A Study of Biweekly Gemcitabine, Paclitaxel, and Avastin in Patients With Metastatic Breast Cancer

• Sponsor: Barbara Ann Karmanos Cancer Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT00618826
• Collaborator: Eli Lilly and Company (Industry), Genentech, Inc. (Industry)
• Enrollment: 14
• Location: 1
• Arm: 1
• Duration (Months): 87
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to look at a new chemotherapy schedule in metastatic breast cancer.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Breast Cancer	Drug: Paclitaxel; Drug: Gemcitabine; Drug: Avastin	Phase 2

Detailed Description

The purpose of this study is to determine whether a new chemotherapy schedule using biweekly combination of paclitaxel (Taxol®), gemcitabine (Gemzar®) and Avastin would help to lessen in-between-cycle growth of resistant cells and to evaluate the toxicity of this therapy.

Taxol is approved by the Food and Drug Administration (FDA) for use in metastatic breast and metastatic ovarian cancer but its use in this study is investigational. Gemzar is FDA approved for the use in breast, lung and pancreatic cancer but its use in this study is investigational.

The Avastin being given in this study is commercially available, however, it has not been approved by FDA for use in metastatic breast cancer.

Study Design

• Study Type: Interventional
• Actual Enrollment: 14 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of Biweekly Gemcitabine, Paclitaxel, and Avastin as Frontline Therapy for Metastatic Breast Cancer
• Study Start Date: Nov 1, 2006
• Actual Primary Completion Date: Feb 1, 2014
• Actual Study Completion Date: Feb 1, 2014

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment Period Treatment will be administered once every 2 weeks. One cycle of therapy will consist of 14 days. Paclitaxel is administered first after appropriate premedications. Gemcitabine is administered second and Avastin is administered after chemotherapy, all given on day 1 of each cycle.

Drug: Paclitaxel; Patients will be premedicated with dexamethasone and diphenhydramine hydrochloride. Patients will received 150mg of paclitaxel via IV over 120 mins.; Drug: Gemcitabine; Patients will receive 1500mg of Gemcitabine via IV over 30-60 minutes. Gemcitabine will be given after Paclitaxel.; Drug: Avastin; 10mg/kg will be given via IV over 90 mins (1st dose). Patients must remain under supervision for 1 hr after completion of the initial dose of Avastin. If no side effects occur, shortened, 60-min 2nd infusion, the post-infusion observation period for the subsequent infusions may be shortened to 20 minutes, and eliminated entirely with the fourth and subsequent infusions.

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival [maximum 50 months]

   Time from study entry to disease progression or death

Secondary Outcome Measures

1. Overall Response Rate [maximum 50 months]

   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.

Other Outcome Measures

1. Overall Survival (OS) at 3 Years [3 years]

   proportion of participants surviving 3 years

2. Toxicity [Duration of study]

   toxicities recorded using CTCAE definitions

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patient must be 18 years of age or older with histologically confirmed breast cancer and clinical evidence of metastatic disease.

• Patients must have measurable or non-measurable disease. X-rays, scans or physical examinations used to assess measurable disease must be performed within 28 days prior to registration. X-rays, scans or physical examinations to assess non-measurable disease must be completed within 42 days prior to registration. Patients with effusions or ascites as the only sites of disease are ineligible.

• Patients must meet the following requirements regarding prior and concurrent chemotherapy:Patients must not have received prior chemotherapy regimens for metastatic breast cancer. Patients may have received adjuvant/neoadjuvant chemotherapy, for a total of 3 prior regimens.

• Prior therapy with paclitaxel or docetaxel is allowed in the adjuvant or neoadjuvant setting, if given > 6 months prior to registration.

• Patients must have >14 days delay between the conclusion of any radiation and the start of gemcitabine, provided the acute effects of radiation treatment have resolved.

• Patients may have received any number of exogenous hormonal therapies and/or trastuzumab in the adjuvant, neoadjuvant or metastatic setting. Last dose of prior hormonal therapy at least 14 days prior to registration.

• Patients may receive concomitant bisphosphonate therapy for bone metastasis.

• Patients must have recovered from any prior surgery. Two weeks must have elapsed from the time of any minor surgery and 4 weeks of any major surgery.

• Patients must have adequate bone marrow reserve as evidenced by the following: ANC > 1500/mcL, platelets > 100, 000/mcL, and hemoglobin > 9.0 gm/dL. These results must be obtained within 28 days prior to registration.

• Patients must have serum creatinine < 1.5 mg/dL, obtained within 28 days prior to registration.

• Urine Protein: creatinine ratio ≥ 1.0 at screening.

• Patients must have adequate liver function.

• Patients must have a Zubrod performance status of 0-1.

Exclusion Criteria:

• Patients must not have tumors that carry HER-2 gene amplifications as determined by (i) fluorescence in situ hybridization (FISH) or (ii) overexpression of HER-2 protein 3+ level assessed by immunohistochemistry; or may have tumors that carry HER=2 gene amplification and have had disease progression while on trastuzumab. Patients who have previously been treated with trastuzumab must be off treatment at least 28 days prior to registration.

• Patients must not have CNS metastasis, leptomeningeal disease or lymphatic pulmonary metastases.

• Patients must not have had prior therapy with gemcitabine or bevacizumab.

• Patient must not have major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to start of treatment, anticipation of need for major surgical procedure during the course of the study.

• Patients must not have received radiation to > 50% of the marrow-bearing bone.

• Patients must not have a history of significant symptomatic cardiac disease or left ventricular ejection fraction (LVEF) < 50% of the institutional lower limit of normal (ILLN). An isotope cardiac scan (MUGA) and ECG must be obtained within 28 days.

• Patients with uncontrolled hypertension are NOT eligible (BP>150/100).

• Patients must not have pr-existing clinically significant (Grade 2 or greater per CTCAE Version 3.0 motor or sensory neuropathy except for abnormalities due to cancer.

• Patients known to be HIV positive.

• Patients must not be nursing or pregnant. Men and women of reproductive potential must agree to use an effective contraceptive method.

• No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or Stage II cancer from which the patient has been disease free for 5 years.

• Patients must not have had a Stroke or Myocardial Infarction in the past 6 months. Patients with unstable agina, significant peripheral vascular disease, history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within the last 6 months should be excluded.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201

Sponsors and Collaborators

• Barbara Ann Karmanos Cancer Institute
• Eli Lilly and Company
• Genentech, Inc.

Investigators

• Principal Investigator: Sayed Lavasani, M.D., Barbara Ann Karmanos Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sayeh Lavasani, Principal Investigator, Barbara Ann Karmanos Cancer Institute
• ClinicalTrials.gov Identifier: NCT00618826
• Other Study ID Numbers: 2007-050; 2007-050; B9E-US-I158; AVF3734s
• First Posted: Feb 20, 2008
• Last Update Posted: Apr 14, 2017
• Last Verified: Mar 1, 2017

• Keywords provided by Sayeh Lavasani, Principal Investigator, Barbara Ann Karmanos Cancer Institute: Breast cancer
• Additional relevant MeSH terms: Breast Neoplasms; Gemcitabine; Paclitaxel; Bevacizumab

Study Results

Participant Flow

Arm/Group Title	Paclitaxel + Gemcitabine + Avastin
Arm/Group Description	Treatment administered once every 2 weeks, 1 cycle will consist of 14 days. Paclitaxel (administered first) - Patients will be pre-medicated with dexamethasone and diphenhydramine hydrochloride. Patients will received 150mg of paclitaxel via IV over 120 mins. Gemcitabine (given after Paclitaxel) - Patients will receive 1500mg of Gemcitabine via IV over 30-60 minutes. Gemcitabine will be given after Paclitaxel. Avastin - 10mg/kg will be given via IV over 90 mins (1st dose). Patients must remain under supervision for 1 hr after completion of the initial dose of Avastin. If no side effects occur, shortened, 60-min 2nd infusion, the post-infusion observation period for the subsequent infusions may be shortened to 20 minutes, and eliminated entirely with the fourth and subsequent infusions.
Period Title: Overall Study
STARTED	14
COMPLETED	13
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Treatment Period
Arm/Group Description	Treatment will be administered once every 2 weeks. One cycle of therapy will consist of 14 days. Paclitaxel is administered first after appropriate premedications. Gemcitabine is administered second and Avastin is administered after chemotherapy, all given on day 1 of each cycle. Paclitaxel: Patients will be premedicated with dexamethasone and diphenhydramine hydrochloride. Patients will received 150mg of paclitaxel via IV over 120 mins. Gemcitabine: Patients will receive 1500mg of Gemcitabine via IV over 30-60 minutes. Gemcitabine will be given after Paclitaxel. Avastin: 10mg/kg will be given via IV over 90 mins (1st dose). Patients must remain under supervision for 1 hr after completion of the initial dose of Avastin. If no side effects occur, shortened, 60-min 2nd infusion, the post-infusion observation period for the subsequent infusions may be shortened to 20 minutes, and eliminated entirely with the fourth and subsequent infusions.
Overall Participants	14
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	53.5
Sex: Female, Male (Count of Participants)
Female	14 100%
Male	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	14 100%
Unknown or Not Reported	0 0%
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	4 28.6%
White	10 71.4%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	14 100%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival
Description	Time from study entry to disease progression or death
Time Frame	maximum 50 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment
Arm/Group Description	Paclitaxel / Gemcitabine
Measure Participants	13
Median (95% Confidence Interval) [months]	43

2. Secondary Outcome

Title	Overall Response Rate
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	maximum 50 months

Outcome Measure Data

Analysis Population Description

patients with measurable disease

Arm/Group Title	Arm 1
Arm/Group Description	all participants
Measure Participants	13
Number (95% Confidence Interval) [proportion of participants]	0.46 3.3%

3. Other Pre-specified Outcome

Title	Overall Survival (OS) at 3 Years
Description	proportion of participants surviving 3 years
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Other Pre-specified Outcome

Title	Toxicity
Description	toxicities recorded using CTCAE definitions
Time Frame	Duration of study

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	Treatment Period
Arm/Group Description	Treatment will be administered once every 2 weeks. One cycle of therapy will consist of 14 days. Paclitaxel is administered first after appropriate premedications. Gemcitabine is administered second and Avastin is administered after chemotherapy, all given on day 1 of each cycle.
All Cause Mortality
	Treatment Period
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment Period
	Affected / at Risk (%)	# Events
Total	10/14 (71.4%)
Blood and lymphatic system disorders
Hemoglobin	2/14 (14.3%)	2
Lymphopenia	1/14 (7.1%)	1
Cardiac disorders
Cardiac ischemia/infarction	1/14 (7.1%)	1
Hypertension	2/14 (14.3%)	2
Hypotension	1/14 (7.1%)	1
Gastrointestinal disorders
Constipation	1/14 (7.1%)	1
Diarrhea	1/14 (7.1%)	1
Heartburn/dyspepsia	1/14 (7.1%)	1
General disorders
Fatigue (asthenia, lethargy, malaise)	2/14 (14.3%)	2
Rigors/chills	1/14 (7.1%)	1
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils-Skin (cellulitis)	1/14 (7.1%)	1
Infection with unknown ANC - Bronchus	1/14 (7.1%)	1
Infection with unknown ANC - Lung (pneumonia)	1/14 (7.1%)	3
Infection with unknown ANC - Upper airway NOS	1/14 (7.1%)	1
Investigations
AST, SGOT (serum glutamic oxaloacetic transaminase)	1/14 (7.1%)	1
GGT (gamma-Glutamyl transpeptidase)	1/14 (7.1%)	1
Glucose, serum-high (hyperglycemia)	3/14 (21.4%)	3
Potassium, serum-high (hyperkalemia)	1/14 (7.1%)	2
Musculoskeletal and connective tissue disorders
Pain-Extremity-limb	3/14 (21.4%)	3
Pain-Joint	1/14 (7.1%)	1
Pain-Muscle	1/14 (7.1%)	1
Pain-Pain NOS	1/14 (7.1%)	1
Pain-Other (Specify,_)	1/14 (7.1%)	1
Nervous system disorders
Syncope (fainting)	1/14 (7.1%)	1
Neuropathy: sensory	2/14 (14.3%)	2
Psychiatric disorders
Confusion	1/14 (7.1%)	2
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)	3/14 (21.4%)	4
Pleural effusion (non-malignant)	1/14 (7.1%)	1
Skin and subcutaneous tissue disorders
Dermatology/Skin-Other (Specify,_)	1/14 (7.1%)	2
Rash/desquamation	1/14 (7.1%)	1
Ulceration	1/14 (7.1%)	1
Other (Not Including Serious) Adverse Events
	Treatment Period
	Affected / at Risk (%)	# Events
Total	14/14 (100%)
Blood and lymphatic system disorders
Blood/Bone Marrow - Other (Specify,_)	1/14 (7.1%)	1
Hemoglobin	11/14 (78.6%)	16
Leukocytes (total WBC)	3/14 (21.4%)	3
Lymphopenia	3/14 (21.4%)	6
Neutrophils/granulocytes (ANC/AGC)	1/14 (7.1%)	2
Platelets	10/14 (71.4%)	13
Thrombotic microangiopathy (e.g., thrombocytopenic purpura [TTP] or hemolytic uremic syndrome [HUS])	1/14 (7.1%)	1
Cardiac disorders
Supraventricular and nodal arrhythmia-Sinus tachycardia	1/14 (7.1%)	1
Supraventricular and nodal arrhythmia-Supraventricular tachycardia	1/14 (7.1%)	1
Hypertension	5/14 (35.7%)	5
Ear and labyrinth disorders
Pain-External ear	1/14 (7.1%)	1
Endocrine disorders
Hot flashes/flushes	1/14 (7.1%)	1
Eye disorders
Dry eye syndrome	1/14 (7.1%)	1
Ophthalmoplegia/diplopia (double vision)	1/14 (7.1%)	1
Vision-blurred vision	4/14 (28.6%)	4
Vision-flashing lights/floaters	1/14 (7.1%)	1
Gastrointestinal disorders
Anorexia	5/14 (35.7%)	7
Constipation	2/14 (14.3%)	2
Diarrhea	6/14 (42.9%)	7
Dry mouth/salivary gland (xerostomia)	1/14 (7.1%)	1
Gastrointestinal- Other (Specify,_)	1/14 (7.1%)	1
Mucositis/stomatitis (clinical exam)-Oral cavity	4/14 (28.6%)	5
Nausea	10/14 (71.4%)	15
Vomiting	8/14 (57.1%)	12
Hemorrhage/Bleeding - Other (Specify,_)	1/14 (7.1%)	1
Hemorrhage, GI-Varices (rectal)	1/14 (7.1%)	1
General disorders
Constitutional Symptoms-Other(Specify,_)	1/14 (7.1%)	1
Fatigue (asthenia, lethargy, malaise)	12/14 (85.7%)	26
Fever (in the absense of neutropenia is defined as ANC <1.0 x10e9/L)	4/14 (28.6%)	5
Edema: limb-1	3/14 (21.4%)	3
Rigors/chills	4/14 (28.6%)	4
Sweating (diaphoresis)	2/14 (14.3%)	3
Edema: head and neck	1/14 (7.1%)	1
Edema:limb	3/14 (21.4%)	3
Pain-Face	1/14 (7.1%)	1
Pain-Head/headache	3/14 (21.4%)	3
Pain	1/14 (7.1%)	1
Pain-Pain NOS	6/14 (42.9%)	7
Pain-Other (Specify,_)	1/14 (7.1%)	2
Immune system disorders
Allergic reaction/hypersensitivity (including drug fever)	1/14 (7.1%)	1
Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)	4/14 (28.6%)	5
Infections and infestations
Febrile neutropenia (fever of unknown origin without clinically or microbiologically documented infe	1/14 (7.1%)	1
Infection with normal ANC or Grade 1 or 2 neutrophils-Bronchus	1/14 (7.1%)	1
Infection with normal ANC or Grade 1 or 2 neutrophils-Oral cavity-gums (gingivitis)	1/14 (7.1%)	1
Infection with normal ANC or Grade 1 or 2 neutrophils - Skin (cellulitis)	1/14 (7.1%)	1
Infection with unknown ANC-Bronchus	1/14 (7.1%)	1
Infection with unknown ANC-Nose	1/14 (7.1%)	1
Infection with unknown ANC-Paranasal	1/14 (7.1%)	1
Infection with unknown ANC-Pharynx	2/14 (14.3%)	2
Infection with unknown ANC-Skin (cellulitis)	2/14 (14.3%)	3
Infection with unknown ANC-Upper airway NOS	1/14 (7.1%)	1
Infection with unknown ANC-Urinary tract NOS	1/14 (7.1%)	1
Infection with unknown ANC-Wound	1/14 (7.1%)	1
Infection	1/14 (7.1%)	1
Investigations
Weight loss	5/14 (35.7%)	5
Albumin, serum-low (hypoalbuminemia)	1/14 (7.1%)	1
Alkaline phosphatase	5/14 (35.7%)	6
ALT,SGPT (serum glutamic pyruvic transaminase)	5/14 (35.7%)	7
AST,SGOT (serum glutamic oxaloacetic transaminase)	6/14 (42.9%)	6
Bilirubin(hyperbilirubinemia)	1/14 (7.1%)	1
Calcium, serum-high (hypercalcemia)	1/14 (7.1%)	1
Calcium, serum-low (hypocalcemia)	1/14 (7.1%)	1
Creatinine	2/14 (14.3%)	3
Glucose, serum-high (hyperglycemia)	12/14 (85.7%)	23
Glucose, serum-low (hypoglycemia)	1/14 (7.1%)	1
Magnesium, serum-low (hypomagnesemia)	1/14 (7.1%)	1
Metabolic/Laboratory - Other (Specify,_)	2/14 (14.3%)	2
Potassium, serum-high (hyperkalemia)	1/14 (7.1%)	1
Potassium, serum-low (hypokalemia)	1/14 (7.1%)	1
Proteinuria	7/14 (50%)	16
Sodium, serum-low (hyponatremia)	2/14 (14.3%)	2
Uric acid, serum-high (hyperuricemia)	2/14 (14.3%)	2
Musculoskeletal and connective tissue disorders
Pain-Back	4/14 (28.6%)	7
Pain-Bone	3/14 (21.4%)	4
Pain-Chest wall	1/14 (7.1%)	1
Pain-Extremity-limb	5/14 (35.7%)	6
Pain-Joint	4/14 (28.6%)	4
Pain-Muscle	3/14 (21.4%)	3
Nervous system disorders
Dizziness	1/14 (7.1%)	1
Mood alteration-Anxiety	3/14 (21.4%)	3
Mood alteration-Depression	2/14 (14.3%)	2
Neurology- Other(Specify,_)	1/14 (7.1%)	1
Neuropathy: motor	1/14 (7.1%)	1
Neuropathy: sensory	10/14 (71.4%)	19
Renal and urinary disorders
Incontinence, urinary	1/14 (7.1%)	1
Renal/Genitourinary-Other(Specify,_)	2/14 (14.3%)	3
Urinary retention (including neurogenic bladder)	1/14 (7.1%)	1
Reproductive system and breast disorders
Vaginal mucositis	1/14 (7.1%)	1
Respiratory, thoracic and mediastinal disorders
Hemorrhage,pulmonary/upper respiratory-Nose	7/14 (50%)	8
Pain-Throat/pharynx/larynx	3/14 (21.4%)	3
Bronchospasm,wheezing	1/14 (7.1%)	1
Cough	6/14 (42.9%)	7
Dyspnea (shortness of breath)	4/14 (28.6%)	7
Nasal cavity/paranasal sinus reaction	5/14 (35.7%)	5
Pleural effusion (non-malignant)	1/14 (7.1%)	1
Pulmonary/Upper Respiratory-Other (Specify,_)	2/14 (14.3%)	2
Voice changes/dysarthria (e.g. hoarseness, loss or alteration in voice, laryngitis)	1/14 (7.1%)	1
Skin and subcutaneous tissue disorders
Bruising (in absence of Grade 3 or 4 thrombocytopenia)	1/14 (7.1%)	2
Dermatology/Skin-Other (Specify,_)	3/14 (21.4%)	6
Dry skin	2/14 (14.3%)	2
Hair loss/alopecia (scalp or body)	6/14 (42.9%)	6
Nail changes	3/14 (21.4%)	3
Pruritus/itching	1/14 (7.1%)	2
Rash/desquamation	2/14 (14.3%)	2
Rash: acne/acneiform	1/14 (7.1%)	1
Rash:erythema multiforme (e.g., Steven-Johnson syndrome, toxic epidermal necrolysis)	2/14 (14.3%)	2
Rash: hand-foot skin reaction	2/14 (14.3%)	4
Skin breakdown/decubitus ulcer	1/14 (7.1%)	1
Ulceration	1/14 (7.1%)	1
Vascular disorders
Hematoma	1/14 (7.1%)	1
Lymphedema-related fibrosis	1/14 (7.1%)	1

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.