Topotecan and Bevacizumab in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer That Did Not Respond to Previous Systemic Chemotherapy

NCT00365547 | Completed Phase 2 Results DMC

• 2 other identifiers: 2005LS083UMN-0602M81427
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 2

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as topotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as Avastin (bevacizumab), can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving topotecan together with bevacizumab may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving topotecan together with bevacizumab works in treating patients with stage IIIB or stage IV non-small cell lung cancer that did not respond to previous systemic chemotherapy.

Conditions

Lung Cancer

Keywords

recurrent non-small cell 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

Outcome Measures

Primary Outcomes (1)

• Median Time to Disease Progression

  Assessed by Response Evaluation Criteria In Solid Tumor (RECIST criteria). Progression is defined as a measureable increase in the smallest dimension of any target or non-target lesion, or the appearance of new lesions since baseline.

  From Day 1 Until First Documented Disease Progression or Date of Death (Whichever Occurred First)

Secondary Outcomes (4)

• Number of Tumor Responders

  From Day 1 Until Disease Progression or Date of Death (Whichever Occurred First), Up to 1 Year

• Median Time to Response

  From Day 1 Until Tumor Response

• Median Duration of Response

  Day of 1st Response Until Disease Progression of Death/Last Contact

• Median Overall Survival

  From Day 1 Until Death Occurred

Study Arms (1)

Patients Treated With Topotecan and Avastin in NSCLC

EXPERIMENTAL

Weekly topotecan hydrochloride and bi-weekly Avastin (bevacizumab) in patients with non-small cell lung cancer (NSCLC) who have failed prior systemic chemotherapy.

Biological: bevacizumab; Drug: topotecan hydrochloride

Interventions

bevacizumab BIOLOGICAL

Will be given by intravenous (IV) infusion at the dose of 10 mg/kg on days 1 and 15 after topotecan administration until disease progression or for another reason.

Also known as: Avastin

Patients Treated With Topotecan and Avastin in NSCLC

topotecan hydrochloride DRUG

Topotecan 4 mg/m\^2 intravenously (IV) will be given as a 30-minute intravenous infusion on days 1, 8, and 15 with a rest on day 22. Treatment will be repeated every 28 days until disease progression or for another reason.

Also known as: Hycamtin(TM)

Patients Treated With Topotecan and Avastin in NSCLC

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically or cytologically confirmed non-small cell lung cancer (NSCLC). Patients with extrathoracic-only squamous cell NSCLC are eligible. Intrathoracic squamous cell carcinoma will not be eligible. Mixed tumors will be categorized by the predominant cell type unless small cell elements are present, in which case the patient is ineligible.
• Disease that has failed one or more prior standard therapy and is no longer likely to respond to such therapy.
• Prior systemic chemotherapy, immunotherapy, or biological therapy is allowed, except for prior use of Avastin and topotecan in combination. Patient must be at least 14 days from previous radiation or systemic therapy (at least 30 days for investigational agents) and have recovered from the acute toxic effects of the treatment prior to study enrollment.
• Disease status must be measurable or evaluable as defined by Response Evaluation Criteria In Solid Tumors (RECIST criteria)
• Eastern Cooperative Oncology Group (ECOG) Performance status of 0 or 1
• Age 18 years or greater
• Adequate organ function within 14 days of study registration including the following:
• Adequate bone marrow reserve:
• absolute neutrophil count (ANC) \> or = to 1.5 x 10\^9/L,
• platelets \>100 x 10\^9/L,
• hemoglobin \> 9 g/dL
• Hepatic:
• bilirubin \<1.5 times the upper limit of normal (x ULN),
• alkaline phosphatase (ALP), aspartate transaminase (AST) and alanine transaminase (ALT) \<3.0 x ULN (ALP, AST, and ALT \<5 x ULN is acceptable if liver has tumor involvement)
• Renal:

You may not qualify if:

• Pregnant (positive pregnancy test) or breast-feeding. Topotecan is pregnancy category D - clear evidence of risk in pregnancy; Avastin is pregnancy category C - risk in pregnancy cannot be ruled out. Pregnancy testing is not required for post-menopausal or surgically sterilized women
• Known hypersensitivity to any component of Avastin (bevacizumab)
• Inadequately controlled hypertension (defined as systolic blood pressure \> 150 and/or diastolic blood pressure \> 100 mmHg)
• Any prior history of hypertensive crisis or hypertensive encephalopathy
• New York Heart Association (NYHA) Grade II or greater congestive heart failure
• History of myocardial infarction or unstable angina within 6 months prior to Day 1
• History of stroke or transient ischemic attack within 6 months prior to Day 1
• Known central nervous system (CNS) disease, except for treated brain metastasis. Treated brain metastases are defined as having no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period. Anticonvulsants (stable dose) are allowed. Treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS; Gamma Knife, LINAC, or equivalent) or a combination as deemed appropriate by the treating physician. Patients with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to Day 1 will be excluded
• Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1
• History of hemoptysis (≥ ½ teaspoon of bright red blood per episode) within 1 month prior to Day 1
• Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
• Active malignancy other than non-small cell lung cancer (NSCLC), treated superficial basal cell and superficial squamous (skin) cell, or carcinoma in situ of the cervix within last five years are allowed.
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 or anticipation of need for major surgical procedure during the course of the study
• Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 1

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead

Study Sites (2)

Masonic Cancer Center at University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Park Nicollet Cancer Center

Saint Louis Park, Minnesota, 55416, United States

Location

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Adenocarcinoma of Lung; Adenocarcinoma, Bronchiolo-Alveolar

Interventions

Bevacizumab; Topotecan

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Camptothecin; Alkaloids; Heterocyclic Compounds

Results Point of Contact

• Title: Arkadiusz Dudek, M.D.
• Organization: Masonic Cancer Center, University of Minnesota

dudek002@umn.edu

612-624-0123

Study Officials

• Arkadiusz Dudek, MD

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 16, 2006
• First Posted: August 17, 2006
• Study Start: September 1, 2006
• Primary Completion: September 1, 2011
• Study Completion: September 1, 2011
• Last Updated: December 28, 2017
• Results First Posted: June 15, 2012

Record last verified: 2017-12

Locations

US (2)