Ph II of Vinflunine and Cetuximab in Second Line Treatment of NSCLC

• Sponsor: UNC Lineberger Comprehensive Cancer Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00519831
• Collaborator: Bristol-Myers Squibb (Industry)
• Enrollment: 18
• Locations: 2
• Arm: 1
• Duration (Months): 27
• Patients Per Site: 9
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as vinflunine, 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 cetuximab, can block tumor growth in different ways. Some find tumor cells and help kill them or carry tumor-killing substances to them. Others interfere with the ability of tumor cells to grow and spread. Giving vinflunine together with cetuximab may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving vinflunine together with cetuximab works as second-line therapy in treating patients with stage IIIB or stage IV non-small cell lung cancer.

Condition or Disease	Intervention/Treatment	Phase
Lung Cancer	Biological: cetuximab; Drug: vinflunine	Phase 2

Detailed Description

OBJECTIVES:

Primary

• Estimate the objective response rate in patients receiving vinflunine and cetuximab as second-line therapy for stage IIIB or IV non-small cell lung cancer.

Secondary

• Determine the progression-free survival of patients treated with this regimen.

• Determine the safety of this regimen in these patients.

• Determine the overall survival of patients treated with this regimen.

• Determine the duration of overall response in these patients.

OUTLINE: This is a multicenter study.

Patients receive vinflunine IV over 15-20 minutes on day 1 and cetuximab IV over 60-120 minutes on days 1, 8, and 15. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients with responding disease may receive additional courses beyond 4 courses at the discretion of the principal investigator.

After completion of study therapy, patients are followed periodically for 6 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Vinflunine and Cetuximab in the Second Line Treatment of Stage IIIB/IV Non-Small Cell Lung Cancer
• Study Start Date: Aug 1, 2007
• Actual Primary Completion Date: Feb 1, 2008
• Actual Study Completion Date: Nov 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Vinflunine + Cetuximab Patients may receive more than 4 cycles of therapy if they continue to demonstrate response to therapy, have limited toxicity, and if the treating physician determines that they are deriving clinical benefit from the treatment. The decision of continuing therapy beyond 4 cycles must be discussed with the principal investigator.	Biological: cetuximab; 400 mg/m² week 1,then 250 mg/m² weekly; Other Names: erbitux ; Drug: vinflunine; Vinflunine 320 mg/m² every 21 days; Other Names: Javlor

Outcome Measures

Primary Outcome Measures

1. Overall Tumor Response Rate as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Criteria. Sum of Partial Responses (PR) and Complete Responses (CR). [Baseline, after cycle 2, within 2 weeks of completing cycle 4]

   Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions. Measurable lesions must be accurately measured in at least one dimension (longest diameter to be recorded) as > 20 mm with conventional techniques or as > 10mm with spiral CT scan or nonmeasurable, but evaluable. Evaluable is nonmeasurable disease that includes ascites, malignant pleural/pericardial effusion, bone lesions, or marrow involvement.

Secondary Outcome Measures

1. Duration of Response [After cycle 4]

2. Overall Survival [Every 30 days]

3. Progression-free Survival [after cycle 2, within 2 weeks of completing cycle 4]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed non-small cell lung cancer (NSCLC) meeting 1 of the following criteria:

• Unresectable stage IIIB disease with pleural effusion or pericardial effusion

• Stage IIIB disease that was treated with chemotherapy alone as first-line therapy

• Stage IV disease

• Must have documented progression of disease after receiving one cytotoxic chemotherapy regimen for metastatic disease

• At least one lesion that is bidimensionally measurable by CT scan or MRI

• Must have evaluable disease outside the radiation field

• New lesions that develop within the radiation field are allowed

• Measurable disease status as defined by RECIST criteria

• Brain metastases allowed provided they have been previously treated and are controlled

PATIENT CHARACTERISTICS:

Inclusion criteria:

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2

• Absolute neutrophil count (ANC) > 1,000/mm³

• Hemoglobin > 8.0 g/dL

• Platelet count > 75,000/mm³

• Creatinine < 2.0 times upper limit of normal (ULN)

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 5 times ULN

• Total bilirubin < 2.5 times ULN

• Prior malignancy allowed provided the patient's life expectancy is best defined by the diagnosis of NSCLC

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for up to 4 weeks after completion of study therapy

Exclusion criteria:

• Peripheral neuropathy ≥ 2

• Severe allergic reaction to prior vinca alkaloid treatment

• Active or uncontrolled infection

• Significant history of uncontrolled cardiac disease, including any of the following:

• Uncontrolled hypertension

• Unstable angina

• Myocardial infarction within the past 6 months

• Uncontrolled congestive heart failure

• Cardiomyopathy with decreased ejection fraction

• Severe reaction to prior monoclonal antibody therapy

PRIOR CONCURRENT THERAPY:

Inclusion criteria:

• See Disease Characteristics

• Prior oral tyrosine kinase inhibitor therapy (e.g. gefitinib or erlotinib) allowed

• Not considered cytotoxic therapy for study eligibility purposes if given alone as first-line therapy

• At least 1 week since prior radiotherapy

• At least 21 days since prior and no other concurrent chemotherapy

• Prior adjuvant therapy allowed provided patient received one cytotoxic chemotherapy regimen as treatment for metastatic disease

• Prior bevacizumab allowed

Exclusion criteria:

• Two or more cytotoxic chemotherapy regimens as treatment for metastatic disease

• Prior therapy with monoclonal antibody directed at the epidermal growth factor receptor (EGFR) pathway

• Prior therapy with a vinca alkaloid in the metastatic setting

• Concurrent bevacizumab

• Other concurrent investigational agent(s)

• Concurrent colony-stimulating factors as primary prophylaxis for the prevention of febrile neutropenia

• Concurrent CYP3A4 inhibitor(s)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alamance Oncology/Hematology Associates, LLP	Burlington	North Carolina	United States	27216
2	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina	United States	27599-7295

Sponsors and Collaborators

• UNC Lineberger Comprehensive Cancer Center
• Bristol-Myers Squibb

Investigators

• Principal Investigator: Thomas E. Stinchcombe, MD, UNC Lineberger Comprehensive Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: UNC Lineberger Comprehensive Cancer Center
• ClinicalTrials.gov Identifier: NCT00519831
• Other Study ID Numbers: UNC LCCC 0503; NCT00330031
• First Posted: Aug 23, 2007
• Last Update Posted: Jun 9, 2017
• Last Verified: May 1, 2017

• Keywords provided by UNC Lineberger Comprehensive Cancer Center: stage IIIB non-small cell lung cancer; stage IV non-small cell lung cancer; recurrent non-small cell lung cancer
• Additional relevant MeSH terms: Lung Neoplasms; Cetuximab

Study Results

Participant Flow

Pre-assignment Detail	18 patients were enrolled, 2 patients were consented but not enrolled. 1 patient withdrew and 1 patient was taken off the study due to decline in performance status.

Arm/Group Title	Vinflunine + Cetuximab
Arm/Group Description	Patients may receive more than 4 cycles of therapy if they continue to demonstrate response to therapy, have limited toxicity, and if the treating physician determines that they are deriving clinical benefit from the treatment. The decision of continuing therapy beyond 4 cycles must be discussed with the principal investigator. cetuximab: 400 mg/m² week 1,then 250 mg/m² weekly vinflunine: Vinflunine 320 mg/m² every 21 days
Period Title: Overall Study
STARTED	16
COMPLETED	13
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Vinflunine + Cetuximab
Arm/Group Description	Patients may receive more than 4 cycles of therapy if they continue to demonstrate response to therapy, have limited toxicity, and if the treating physician determines that they are deriving clinical benefit from the treatment. The decision of continuing therapy beyond 4 cycles must be discussed with the principal investigator. cetuximab: 400 mg/m² week 1,then 250 mg/m² weekly vinflunine: Vinflunine 320 mg/m² every 21 days
Overall Participants	16
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	60.5
Sex: Female, Male (Count of Participants)
Female	7 43.8%
Male	9 56.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 6.3%
White	15 93.8%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	16 100%
Number of Participants who had a score of 0-1 in the The Eastern Cooperative Oncology Group (ECOG) (Count of Participants)
Count of Participants [Participants]	16 100%

Outcome Measures

1. Primary Outcome

Title	Overall Tumor Response Rate as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Criteria. Sum of Partial Responses (PR) and Complete Responses (CR).
Description	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions. Measurable lesions must be accurately measured in at least one dimension (longest diameter to be recorded) as > 20 mm with conventional techniques or as > 10mm with spiral CT scan or nonmeasurable, but evaluable. Evaluable is nonmeasurable disease that includes ascites, malignant pleural/pericardial effusion, bone lesions, or marrow involvement.
Time Frame	Baseline, after cycle 2, within 2 weeks of completing cycle 4

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vinflunine + Cetuximab
Arm/Group Description	Patients may receive more than 4 cycles of therapy if they continue to demonstrate response to therapy, have limited toxicity, and if the treating physician determines that they are deriving clinical benefit from the treatment. The decision of continuing therapy beyond 4 cycles must be discussed with the principal investigator. cetuximab: 400 mg/m² week 1,then 250 mg/m² weekly vinflunine: Vinflunine 320 mg/m² every 21 days
Measure Participants	13
Count of Participants [Participants]	3 18.8%

2. Secondary Outcome

Title	Duration of Response
Time Frame	After cycle 4

Outcome Measure Data

Analysis Population Description

Data not collected due to early study termination.

Arm/Group Title	Vinflunine + Cetuximab
Arm/Group Description	Patients may receive more than 4 cycles of therapy if they continue to demonstrate response to therapy, have limited toxicity, and if the treating physician determines that they are deriving clinical benefit from the treatment. The decision of continuing therapy beyond 4 cycles must be discussed with the principal investigator. cetuximab: 400 mg/m² week 1,then 250 mg/m² weekly vinflunine: Vinflunine 320 mg/m² every 21 days
Measure Participants	0

3. Secondary Outcome

Title	Overall Survival
Time Frame	Every 30 days

Outcome Measure Data

Analysis Population Description

Data not collected due to early study termination.

Arm/Group Title	Vinflunine + Cetuximab
Arm/Group Description	Patients may receive more than 4 cycles of therapy if they continue to demonstrate response to therapy, have limited toxicity, and if the treating physician determines that they are deriving clinical benefit from the treatment. The decision of continuing therapy beyond 4 cycles must be discussed with the principal investigator. cetuximab: 400 mg/m² week 1,then 250 mg/m² weekly vinflunine: Vinflunine 320 mg/m² every 21 days
Measure Participants	0

4. Secondary Outcome

Title	Progression-free Survival
Time Frame	after cycle 2, within 2 weeks of completing cycle 4

Outcome Measure Data

Analysis Population Description

Data not collected due to early study termination.

Arm/Group Title	Vinflunine + Cetuximab
Arm/Group Description	Patients may receive more than 4 cycles of therapy if they continue to demonstrate response to therapy, have limited toxicity, and if the treating physician determines that they are deriving clinical benefit from the treatment. The decision of continuing therapy beyond 4 cycles must be discussed with the principal investigator. cetuximab: 400 mg/m² week 1,then 250 mg/m² weekly vinflunine: Vinflunine 320 mg/m² every 21 days
Measure Participants	0

Adverse Events

Time Frame	Patients were followed until disease progression, death, or six months after completion of treatment.
Arm/Group Title	Vinflunine + Cetuximab
Arm/Group Description	Patients may receive more than 4 cycles of therapy if they continue to demonstrate response to therapy, have limited toxicity, and if the treating physician determines that they are deriving clinical benefit from the treatment. The decision of continuing therapy beyond 4 cycles must be discussed with the principal investigator. cetuximab: 400 mg/m² week 1,then 250 mg/m² weekly vinflunine: Vinflunine 320 mg/m² every 21 days
All Cause Mortality
	Vinflunine + Cetuximab
	Affected / at Risk (%)	# Events
Total	6/16 (37.5%)
Serious Adverse Events
	Vinflunine + Cetuximab
	Affected / at Risk (%)	# Events
Total	8/16 (50%)
Gastrointestinal disorders
Constipation	2/16 (12.5%)
Ileus, GI (functional obstruction of bowel, i.e., neuroconstipation)	1/16 (6.3%)
Nausea	1/16 (6.3%)
Vomiting	1/16 (6.3%)
Immune system disorders
Allergic reaction/hypersensitivity (including drug fever)	2/16 (12.5%)
Infections and infestations
Infection - Lung	1/16 (6.3%)
Injury, poisoning and procedural complications
Thrombosis/embolism (vascular access-related)	1/16 (6.3%)
Investigations
Neutrophils/granulocytes (ANC/AGC)	1/16 (6.3%)
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)	1/16 (6.3%)
Other (Not Including Serious) Adverse Events
	Vinflunine + Cetuximab
	Affected / at Risk (%)	# Events
Total	15/16 (93.8%)
Eye disorders
Dry eye syndrome	1/16 (6.3%)
Ocular/Visual - Other (Specify, __)	2/16 (12.5%)
Ophthalmoplegia/diplopia (double vision)	1/16 (6.3%)
Gastrointestinal disorders
Constipation	5/16 (31.3%)
Diarrhea	1/16 (6.3%)
Mucositis/stomatitis (clinical exam) - Oral cavity	1/16 (6.3%)
Nausea	4/16 (25%)
Pain - Abdomen NOS	3/16 (18.8%)
Vomiting	3/16 (18.8%)
General disorders
Fatigue (asthenia, lethargy, malaise)	4/16 (25%)
Pain - Chest/thorax NOS	1/16 (6.3%)
Pain - Other (Specify, __)	1/16 (6.3%)
Pain - Pain NOS	5/16 (31.3%)
Immune system disorders
Allergic reaction/hypersensitivity (including drug fever)	1/16 (6.3%)
Injury, poisoning and procedural complications
Rash: dermatitis associated with radiation - Chemoradiation	1/16 (6.3%)
Thrombosis/embolism (vascular access-related)	1/16 (6.3%)
Investigations
Creatinine	1/16 (6.3%)
Leukocytes (total WBC)	1/16 (6.3%)
Neutrophils/granulocytes (ANC/AGC)	11/16 (68.8%)
Platelets	1/16 (6.3%)
Metabolism and nutrition disorders
Anorexia	1/16 (6.3%)
Magnesium, serum-low (hypomagnesemia)	2/16 (12.5%)
Metabolic/Laboratory - Other (Specify, __)	1/16 (6.3%)
Potassium, serum-low (hypokalemia)	1/16 (6.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pain - Tumor pain	1/16 (6.3%)
Nervous system disorders
Tremor	1/16 (6.3%)
Vasovagal episode	1/16 (6.3%)
Psychiatric disorders
Mood alteration - Anxiety	2/16 (12.5%)
Respiratory, thoracic and mediastinal disorders
Cough	3/16 (18.8%)
Dyspnea (shortness of breath)	3/16 (18.8%)
Hemorrhage, pulmonary/upper respiratory - Bronchopulmonary NOS	2/16 (12.5%)
Hemorrhage, pulmonary/upper respiratory - Nose	1/16 (6.3%)
Hemorrhage, pulmonary/upper respiratory - Respiratory tract NOS	1/16 (6.3%)
Pain - Throat/pharynx/larynx	1/16 (6.3%)
Pulmonary/Upper Respiratory - Other (Specify, __)	1/16 (6.3%)
Pulmonary/Upper Respiratory - Other (Specify, __)	1/16 (6.3%)
Skin and subcutaneous tissue disorders
Dry skin	2/16 (12.5%)
Hair loss/alopecia (scalp or body)	3/16 (18.8%)
Nail changes	1/16 (6.3%)
Rash/desquamation	6/16 (37.5%)
Rash: hand-foot skin reaction	1/16 (6.3%)
Sweating (diaphoresis)	1/16 (6.3%)
Ulceration	1/16 (6.3%)

Limitations/Caveats

Study was terminated early due to unavailable drug/funding. Preliminary analysis reported.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.