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A Non-Randomized, Multi-Center Open Label Phase II Study of Pazopanib and Pemetrexed or Pazopanib Alone In Stage IIIB/IV Non-Squamous Non-Small Cell Lung Cancer After Progression on First Line Therapy Containing Bevacizumab.


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Lung Cancer

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Trial Information

A Non-Randomized, Multi-Center Open Label Phase II Study of Pazopanib and Pemetrexed or Pazopanib Alone In Stage IIIB/IV Non-Squamous Non-Small Cell Lung Cancer After Progression on First Line Therapy Containing Bevacizumab.


OBJECTIVES:

Primary

- To estimate the disease-control rate (complete response [CR] + partial response [PR] +
stable disease lasting ≥ 12 weeks as defined by RECIST criteria) of pazopanib
hydrochloride with vs without pemetrexed disodium in patients with stage IIIB/IV
non-squamous non-small cell lung cancer who progressed on first-line therapy containing
bevacizumab as defined by RECIST criteria.

Secondary

- To estimate the combined response rate (CR + PR) in these patients according to RECIST
criteria.

- To estimate the progression-free survival and overall survival of these patients.

- To evaluate the safety and tolerability of treatment using the NCI CTCAE version 4.0.

- To explore potential correlations between blood biomarkers and clinical benefit.

OUTLINE: This is a multicenter study. Patients who have been treated with prior pemetrexed
disodium are assigned to group 1 and patients who have not been treated with pemetrexed
disodium are assigned to group 2.

- Group 1 (pazopanib hydrochloride alone): Patients receive oral pazopanib hydrochloride
on days 1-21. Courses repeat every 21 days in the absence of disease progression or
unacceptable toxicity.

- Group 2 (pazopanib hydrochloride and pemetrexed disodium): Patients receive oral
pazopanib hydrochloride on days 1-21 and pemetrexed disodium IV over 10 minutes on day
1. Courses repeat every 21 days in the absence of disease progression or unacceptable
toxicity.

Blood samples are collected periodically for biomarker analysis.

After completion of study therapy, patients are followed up every 2 months for 2 years.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Cytologically or histologically confirmed stage IIIB (with malignant pleural or
pericardial effusion or supraclavicular lymph node involvement) or stage IV non-small
cell lung cancer

- Non-squamous histology

- Measurable disease using RECIST criteria

- Evidence of progression while on bevacizumab (documentation of radiographic
progression must be ≤ 8 weeks from last bevacizumab treatment)

- No lesions infiltrating major pulmonary vessels

- No significant uncontrolled pleural effusion, ascites, or other clinically
significant third space fluid collections

- No spinal cord compression, leptomeningeal carcinomatosis, or symptomatic and/or
untreated CNS metastasis

- Patients who were treated for CNS metastases are eligible provided they are
asymptomatic and have had no requirement for steroids within the past 2 weeks

- Anticonvulsants that have minimal drug interaction potential (i.e., levatiracem)
are allowed provided the patient has been on a stable dose for ≥ 4 weeks

- Screening with CNS imaging studies (CT scan or MRI) is required if clinically
indicated or if the patient has a history of CNS metastases

PATIENT CHARACTERISTICS:

- ECOG performance status 0-2

- ANC ≥ 1,500/mm^3

- Hemoglobin ≥ 9 g/dL (5.6 mmol/L) (no transfusion within the past 7 days)

- Platelet count ≥ 100,000/mm^3

- PT or INR ≤ 1.5 times upper limit of normal (ULN)

- PTT ≤ 1.5 times ULN

- Total bilirubin ≤ 1.5 times ULN*

- AST and ALT ≤ 2.5 times ULN*

- Serum creatinine ≤ 1.5 mg/dL (133 μmol/L) OR calculated creatinine clearance ≥ 45
mL/min

- Urine protein to creatinine ratio < 1 OR < 1 g protein on 24-hour urine collection

- Corrected QT interval ≤ 480 msec

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Willing to provide blood samples for biomarker analysis

- Able to swallow and retain oral medication

- No clinically significant gastrointestinal (GI) abnormalities that may increase the
risk for GI bleeding including, but not limited to, any of the following:

- Active peptic ulcer disease

- Known intraluminal metastatic lesion(s) with risk of bleeding

- Active inflammatory bowel disease (e.g., ulcerative colitis, Crohn disease) or
other GI conditions with increased risk of perforation

- History of abdominal fistula, GI perforation, or intra-abdominal abscess within
the past 28 days

- No clinically significant GI abnormalities that may affect absorption of the study
drugs including, but not limited to, any of the following:

- Malabsorption syndrome

- Major resection of the stomach or small bowel

- No history of GI bleeding within the past 6 months

- No prior malignancy except for completely resected nonmelanomatous skin carcinoma or
successfully treated in situ carcinoma unless the patient has been disease-free for ≥
3 years

- No uncontrolled infection or nonhealing wound, fracture, or ulcer

- No history of any one or more of the following cardiovascular conditions within the
past 6 months:

- Cardiac angioplasty or stenting

- Myocardial infarction

- Unstable angina

- Coronary artery bypass graft surgery

- Symptomatic peripheral vascular disease

- NYHA class III or IV congestive heart failure

- No poorly controlled hypertension (defined as systolic BP ≥ 140 mm Hg or diastolic BP
≥ 90 mm Hg)

- Initiation or adjustment of antihypertensive medication(s) is allowed before
study entry

- No history of cerebrovascular accident including transient ischemic attack, pulmonary
embolism, or untreated deep venous thrombosis (DVT) within the past 6 months

- Patients with recent DVT who have been treated with therapeutic anticoagulating
agents for ≥ 6 weeks are eligible provided they are monitored regularly for
changes in relevant coagulation parameters, as clinically indicated, as well as
any clinical bleeding episodes

- No major trauma within the past 28 days

- No evidence of active bleeding or bleeding diathesis

- No hemoptysis within the past 6 weeks

- No serious and/or unstable pre-existing medical, psychiatric, or other condition that
could interfere with the patient's safety, provision of informed consent, or
compliance to study procedures NOTE: *No concurrent elevations in bilirubin and
AST/ALT above 1.0 times ULN

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- No more than 1 prior cytotoxic chemotherapy regimen (platinum-containing) in
combination with bevacizumab

- Bevacizumab continued as a single agent after completion of cytotoxic therapy in
the first-line setting does not constitute a second regimen and is therefore
allowed

- If one or more of the agents in the patient's regimen had to be reduced,
omitted, or substituted with another similar drug due to toxicity, these changes
do not constitute a new regimen

- Last bevacizumab treatment must be within the past 3-9 weeks

- No prior exposure to anti-VEGF therapy except for bevacizumab

- No ongoing toxicity from prior anticancer therapy that is > grade 1 or baseline
and/or that is progressing in severity (except for alopecia)

- More than 28 days since prior major surgery (procedures such as catheter placement
are not considered to be major)

- More than 14 days since prior radiotherapy, surgery, or tumor embolization

- More than 14 days or 5 half-lives (whichever is longer) since prior chemotherapy,
immunotherapy, biologic therapy, investigational therapy, or hormonal therapy

- More than 14 days since prior steroids

- Patients with a creatinine clearance of 45-79 mL/min who are otherwise eligible for
treatment in group 2 but are on daily treatment with NSAIDs are not eligible unless
they can interrupt NSAIDs with short-elimination half-lives 2 days before (5 days for
NSAIDs with longer half-lives), the day of, and 2 days after administration of
pemetrexed disodium

- At least 14 days since prior and no concurrent medications (substrates of CYP3A4,
CYP2C8, and CYP2D6) with a narrow therapeutic window

- These medications may be resumed 7-15 days after the last dose of pazopanib
hydrochloride

- No concurrent strong CYP3A4 inhibitors

- No concurrent CYP3A4 inducers

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Disease-control rate

Safety Issue:

No

Principal Investigator

Honey Strickland

Investigator Affiliation:

UNC Lineberger Comprehensive Cancer Center

Authority:

Unspecified

Study ID:

CDR0000670857

NCT ID:

NCT01107652

Start Date:

December 2010

Completion Date:

Related Keywords:

  • Lung Cancer
  • stage IIIB non-small cell lung cancer
  • stage IV non-small cell lung cancer
  • adenocarcinoma of the lung
  • bronchoalveolar cell lung cancer
  • large cell lung cancer
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms

Name

Location

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel HillChapel Hill, North Carolina  27599-7570