Paclitaxel, Bevacizumab and Pemetrexed in Patients With Untreated, Advanced Non-Small Cell Lung Cancer Using Web-Based Data Collection, Patient Self-Reporting of Adverse Effects and Automated Response Assessment

• Sponsor: Memorial Sloan Kettering Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00807573
• Collaborator: (none)
• Enrollment: 44
• Locations: 5
• Arm: 1
• Duration (Months): 64
• Patients Per Site: 8.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the percentage of patients with non-small cell lung cancer that will experience a shrinkage of their tumors following treatment with three medications given together: paclitaxel, pemetrexed (Alimta®), and bevacizumab (Avastin®). Each of these medications has been approved by the FDA for patients that have not received any treatment for their lung cancer. This study is designed to study the effects of all three drugs given at the same time.

Each of these medications has been studied in lung cancer and is commercially available. Paclitaxel and pemetrexed are traditional chemotherapy drugs. Bevacizumab is a monoclonal antibody, which means that it attaches to a specific target. Bevacizumab attaches to a protein in the blood stream called Vascular Endothelial GrowthFactor (VEGF). VEGF helps tumors grow new blood vessels to feed themselves, and bevacizumab is thought to help block this new growth of blood vessels and starve the tumors of the nutrients they need.

Condition or Disease	Intervention/Treatment	Phase
Lung Cancer	Drug: Paclitaxel; Drug: Pemetrexed; Drug: Bevacizumab	Phase 2

Detailed Description

In this clinical trial, we also will be studying other things. We want to learn more about how to manage side effects patients may develop during chemotherapy. Cancer patients may develop side effects during treatment, such as nausea, pain, fatigue, diarrhea, constipation, or shortness of breath. These symptoms may be due to the cancer itself, or due to treatments like chemotherapy drugs or radiation therapy. Doctors and nurses often ask patients about their symptoms, because an important part of cancer treatment is to make patients feel as well as possible. If patients do not feel well, we may need to change the way we are treating them or prescribe therapies that will decrease their symptoms. The best way to find out how the patient is feeling is to ask them directly.

We are interested in developing new ways to ask patients about how they are feeling, using the Internet. A special new website called STAR ("Symptom Tracking and Reporting for Patients") has been developed to help patients record this information, so that their doctors and nurses can review it during clinic appointments. This study is designed to help us see if STAR is a helpful way for us to keep track of information about patients' symptoms and quality of life.

As part of this study, a computerized (automated) technique of determining the size of the patients tumor(s) before and after treatment will be used. This has been tested in the past and found to be more accurate. The automated technique of determining tumor size will be used with the routine CT scans that the patient will have as part of the study. This automated method of measuring the tumor(s) will allow us to know sooner whether this drug treatment is causing the disease to shrink.

The information from STAR and the automated tumor measurements are going to be placed on a very secure Internet site. This will provide the doctor with all of the information needed to determine if this drug combination is working for the patient and whether to continue this study.

Also, if there is a tumor sample from a biopsy done in the past, it will be analyzed for a protein that may be present in the lung cancer.

Study Design

• Study Type: Interventional
• Actual Enrollment: 44 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of Paclitaxel, Bevacizumab and Pemetrexed in Patients With Untreated, Advanced Non-Small Cell Lung Cancer Using Web-Based Data Collection, Patient Self-Reporting of Adverse Effects and Automated Response Assessment
• Study Start Date: Dec 1, 2008
• Actual Primary Completion Date: Apr 1, 2014
• Actual Study Completion Date: Apr 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Paclitaxel, Bevacizumab & Pemetrexed During each 28-day cycle, paclitaxel, pemetrexed and bevacizumab will be given intravenously on days 1 and 15. Paclitaxel will be administered at 90mg/m^2 over 60 minutes on days 1 and 15. Pemetrexed 500mg/m^2 will be administered over 10 minutes on days 1 and 15. Bevacizumab will be given at 10mg/kg over 20 minutes on days 1 and 15	Drug: Paclitaxel; Day 1: Paclitaxel (90 mg/m^2 over 60 minutes) Day 15: Paclitaxel (90 mg/m^2 over 60 minutes); Drug: Pemetrexed; Day 1: Pemetrexed (500 mg/m^2 over 10 minutes) Day 15 Pemetrexed (500 mg/m2 over 10 minutes); Drug: Bevacizumab; Day 1:Bevacizumab (10 mg/kg over 20 minutes) Day 15: Bevacizumab (10 mg/kg over 20 minutes)

Outcome Measures

Primary Outcome Measures

1. Objective Response Rate (CR + PR by RECIST) Paclitaxel, Pemetrexed, and Bevacizumab in Patients With Advanced Non-Small Lung Cancer Who Have Received no Prior Treatment for Metastatic Disease. [2 years]

   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; Overall Response (OR) = CR + PR.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Pathologically confirmed Non-Small Cell Lung Cancer at MSKCC

• Clinical stage IIIB or IV.

• Measurable disease as per RECIST

• Greater than 6 months since receiving neo-adjuvant or adjuvant chemotherapy for Non-Small Cell Lung Cancer.

• Age ≥ 18 years.

• Karnofsky performance status of ≥ to 70.

• Marrow and organ function as follows:

• WBC ≥ to 4000/mm3

• Platelets ≥ to 160,000

• Bilirubin ≤ to 1.2mg/dL

• Creatinine clearance ≥ to 40mL/min

• AST and/or /ALT ≤ 37 Units/L (if one of these elevated, must be ≤ 2.5 ULN)

• Systolic blood pressure ≤ to 150mmHg or diastolic blood pressure ≤ to 100 mmHg).

• The subject is able to read and comprehend English text from a computer screen.

• Women of childbearing potential and sexually active men enrolled in the study must agree to practice effective contraception.

Exclusion Criteria:

• Squamous cell carcinoma.

• Prior treatment with paclitaxel, pemetrexed or bevacizumab for NSCLC.

• Prior systemic anticancer therapy for advanced NSCLC.

• Symptomatic brain metastases with evidence of hemorrhage.

• Radiation therapy to greater than 25% of the bone marrow within 30 days of starting treatment.

• Peripheral neuropathy greater than grade 1.

• Malignancies within the past 5 years other than non-melanoma skin cancer.

• Patients with other serious medical illnesses including, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements.

• History of hemoptysis.

• History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess.

• History of myocardial infarction or stroke within 6 months prior to enrollment.

• Pregnancy or lactation.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan-Kettering at Basking Ridge	Basking Ridge	New Jersey	United States	07920
2	Memorial Sloan-Kettering Cancer Center @ Suffolk	Commack	New York	United States	11725
3	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10065
4	Memorial Sloan-Kettering at Mercy Medical Center	Rockville Centre	New York	United States
5	Memoral Sloan Kettering Cancer Center@Phelps Memorial Hospital	Sleepy Hollow	New York	United States

Sponsors and Collaborators

• Memorial Sloan Kettering Cancer Center

Investigators

• Principal Investigator: Maria Pietanza, MD, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Memorial Sloan-Kettering Cancer Center

Publications

None provided.

• Responsible Party: Memorial Sloan Kettering Cancer Center
• ClinicalTrials.gov Identifier: NCT00807573
• Other Study ID Numbers: 08-109
• First Posted: Dec 12, 2008
• Last Update Posted: Dec 30, 2015
• Last Verified: Nov 1, 2015

• Keywords provided by Memorial Sloan Kettering Cancer Center: BEVACIZUMAB (AVASTIN); PEMETREXED (ALTIMA); TAXOL (PACLITAXEL); 08-109
• Additional relevant MeSH terms: Lung Neoplasms; Paclitaxel; Bevacizumab; Pemetrexed

Study Results

Participant Flow

Arm/Group Title	Paclitaxel, Bevacizumab & Pemetrexed
Arm/Group Description	Paclitaxel, Bevacizumab and Pemetrexed in Untreated, Advanced Non-Small Cell Lung Cancer. During each 28-day cycle, paclitaxel, pemetrexed and bevacizumab will be given intravenously on days 1 and 15. Paclitaxel will be administered at 90mg/m^2 over 60 minutes on days 1 and 15. Pemetrexed 500mg/m^2 will be administered over 10 minutes on days 1 and 15. Bevacizumab will be given at 10mg/kg over 20 minutes on days 1 and 15, and 19.
Period Title: Overall Study
STARTED	44
COMPLETED	42
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Paclitaxel, Bevacizumab & Pemetrexed
Arm/Group Description	Paclitaxel, Bevacizumab and Pemetrexed in Untreated, Advanced NSCLC. During each 28-day cycle, paclitaxel, pemetrexed and bevacizumab will be given intravenously on days 1 and 15. Paclitaxel will be administered at 90mg/m2 over 60 minutes on days 1 and 15. Pemetrexed 500mg/m2 will be administered over 10 minutes on days 1 and 15. Bevacizumab will be given at 10mg/kg over 20 minutes on days 1, 15 and 19.
Overall Participants	44
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	28 63.6%
>=65 years	16 36.4%
Sex: Female, Male (Count of Participants)
Female	22 50%
Male	22 50%
Region of Enrollment (participants) [Number]
United States	44 100%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate (CR + PR by RECIST) Paclitaxel, Pemetrexed, and Bevacizumab in Patients With Advanced Non-Small Lung Cancer Who Have Received no Prior Treatment for Metastatic Disease.
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; Overall Response (OR) = CR + PR.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Paclitaxel, Bevacizumab & Pemetrexed
Arm/Group Description	Paclitaxel, Bevacizumab and Pemetrexed in Untreated, Advanced Non-Small Cell Lung Cancer. During each 28-day cycle, paclitaxel, pemetrexed and bevacizumab will be given intravenously on days 1 and 15. Paclitaxel will be administered at 90mg/m^2 over 60 minutes on days 1 and 15. Pemetrexed 500mg/m^2 will be administered over 10 minutes on days 1 and 15. Bevacizumab will be given at 10mg/kg over 20 minutes on days 1 and 15, and 19.
Measure Participants	42
Partial Response	27 61.4%
Stable Disease	15 34.1%

Adverse Events

Arm/Group Title	Paclitaxel, Bevacizumab & Pemetrexed
Arm/Group Description	Paclitaxel, Bevacizumab and Pemetrexed in Untreated, Advanced Non-Small Cell Lung Cancer. During each 28-day cycle, paclitaxel, pemetrexed and bevacizumab will be given intravenously on days 1 and 15. Paclitaxel will be administered at 90mg/m^2 over 60 minutes on days 1 and 15. Pemetrexed 500mg/m^2 will be administered over 10 minutes on days 1 and 15. Bevacizumab will be given at 10mg/kg over 20 minutes on days 1 and 15, and 19.
All Cause Mortality
	Paclitaxel, Bevacizumab & Pemetrexed
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Paclitaxel, Bevacizumab & Pemetrexed
	Affected / at Risk (%)	# Events
Total	20/44 (45.5%)
Blood and lymphatic system disorders
Febrile neutropenia	1/44 (2.3%)	1
Neutrophils/granulocytes (ANC/AGC)	1/44 (2.3%)	1
Gastrointestinal disorders
Diarrhea	1/44 (2.3%)	1
Esophagitis	1/44 (2.3%)	1
Nausea	1/44 (2.3%)	1
Perforation, GI- Small Bowel NOS	1/44 (2.3%)	1
Vomiting	1/44 (2.3%)	1
General disorders
Death not assoc w CTCAE term- Death NOS	1/44 (2.3%)	1
Edema: limb	1/44 (2.3%)	1
Fatigue (asthenia, lethargy, malaise)	2/44 (4.5%)	2
Infections and infestations
Inf norm ANC/gr1/2 neut-Pneumonia(lung)	2/44 (4.5%)	3
Infection, other	3/44 (6.8%)	3
Injury, poisoning and procedural complications
Fracture	1/44 (2.3%)	2
Wound complication, non-infectious	1/44 (2.3%)	1
Investigations
Hemoglobin	1/44 (2.3%)	1
Metabolism and nutrition disorders
Dehydration	1/44 (2.3%)	1
Musculoskeletal and connective tissue disorders
Pain - Back	2/44 (4.5%)	4
Pain - Chest wall	2/44 (4.5%)	2
Pain - Extremity-limb	2/44 (4.5%)	3
Nervous system disorders
Neuropathy: cranial - CN II Vision	1/44 (2.3%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)	3/44 (6.8%)	3
Hypoxia	2/44 (4.5%)	2
Pneumonitis/pulm infiltrates	1/44 (2.3%)	1
Pulm/upp respiratory - Other (spec)	1/44 (2.3%)	1
Vascular disorders
Hypotension	1/44 (2.3%)	1
Thrombosis/thrombus/embolism	1/44 (2.3%)	1
Vessel injury-artery- Other NOS	1/44 (2.3%)	1
Other (Not Including Serious) Adverse Events
	Paclitaxel, Bevacizumab & Pemetrexed
	Affected / at Risk (%)	# Events
Total	44/44 (100%)
Blood and lymphatic system disorders
Leukocytes (total WBC)	21/44 (47.7%)	87
Lymphopenia	19/44 (43.2%)	162
Gastrointestinal disorders
Mucositis (Clin exam)- Oral cavity	10/44 (22.7%)	26
Nausea	11/44 (25%)	35
General disorders
Fatigue (asthenia, lethargy, malaise)	30/44 (68.2%)	213
Pain - Pain NOS	28/44 (63.6%)	143
Investigations
ALT, SGPT	21/44 (47.7%)	116
AST, SGOT	11/44 (25%)	32
Creatinine	2/44 (4.5%)	2
Hemoglobin	18/44 (40.9%)	123
INR	2/44 (4.5%)	8
Neutrophils/granulocytes (ANC/AGC)	18/44 (40.9%)	45
PTT	2/44 (4.5%)	2
Metabolism and nutrition disorders
Albumin, low (hypoalbuminemia)	13/44 (29.5%)	37
Anorexia	21/44 (47.7%)	70
Glucose, high (hyperglycemia)	35/44 (79.5%)	176
Magnesium, low (hypomagnesemia)	2/44 (4.5%)	2
Phosphate, low (hypophosphatemia)	8/44 (18.2%)	13
Potassium, high (hyperkalemia)	6/44 (13.6%)	9
Potassium, low (hypokalemia)	4/44 (9.1%)	5
Sodium, low (hyponatremia)	2/44 (4.5%)	7
Musculoskeletal and connective tissue disorders
Pain - Muscle	21/44 (47.7%)	66
Nervous system disorders
Neuropathy: sensory	9/44 (20.5%)	21
Voice changes/dysarthria	8/44 (18.2%)	33
Respiratory, thoracic and mediastinal disorders
Cough	14/44 (31.8%)	35
Dyspnea (shortness of breath)	22/44 (50%)	84
Skin and subcutaneous tissue disorders
Hair loss/alopecia (scalp or body)	10/44 (22.7%)	49

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.