Vatalanib and Pemetrexed Disodium in Treating Patients With Advanced Solid Tumors

NCT00390000 | Completed Phase 1 DMC

• 3 other identifiers: MC0515NCI-2009-01316P30CA015083
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Outcome Measures

Primary Outcomes (6)

• 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

  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

Study Arms (1)

Arm I

EXPERIMENTAL

See Detailed Description

Drug: vatalanib; Drug: pemetrexed disodium; Other: pharmacological study; Procedure: ultrasound imaging

Interventions

vatalanib DRUG

Given orally

Also known as: CGP-79787, PTK787/ZK 222584

Arm I

pemetrexed disodium DRUG

Given IV

Also known as: ALIMTA, LY231514, MTA

Arm I

pharmacological study OTHER

Correlative study

Also known as: pharmacological studies

Arm I

ultrasound imaging PROCEDURE

Correlative study

Also known as: ultrasonography, ultrasound, ultrasound test

Arm I

Eligibility Criteria

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

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Interventions

vatalanib; Pemetrexed; High-Energy Shock Waves

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Ultrasonic Waves; Sound; Radiation, Nonionizing; Radiation; Physical Phenomena

Study Officials

• Julian Molina

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2006
• First Posted: October 19, 2006
• Study Start: January 25, 2007
• Primary Completion: August 4, 2016
• Study Completion: August 4, 2016
• Last Updated: April 8, 2019

Record last verified: 2019-04

Locations

US (1)