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A Randomized Phase II Study to Assess the Efficacy of Pemetrexed or Sunitinib (NSC # 736511, IND # 74019) or Pemetrexed Plus Sunitinib in the Second-Line Treatment of Advanced Non-Small Cell Lung Cancer


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Recurrent Non-small Cell Lung Cancer, Stage IIIB Non-small Cell Lung Cancer, Stage IV Non-small Cell Lung Cancer

Thank you

Trial Information

A Randomized Phase II Study to Assess the Efficacy of Pemetrexed or Sunitinib (NSC # 736511, IND # 74019) or Pemetrexed Plus Sunitinib in the Second-Line Treatment of Advanced Non-Small Cell Lung Cancer


PRIMARY OBJECTIVES:

I. To compare the 18-week progression-free survival rate in patients with stage IIIB or IV
non-small cell lung cancer treated with pemetrexed disodium alone vs sunitinib malate alone
vs pemetrexed disodium in combination with sunitinib malate as second-line therapy.

SECONDARY OBJECTIVES:

I. To compare the progression-free survival of patients treated with these regimens.

II. To compare the response rate, duration of response, rate of stable disease, and overall
survival of patients treated with these regimens.

III. To characterize the toxicity profiles of these regimens in these patients. IV. To
determine the response rate, duration of response, rate of stable disease, and overall
survival of patients who receive sunitinib malate in the third-line setting.

V. To assess the toxicity of sunitinib malate when administered in the third-line setting in
these patients.

VI. To test changes in tumor size at 6 weeks as an early predictor of therapeutic activity
of these second-line treatment regimens.

OUTLINE: This is a multicenter study. Patients are stratified according to ECOG performance
status (0 vs 1), disease stage (IIIB vs IV), and gender. Patients are randomized to 1 of 3
treatment arms.

ARM I: Patients receive pemetrexed disodium IV over 10 minutes on day 1. Courses repeat
every 21 days in the absence of disease progression or unacceptable toxicity. Patients with
documented disease progression may then receive sunitinib malate as in arm II as third-line
therapy.

ARM II: Patients receive oral sunitinib malate once daily on days 1-21. Courses repeat every
21 days in the absence of disease progression or unacceptable toxicity. Patients with
documented disease progression may then receive pemetrexed disodium as in arm I as
third-line therapy.

ARM III: Patients receive pemetrexed disodium IV over 10 minutes on day 1 and oral sunitinib
malate once daily on days 1-21. Courses repeat every 21 days in the absence of disease
progression or unacceptable toxicity. Patients with documented disease progression may then
receive third-line therapy at the discretion of the treating physician.

After completion of study therapy, patients are followed every 6 weeks until disease
progression and then every 6 months for 2 years.


Inclusion Criteria:



- Histologically or cytologically confirmed non-small cell lung cancer (NSCLC)

- Stage IIIB or IV disease

- Must have evidence of disease progression after first-line therapy

- Measurable or non-measurable disease

- Measurable disease is defined as lesions that can be accurately measured in ≥ 1
dimension as ≥ 2 cm by conventional techniques or ≥ 1 cm by spiral CT scan

- Non-measurable disease is defined as all other lesions, including small lesions
(i.e., longest diameter < 20 mm by conventional techniques or < 10 mm by spiral
CT scan) and truly non-measurable lesions, including any of the following:

- Bone lesions

- Leptomeningeal disease

- Ascites

- Pleural or pericardial effusion

- Lymphangitis cutis or pulmonis

- Abdominal mass that are not confirmed and followed by imaging techniques

- Cystic lesions

- No cavitary lesions

- No pleural effusions or ascites detectable on physical exam

- No symptomatic or untreated CNS metastases

- Patients with CNS metastases are eligible provided the metastases were
definitively treated with surgery or radiotherapy AND patient is asymptomatic
and off steroids or on a stable dose of steroids for 2 weeks prior to study
entry

- Concurrent enrollment on CALGB-580702 (imaging study) required

- ECOG performance status 0-1

- Granulocytes ≥ 1,500/μL

- Platelet count ≥ 100,000/μL

- Magnesium ≥ lower limit of normal

- Bilirubin ≤ 1.5 times upper limit of normal (ULN)

- AST and ALT ≤ 2.5 times ULN

- PTT ≤ 1.5 times ULN

- INR ≤ 1.5

- Creatinine clearance ≥ 45 mL/min

- Quantitative urine protein < 30 mg/dL OR ≤ 1+ on dipstick

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 6 months after
completion of study therapy

- QTc interval ≤ 500 msec within the past 2 years

- No ongoing cardiac dysrhythmias

- No atrial fibrillation

- No symptomatic congestive heart failure within the past 12 months

- NYHA class I heart failure allowed

- Patients with a history of NYHA class II heart failure are eligible provided at
least 1 of the following criteria is met:

- Asymptomatic on treatment

- Previously treated with anthracycline

- Previously treated with central thoracic radiotherapy that included the
heart in the radiotherapy port

- No myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass
graft or stenting, cerebrovascular accident, or transient ischemic attack within the
past year

- No hypertension that cannot be controlled by medications (i.e., blood pressure >
150/100 mm Hg despite optimal medical therapy)

- No history of venous thrombosis, pulmonary embolism, or hypercoagulopathy syndrome

- No history of pulmonary hemorrhage, bleeding diathesis, or evidence of hemoptysis

- Patients with blood-tinged or blood-streaked sputum are eligible provided the
hemoptysis is < 5 mL of blood per episode and < 10 mL of blood per 24-hour
period, in the best estimate of the investigator

- No abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, or
serious or non-healing wound, ulcer, or bone fracture within the past 28 days

- History of hypothyroidism allowed provided patient is currently euthyroid

- At least 28 days since prior first-line therapy

- No more than one prior chemotherapy regimen (platinum or non-platinum based) in
the first-line setting for NSCLC

- Prior adjuvant therapy allowed provided the patient received one regimen in the
advanced setting

- At least 4 weeks since prior EGFR inhibitors or bevacizumab

- At least 28 days since prior major surgery (6 weeks since resection of brain
metastases)

- At least 14 days since prior radiotherapy

- More than 7 days since prior and no concurrent CYP3A4 inhibitors, including any of
the following:

- Azole antifungals (e.g., ketoconazole or itraconazole)

- Diltiazem

- Clarithromycin

- Erythromycin

- Verapamil

- Delavirdine

- HIV protease inhibitors (e.g., indinavir, saquinavir, ritonavir, atazanavir, or
nelfinavir)

- More than 12 days since prior and no concurrent CYP3A4 inducers, including any of the
following:

- Rifampin

- Rifabutin

- Carbamazepine

- Phenobarbital

- Phenytoin

- St. John's wort

- Efavirenz

- Tipranavir

- No prior pemetrexed disodium

- No prior VEGFR inhibitors (e.g., semaxanib, SU6668, AZ6474, sunitinib malate,
vatalanib, cediranib, AEE-788, or sorafenib)

- No concurrent chronic daily treatment with aspirin (> 325 mg/day) or non-steroidal
anti-inflammatory agents known to inhibit platelet function

- No concurrent dipyridamole (Persantine), ticlopidine (Ticlid), clopidogrel (Plavix),
and/or cilostazol (Pletal)

- No concurrent therapeutic anticoagulation for thromboembolic disease

- Concurrent low-dose warfarin (≤ 2 mg/day) allowed for prophylaxis of thrombosis

- No concurrent agents with proarrhythmic potential (e.g., quinidine, procainamide,
disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone, indapamide, or
flecainide)

- No concurrent hormonal therapy, except steroids for adrenal failure, hormones for
non-disease-related conditions (e.g., insulin for diabetes), or dexamethasone used
intermittently as an antiemetic or as premedication for pemetrexed disodium

- No other concurrent chemotherapy

- No concurrent palliative radiotherapy

- No concurrent G-CSF (filgrastim), GM-CSF (sargramostim), and/or pegfilgrastim

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression-free survival (PFS) rate defined as proportion of patients who remain alive and progression free after initial administration of the treatment.

Outcome Description:

All patients will be followed up for the 18-week PFS regardless of whether they have completed the protocol treatment. Comparisons of treatment effects in terms of 18-week PFS rate will be conducted using a one-sided Fisher's exact test. The comparisons will follow the multiple testing procedure as described above. As a supplementary analysis, stratified comparisons of 18-week PFS rates between the experimental arms versus the control arm will be done using the Mantel-Haenszel chi-square test.

Outcome Time Frame:

At 18 weeks

Safety Issue:

No

Principal Investigator

Rebecca Suk Heist

Investigator Role:

Principal Investigator

Investigator Affiliation:

Cancer and Leukemia Group B

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2009-00471

NCT ID:

NCT00698815

Start Date:

April 2008

Completion Date:

Related Keywords:

  • Recurrent Non-Small Cell Lung Cancer
  • Stage IIIB Non-Small Cell Lung Cancer
  • Stage IV Non-Small Cell Lung Cancer
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms

Name

Location

University of Iowa Hospitals and ClinicsIowa City, Iowa  52242
Massachusetts General Hospital Cancer CenterBoston, Massachusetts  02114
Memorial Hospital of South BendSouth Bend, Indiana  46601
Dana-Farber Cancer InstituteBoston, Massachusetts  02115
Hartford HospitalHartford, Connecticut  06102-5037
University of Nebraska Medical CenterOmaha, Nebraska  68198-3330
New Hanover Regional Medical CenterWilmington, North Carolina  28402-9025
Southern California Permanente Medical GroupDowney, California  90242
Brigham and Women's HospitalBoston, Massachusetts  02115
Cancer Centers of the CarolinasGreenville, South Carolina  29605
Elkhart General HospitalElkhart, Indiana  46515
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical CenterColumbus, Ohio  43210-1240
University Medical Center of Southern NevadaLas Vegas, Nevada  89102
Alta Bates Summit Medical Center - Summit CampusOakland, California  94609
Beebe Medical CenterLewes, Delaware  19958
Great Plains Regional Medical CenterNorth Platte, Nebraska  69101-6598
Mountainview MedicalBerlin, Vermont  05602
Highland General HospitalOakland, California  94602
Center for Cancer Care and ResearchSt. Louis, Missouri  63141
Memorial Hospital of Rhode IslandPawtucket, Rhode Island  02860
Union Hospital of Cecil CountyElkton MD, Maryland  21921
Cancer Centers of the Carolinas - Grove CommonsGreenville, South Carolina  29605
Cancer Centers of the Carolinas - SenecaSeneca, South Carolina  29672
Cancer Centers of the Carolinas - SpartanburgSpartanburg, South Carolina  29307
Washington Hospital CenterWashington, District of Columbia  20010
Saint Francis Medical CenterGrand Island, Nebraska  68802
McLeod Regional Medical CenterFlorence, South Carolina  29501
Newton-Wellesley HospitalNewton, Massachusetts  02462
University of North CarolinaChapel Hill, North Carolina  27599
East Bay Radiation Oncology CenterCastro Valley, California  94546
Contra Costa Regional Medical CenterMartinez, California  94553-3156
Larry G Strieff MD Medical CorporationOakland, California  94609
Glens Falls HospitalGlens Falls, New York  12801
Holy Cross HospitalFort Lauderdale, Florida  33308
El Camino HospitalMountain View, California  94040
University of California at San DiegoLa Jolla, California  92093
Kaiser Permanente Medical CenterVallejo, California  94589
University Of VermontBurlington,, Vermont  05403
Kaiser PermanenteSacramento, California  
Cancer Centers of the Carolinas - EasleyEasley, South Carolina  29640
University of Chicago Comprehensive Cancer CenterChicago, Illinois  60637-1470
Northern Indiana Cancer Research ConsortiumSouth Bend, Indiana  
Wake Forest University Health SciencesWinston-Salem, North Carolina  27157
Valley Medical Oncology Consultants-Castro ValleyCastro Valley, California  94546
Eden Hospital Medical CenterCastro Valley, California  94546
Valley Medical Oncology Consultants-FremontFremont, California  94538
Bay Area Breast Surgeons IncOakland, California  94609
Bay Area Tumor Institution CCOPOakland, California  94609
Tom K Lee IncOakland, California  94609
Valley Medical Oncology ConsultantsPleasanton, California  94588
Valley Care Health System - PleasantonPleasanton, California  94588
Doctors Medical Center- JC Robinson Regional Cancer CenterSan Pablo, California  94806
Middlesex HospitalMiddletown, Connecticut  06457
Lombardi Comprehensive Cancer Center at Georgetown UniversityWashington, District of Columbia  20057
Hematology Oncology Associates-Quad CitiesBettendorf, Iowa  52722
Lakeland HospitalSt. Joseph, Michigan  49085
Missouri Baptist Medical CenterSaint Louis, Missouri  63131
Nevada Cancer Research Foundation CCOPLas Vegas, Nevada  89106
Exeter HospitalExeter, New Hampshire  03833
Cooper Hospital University Medical CenterCamden, New Jersey  08103
State University of New York Upstate Medical UniversitySyracuse, New York  13210
Wayne Memorial HospitalGoldsboro, North Carolina  27534
Marion L Shepard Cancer CenterWashington, North Carolina  27889
Greenville Memorial HospitalGreenville, South Carolina  29605
Jupiter Medical CenterJupiter, Florida  33458
University of IllinoisChicago, Illinois  60612
Elkhart ClinicElkhart, Indiana  46515
Mount Sinai Medical Center CCOPMiami Beach, Florida  33140
Jesse Brown Veterans Affairs Medical CenterChicago, Illinois  60612
Michiana Hematology Oncology PC-ElkhartElkhart, Indiana  46514
Michiana Hematology Oncology PC-PlymouthPlymouth, Indiana  46563
Michiana Hematology Oncology PC-South BendSouth Bend, Indiana  46601
Michiana Hematology Oncology-PC WestvilleWestville, Indiana  46391
Michiana Hematology Oncology PC-NilesNiles, Michigan  49120
University of Missouri - Ellis FischelColumbia, Missouri  65203
Syracuse Veterans Administration Medical CenterSyracuse, New York  13210
Cancer Centers of the Carolinas - FarisGreenville, South Carolina  29605
Cancer Centers of the Carolinas-Greer Radiation OncologyGreer, South Carolina  29650
Cancer Centers of the Carolinas-Greer Medical OncologyGreer, South Carolina  29650
University of Minnesota Medical Center-FairviewMinneapolis, Minnesota  55455
Kaiser Anaheim Medical CenterAnaheim, California  92807
Kaiser Permanente Medical Group - Baldwin ParkBaldwin Park, California  91706
Kaiser Foundation HospitalBellflower, California  90706
Kaiser Permanente HospitalFontana, California  92335
Kaiser Permanente - Harbor CityHarbor City, California  90710
Kaiser Permanente-West Los AngelesLos Angeles, California  90034
Kaiser Permanente - Panorama CityPanorama City, California  91402
Palchak David MDPismo Beach, California  93449
Kaiser Permanente at San DiegoSan Diego, California  92120
Kaiser Permanente Health CareSan Marcos, California  92069
Capital Region Medical Center-Goldschmidt Cancer CenterJefferson City, Missouri  65109
Comprehensive Cancer Care PCSaint Louis, Missouri  63141
Kaiser Permanente-MissionSan Diego, California  92108
VA Medical Center - University of IowaIowa City, Iowa  52246
Michiana Hematology Oncology PC-MishawakaMishawaka, Indiana  46545-1470
Marie Yeager Cancer CenterSaint Joseph, Michigan  49085
Community Howard Regional HealthKokomo, Indiana  46904
Indiana University Health La Porte HospitalLa Porte, Indiana  46350
Saint Joseph Regional Medical Center-MishawakaMishawaka, Indiana  46545-1470
Christiana Care Health System-Christiana HospitalNewark, Delaware  19718
Self Regional HealthcareGreenwood, South Carolina  29646
Dana-Farber/Brigham and Women's Cancer Center at Milford RegionalMilford, Massachusetts  01757