured by NCI CTCAE v3.0
Pharmacokinetics of treatment, including AUC, C-max, half-life, and clearance obtained in patients treated at the MTD
Measured: At different time points on day 1 of each course
Expression of functionally relevant polymorphisms in genes that encode proteins involved in the transport and activation of pemetrexed disodium in patients treated at the MTD
Correlation of expression of these polymorphisms with clinical outcomes (toxicity, response, or progression status) in patients treated at the MTD
Relation of gene expression and polymorphisms to the intracellular content of pemetrexed disodium
Secondary outcomes (2)
Response (complete and partial response, stable and progressive disease) in patients with measurable disease
Response profile as measured by dose level and by primary disease site
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2006 (estimated)
- Study start25 Jan 2007
- Primary completion4 Aug 2016
- Study completion4 Aug 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Unspecified Adult Solid Tumor, Protocol SpecificStudies 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
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Julian Molina, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00390000
- Sponsor's protocol ID
- MC0515
- Other IDs
- NCI-2009-01316, MC0515, P30CA015083
- Status last verified
- Apr 2019
- First submitted
- 18 Oct 2006
- Last updated
- 8 Apr 2019
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 8 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of PTK/ZK in Combination With Pemetrexed Disodium (ALIMTA)
- ClinicalTrials.gov ID
- NCT00390000
- Acronym / sponsor ID
- MC0515
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 25 Jan 2007 (actual)
- Primary completion
- 4 Aug 2016 (actual)
- Study completion
- 4 Aug 2016 (actual)
- First posted
- 19 Oct 2006 (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: Vatalanib and pemetrexed disodium may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Vatalanib may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving vatalanib together with pemetrexed disodium may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of vatalanib when given together with pemetrexed disodium in treating patients with advanced solid tumors.
Detailed description
OBJECTIVES:
- To determine the dose limiting toxicity (DLT) and maximally tolerated dose (MTD) of PTK/ZK and pemetrexed disodium when given in combination.
II. To describe the toxicities associated with the combination of PTK/ZK with pemetrexed disodium.
III. To evaluate the pharmacokinetic interaction of combination of PTK/ZK with pemetrexed disodium at the MTD (Group II).
IV. To evaluate the intracellular content of pemetrexed disodium polyglutamates as a measure of activity of pemetrexed disodium transport and activation enzymes in the MTD expansion cohort (Group II).
- To evaluate polymorphisms and gene expression of pemetrexed disodium target genes, and genes encoding enzymes involved in the transport, activation, and inactivation of pemetrexed disodium, and correlate haplotype-tagged SNPs or gene expression levels with intracellular levels of pemetrexed disodium polyglutamates, toxicity and/or efficacy or pemetrexed disodium in Group II.
VI. To evaluate pharmacogenetic, metabolic and clinical markers that may predict for hypertension induced by anti-VEGF therapy.
OUTLINE:
This is a dose-escalation study of vatalanib. Patients are assigned to 1 of 2 treatment groups.
GROUP I (dose escalation, closed to accrual 12/18/2007): Patients receive pemetrexed disodium IV over 10 minutes on day 1 and oral vatalanib twice daily on days 1-21.
GROUP II (MTD expansion group): Patients receive pemetrexed disodium IV on day 1, as in group I. Patients also receive oral vatalanib at the MTD twice daily on days 8-21 during course 1 and on days 1-21 during all subsequent courses.
In both groups, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
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: vatalanib, Drug: pemetrexed disodium, Other: pharmacological study, 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 (16 listed)
- Willingness to return to Mayo Clinic Rochester for follow up
- Women of childbearing potential and men must agree to use adequate contraception (barrier method of birth control) prior to study entry, duration of study participation, and for at least 30 days after the last administration of study medication
- ECOG performance status (PS) 0, 1, or 2
- Histologic proof of advanced solid tumor that has no known standard therapy that is potentially curative or definitely capable of extending life expectancy upon registration.
- Mandatory translational research (MTD patients only): willingness to provide the biologic specimens as required by the protocol; willingness to undergo brachial artery ultrasound measurements
Key exclusion criteria (35 listed)
- Symptomatic, untreated, or uncontrolled CNS metastases or seizure disorder; patients with CNS metastases treated with whole brain radiation (WBRT) may be enrolled after completion of WBRT; patients may begin chemotherapy as early as the next day after WBRT
- Any clinically significant infection
- Active, bleeding diathesis or on any anticoagulant
- HIV-positive patients receiving combination anti-retroviral therapy because of possible pharmacokinetic interactions with PTK/ZK
- Chemotherapy =< 3 weeks prior to registration
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 |
|---|---|---|
| vatalanibAlso: CGP-79787, PTK787/ZK 222584Given orally | Drug | Arm I |
| pemetrexed disodiumAlso: ALIMTA, LY231514, MTAGiven IV | Drug | Arm I |
| pharmacological studyAlso: pharmacological studiesCorrelative study | Other | Arm I |
| ultrasound imagingAlso: ultrasonography, ultrasound, ultrasound testCorrelative study | Procedure or surgery | Arm I |
Primary outcome
Overall toxicity incidence as well as toxicity profiles as measured by dose level, patient, and primary disease site as measured by NCI CTCAE v3.0
Dose-limiting toxicity and maximum tolerated dose (MTD) of vatalanib when administered with pemetrexed disodium as measured by NCI CTCAE v3.0
Pharmacokinetics of treatment, including AUC, C-max, half-life, and clearance obtained in patients treated at the MTD
Time frame: At different time points on day 1 of each course
Expression of functionally relevant polymorphisms in genes that encode proteins involved in the transport and activation of pemetrexed disodium in patients treated at the MTD
Correlation of expression of these polymorphisms with clinical outcomes (toxicity, response, or progression status) in patients treated at the MTD
Relation of gene expression and polymorphisms to the intracellular content of pemetrexed disodium
2 secondary outcomes
Response (complete and partial response, stable and progressive disease) in patients with measurable disease
Response profile as measured by dose level and by primary disease site
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 8 Apr 2019.
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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 Molina 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 vatalanib, pemetrexed disodium and pharmacological study in people with Unspecified Adult Solid Tumor, Protocol Specific, 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 16 inclusion and 35 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 8 Apr 2019. 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?
Overall toxicity incidence as well as toxicity profiles as measured by dose level, patient, and primary disease site as measured by NCI CTCAE v3.0. The study lists 6 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 8 Apr 2019.