Avastin +/- Erlotinib Consolidation Chemotherapy After Carboplatin, Paclitaxel, and Avastin (CTA) Induction Therapy for Advanced Ovarian, Fallopian Tube, Primary Peritoneal Cancer & Papillary Serous or Clear Cell Mullerian Tumors

• Sponsor: Dana-Farber Cancer Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT00520013
• Collaborator: Genentech, Inc. (Industry), Beth Israel Deaconess Medical Center (Other), Brigham and Women's Hospital (Other), Massachusetts General Hospital (Other)
• Enrollment: 60
• Locations: 3
• Arms: 3
• Duration (Months): 75
• Patients Per Site: 20
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this research study is to evaluate how patients with newly diagnosed advanced ovarian, fallopian tube, primary peritoneal cancer and papillary serous or clear cell mullerian tumors respond to consolidation therapy with Avastin and erlotinib or Avastin alone over 1 year. These drugs have been used in the treatment of other types of cancers and information from those studies suggests that these agents may help to treat the cancers studied here.

Condition or Disease	Intervention/Treatment	Phase
Ovarian Cancer; Fallopian Tube Cancer; Primary Peritoneal Cancer; Papillary Serous Mullerian Tumor; Clear Cell Mullerian Tumor	Drug: bevacizumab; Drug: erlotinib; Drug: paclitaxel; Drug: carboplatin	Phase 2

Detailed Description

Objectives:

Primary To examine the progression free survival (PFS) of Avastin and Erlotinib (AE) or Avastin (A) as consolidation therapy.

Secondary To examine the toxicity between the two consolidative regimens AE vs. A. To assess the response rate of CTA.

STATISTICAL DESIGN This study uses a randomized selection design. Both consolidation treatment arms are deemed experimental and are compared against a historical control [McGuire WP et al. Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer. NEJM 1996: 334:1-6. PMID:7494563]. With 30 patients in a given arm and 6 months of follow-up, there was 80% power to detect a 61.5% increase in median PFS from 13 months to 21 months assuming 1-sided 10% significance.

Study Design

• Study Type: Interventional
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Phase II Trial of Avastin (A) or Avastin and Erlotinib (AE) as First Line Consolidation Chemotherapy After Carboplatin, Paclitaxel, and Avastin (CTA) Induction Therapy for Newly Diagnosed Advanced Ovarian, Fallopian Tube, Primary Peritoneal Cancer & Papillary Serous or Clear Cell Mullerian Tumors
• Study Start Date: Aug 1, 2007
• Actual Primary Completion Date: Oct 1, 2010
• Actual Study Completion Date: Nov 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: carboplatin/paclitaxel/bevacizumab then bevacizumab Induction (CTA): Patients received carboplatin IV AUC 5, paclitaxel IV 175 mg/m2 and bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle for 6 cycles. Bevacizumab started with cycle 2. Patients with disease progression based on radiographic evaluation after induction could not advance to the randomized consolidation phase. Consolidation (A): Patients received bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle for 1 year.	Drug: bevacizumab; Other Names: Avastin rhuMAB VEGF ; Drug: paclitaxel; Other Names: Taxol ; Drug: carboplatin; Other Names: Paraplatin
Experimental: carboplatin/paclitaxel/bevacizumab then bevacizumab/erlotinib Induction (CTA): Patients received carboplatin IV AUC 5, paclitaxel IV 175 mg/m2 and bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle for 6 cycles. Bevacizumab started with cycle 2. Patients with disease progression based on radiographic evaluation after induction could not advance to the randomized consolidation phase. Consolidation (AE): Patients received bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle and oral erlotinib 150mg daily for 1 year.	Drug: bevacizumab; Other Names: Avastin rhuMAB VEGF ; Drug: erlotinib; Other Names: Tarceeva ; Drug: paclitaxel; Other Names: Taxol ; Drug: carboplatin; Other Names: Paraplatin
Experimental: carboplatin/paclitaxel/bevacizumab Induction (CTA): Patients received carboplatin IV AUC 5, paclitaxel IV 175 mg/m2 and bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle for 6 cycles. Bevacizumab started with cycle 2. Patients with disease progression based on radiographic evaluation after induction could not advance to the randomized consolidation phase. Consolidation: None	Drug: bevacizumab; Other Names: Avastin rhuMAB VEGF ; Drug: paclitaxel; Other Names: Taxol ; Drug: carboplatin; Other Names: Paraplatin

Outcome Measures

Primary Outcome Measures

1. Consolidation Progression-Free Survival [Assessments occurred every cycle (serologic) and every 3 cycles (radiologic) on consolidation treatment. Pts were allowed on consolidation therapy for up to 1 year and upon treatment discontinuation were followed for another year.]

   Consolidation PFS based on the Kaplan-Meier method was defined as the time from the first day of consolidation therapy to documented disease progression (PD) or disease-specific death. Based on RECIST 1.1, radiographic PD was defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum since beginning consolidation, the appearence of one or more new lesions and/or unequivocal progression of existing non-target lesions. Based on Rustin criteria, serlogic PD was a rise in CA125 since beginning of consolidation or previously normal CA125 that rises to >/= 2xULN with either event documented on 2 occasions. Patients who were event-free were censored at the date of their last disease evaluation.

2. Consolidation Treatment-related Toxicity Rate [Assessed every cycle during consolidation treatment and up to 30 days post-treatment. Per protocol, consolidation treatment was a fixed duration of 1 year.]

   Consolidation treatment-related toxicity rates based on CTCAEv3 were defined as rates of maximum grade 3 or higher toxicity events with attribution possible, probable or definite occurring during consolidation treatment and up to 30 days post-treatment.

Secondary Outcome Measures

1. Consolidation Objective Response Rate [Assessments occurred every cycle (serologic) and every 3 cycles (radiologic) on consolidation treatment. Pts were allowed on consolidation therapy for up to 1 year.]

   Consolidation objective response (OR) was based on RECIST 1.0 criteria with OR defined as achieving partial response (PR) or complete response (CR). Per RECIST 1.0 for target lesions, CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. For CR or PR, changes in tumor measurements must be confirmed by repeat assessments performed no fewer than 4 weeks after the response criteria are first met. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions. If CA125 disease then OR based on Rustin criteria is a 50% decrease in serum CA125 level from two initially elevated samples confirmed by a 4th sample.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• 18 years of age and older

• Histological diagnosis of epithelial ovarian carcinoma, fallopian tube cancer, primary peritoneal carcinoma, or papillary serous mullerian carcinoma

• Previous attempted surgical debulking

• Stage III or IV

• Willing and able to undergo second look laparoscopy

• Performance status 0-1 by ECOG scale

• Peripheral neuropathy < grade 2

• Life expectancy of 6 months or greater

Exclusion Criteria:

• Patients with clinically significant cardiovascular disease as outlined in the protocol

• Neutrophil count < 1,500/mm3; platelet count <100,000/m3

• Alkaline phosphatase or bilirubin > 1.5 x ULN, SGOT > 5 x ULN

• Calculated creatinine clearance < 50ml/min

• Prior chemotherapy or radiotherapy for other malignancy except for the treatment for localized breast cancer greater than five years prior to diagnosis

• No more than one cycle of first line chemotherapy with carboplatin and paclitaxel

• Inadequate surgical cytoreduction such that interval cytoreductive surgery could materially improve prognosis

• Concurrent invasive malignancy

• Evidence of bleeding diathesis or coagulopathy

• Evidence of tumor involving major blood vessels on any prior CT scans

• Surgical wound that has failed to close

• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, or anticipation of need for major surgical procedure during the course of this study

• Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment

• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to day 0

• Serious non-healing wound, ulcer, or bone fracture

• Prior treatment with an anti-angiogenic agent

• Any active bleeding

• Active psychiatric disease or neurologic symptoms requiring treatment

• Presence of central nervous system brain metastases

• Proteinuria at screening as demonstrated by criteria in protocol

• Dementia or significantly altered mental status that would prohibit the understanding and/or giving of informed consent

• Known hypersensitivity to Cremophor EL or any component of Avastin

• Active bacterial, viral, or fungal infections

• Receiving any other investigational agent

• History of gastrointestinal perforation

• Prior therapies targeting the epidermal growth factor receptor

• Symptoms of bowel obstruction

• Dependence on TPN or IV hydration

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
2	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02115
3	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115

Sponsors and Collaborators

• Dana-Farber Cancer Institute
• Genentech, Inc.
• Beth Israel Deaconess Medical Center
• Brigham and Women's Hospital
• Massachusetts General Hospital

Investigators

• Principal Investigator: Susana Campos, MD, MPH, Dana-Farber Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Susana M. Campos, MD, Medical Oncologist., Dana-Farber Cancer Institute
• ClinicalTrials.gov Identifier: NCT00520013
• Other Study ID Numbers: 07-039
• First Posted: Aug 23, 2007
• Last Update Posted: Jul 27, 2018
• Last Verified: Jul 1, 2018

• Additional relevant MeSH terms: Neoplasms; Fallopian Tube Neoplasms; Peritoneal Neoplasms; Mixed Tumor, Mullerian; Paclitaxel; Bevacizumab; Carboplatin; Erlotinib Hydrochloride

Study Results

Participant Flow

Recruitment Details	Sixty patients were enrolled between Aug 3, 2007 and Jan 6, 2010.
Pre-assignment Detail	Patients with disease progression based on radiographic evaluation after induction could not advance to the randomized consolidation phase.

Arm/Group Title	Carboplatin/Paclitaxel/Bevacizumab Then Bevacizumab	Carboplatin/Paclitaxel/Bevacizumab Then Bevacizumab/Erlotinib	Carboplatin/Paclitaxel/Bevacizumab
Arm/Group Description	Induction (CTA): Patients received carboplatin IV AUC 5, paclitaxel IV 175 mg/m2 and bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle for 6 cycles. Bevacizumab started with cycle 2. Patients with disease progression based on radiographic evaluation after induction could not advance to the randomized consolidation phase. Consolidation (A): Patients received bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle for 1 year.	Induction (CTA): Patients received carboplatin IV AUC 5, paclitaxel IV 175 mg/m2 and bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle for 6 cycles. Bevacizumab started with cycle 2. Patients with disease progression based on radiographic evaluation after induction could not advance to the randomized consolidation phase. Consolidation (AE): Patients received bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle and oral erlotinib 150mg daily for 1 year.	Induction (CTA): Patients received carboplatin IV AUC 5, paclitaxel IV 175 mg/m2 and bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle for 6 cycles. Bevacizumab started with cycle 2. Patients with disease progression based on radiographic evaluation after induction could not advance to the randomized consolidation phase. Consolidation: None
Period Title: Overall Study
STARTED	23	25	11
Treated	23	25	11
COMPLETED	11	10	0
NOT COMPLETED	12	15	11

Baseline Characteristics

Arm/Group Title	Carboplatin/Paclitaxel/Bevacizumab Then Bevacizumab	Carboplatin/Paclitaxel/Bevacizumab Then Bevacizumab/Erlotinib	Carboplatin/Paclitaxel/Bevacizumab	Total
Arm/Group Description	Induction (CTA): Patients received carboplatin IV AUC 5, paclitaxel IV 175 mg/m2 and bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle for 6 cycles. Bevacizumab started with cycle 2. Patients with disease progression based on radiographic evaluation after induction could not advance to the randomized consolidation phase. Consolidation (A): Patients received bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle for 1 year. bevacizumab paclitaxel carboplatin	Induction (CTA): Patients received carboplatin IV AUC 5, paclitaxel IV 175 mg/m2 and bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle for 6 cycles. Bevacizumab started with cycle 2. Patients with disease progression based on radiographic evaluation after induction could not advance to the randomized consolidation phase. Consolidation (AE): Patients received bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle and oral erlotinib 150mg daily for 1 year. bevacizumab erlotinib paclitaxel carboplatin	Induction (CTA): Patients received carboplatin IV AUC 5, paclitaxel IV 175 mg/m2 and bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle for 6 cycles. Bevacizumab started with cycle 2. Patients with disease progression based on radiographic evaluation after induction could not advance to the randomized consolidation phase. Consolidation: None bevacizumab paclitaxel carboplatin	Total of all reporting groups
Overall Participants	23	25	11	59
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	58	56	54	57
Sex: Female, Male (Count of Participants)
Female	23 100%	25 100%	11 100%	59 100%
Male	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	23 100%	25 100%	11 100%	59 100%
Cancer Type (participants) [Number]
Primary peritoneal	4 17.4%	1 4%	1 9.1%	6 10.2%
Fallopian tube	5 21.7%	4 16%	1 9.1%	10 16.9%
Epithelial ovarian	10 43.5%	17 68%	8 72.7%	35 59.3%
Uterine papillary serous	2 8.7%	1 4%	1 9.1%	4 6.8%
Other (mixed, carcinosarcoma)	2 8.7%	2 8%	0 0%	4 6.8%

Outcome Measures

1. Primary Outcome

Title	Consolidation Progression-Free Survival
Description	Consolidation PFS based on the Kaplan-Meier method was defined as the time from the first day of consolidation therapy to documented disease progression (PD) or disease-specific death. Based on RECIST 1.1, radiographic PD was defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum since beginning consolidation, the appearence of one or more new lesions and/or unequivocal progression of existing non-target lesions. Based on Rustin criteria, serlogic PD was a rise in CA125 since beginning of consolidation or previously normal CA125 that rises to >/= 2xULN with either event documented on 2 occasions. Patients who were event-free were censored at the date of their last disease evaluation.
Time Frame	Assessments occurred every cycle (serologic) and every 3 cycles (radiologic) on consolidation treatment. Pts were allowed on consolidation therapy for up to 1 year and upon treatment discontinuation were followed for another year.

Outcome Measure Data

Analysis Population Description

The analysis dataset is comprised of patients randomized to consolidation treatment.

Arm/Group Title	Carboplatin/Paclitaxel/Bevacizumab Then Bevacizumab	Carboplatin/Paclitaxel/Bevacizumab Then Bevacizumab/Erlotinib
Arm/Group Description	Induction (CTA): Patients received carboplatin IV AUC 5, paclitaxel IV 175 mg/m2 and bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle for 6 cycles. Bevacizumab started with cycle 2. Patients with disease progression based on radiographic evaluation after induction could not advance to the randomized consolidation phase. Consolidation (A): Patients received bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle for 1 year.	Induction (CTA): Patients received carboplatin IV AUC 5, paclitaxel IV 175 mg/m2 and bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle for 6 cycles. Bevacizumab started with cycle 2. Patients with disease progression based on radiographic evaluation after induction could not advance to the randomized consolidation phase. Consolidation (AE): Patients received bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle and oral erlotinib 150mg daily for 1 year.
Measure Participants	23	25
Median (95% Confidence Interval) [months]	13.3	18.9

2. Primary Outcome

Title	Consolidation Treatment-related Toxicity Rate
Description	Consolidation treatment-related toxicity rates based on CTCAEv3 were defined as rates of maximum grade 3 or higher toxicity events with attribution possible, probable or definite occurring during consolidation treatment and up to 30 days post-treatment.
Time Frame	Assessed every cycle during consolidation treatment and up to 30 days post-treatment. Per protocol, consolidation treatment was a fixed duration of 1 year.

Outcome Measure Data

Analysis Population Description

The analysis dataset is comprised of patients who were randomized to consolidation treatment.

Arm/Group Title	Carboplatin/Paclitaxel/Bevacizumab Then Bevacizumab	Carboplatin/Paclitaxel/Bevacizumab Then Bevacizumab/Erlotinib
Arm/Group Description	Induction (CTA): Patients received carboplatin IV AUC 5, paclitaxel IV 175 mg/m2 and bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle for 6 cycles. Bevacizumab started with cycle 2. Patients with disease progression based on radiographic evaluation after induction could not advance to the randomized consolidation phase. Consolidation (A): Patients received bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle for 1 year.	Induction (CTA): Patients received carboplatin IV AUC 5, paclitaxel IV 175 mg/m2 and bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle for 6 cycles. Bevacizumab started with cycle 2. Patients with disease progression based on radiographic evaluation after induction could not advance to the randomized consolidation phase. Consolidation (AE): Patients received bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle and oral erlotinib 150mg daily for 1 year.
Measure Participants	23	25
Number (95% Confidence Interval) [percentage of participants]	30.4 132.2%	72.0 288%

3. Secondary Outcome

Title	Consolidation Objective Response Rate
Description	Consolidation objective response (OR) was based on RECIST 1.0 criteria with OR defined as achieving partial response (PR) or complete response (CR). Per RECIST 1.0 for target lesions, CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. For CR or PR, changes in tumor measurements must be confirmed by repeat assessments performed no fewer than 4 weeks after the response criteria are first met. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions. If CA125 disease then OR based on Rustin criteria is a 50% decrease in serum CA125 level from two initially elevated samples confirmed by a 4th sample.
Time Frame	Assessments occurred every cycle (serologic) and every 3 cycles (radiologic) on consolidation treatment. Pts were allowed on consolidation therapy for up to 1 year.

Outcome Measure Data

Analysis Population Description

The analysis dataset is comprised of all patient who started consolidation treatment.

Arm/Group Title	Carboplatin/Paclitaxel/Bevacizumab Then Bevacizumab	Carboplatin/Paclitaxel/Bevacizumab Then Bevacizumab/Erlotinib
Arm/Group Description	Induction (CTA): Patients received carboplatin IV AUC 5, paclitaxel IV 175 mg/m2 and bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle for 6 cycles. Bevacizumab started with cycle 2. Patients with disease progression based on radiographic evaluation after induction could not advance to the randomized consolidation phase. Consolidation (A): Patients received bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle for 1 year.	Induction (CTA): Patients received carboplatin IV AUC 5, paclitaxel IV 175 mg/m2 and bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle for 6 cycles. Bevacizumab started with cycle 2. Patients with disease progression based on radiographic evaluation after induction could not advance to the randomized consolidation phase. Consolidation (AE): Patients received bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle and oral erlotinib 150mg daily for 1 year.
Measure Participants	23	25
Number (95% Confidence Interval) [proportion of patients]	0.65	.60

Adverse Events

Time Frame	Assessed each cycle throughout consolidation treatment from time of first dose and up to day 30 post-treatment. Per protocol, consolidation treatment was a fixed duration of 1 year.
Adverse Event Reporting Description	Serious and other AE data is only available for consolidation treatment reflecting the primary and secondary study objectives centered on the evaluation of consolidative regimens AE vs A.
Arm/Group Title	Carboplatin/Paclitaxel/Bevacizumab Then Bevacizumab		Carboplatin/Paclitaxel/Bevacizumab Then Bevacizumab/Erlotinib
Arm/Group Description	Induction (CTA): Patients received carboplatin IV AUC 5, paclitaxel IV 175 mg/m2 and bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle for 6 cycles. Bevacizumab started with cycle 2. Patients with disease progression based on radiographic evaluation after induction could not advance to the randomized consolidation phase. Consolidation (A): Patients received bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle for 1 year.		Induction (CTA): Patients received carboplatin IV AUC 5, paclitaxel IV 175 mg/m2 and bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle for 6 cycles. Bevacizumab started with cycle 2. Patients with disease progression based on radiographic evaluation after induction could not advance to the randomized consolidation phase. Consolidation (AE): Patients received bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle and oral erlotinib 150mg daily for 1 year.
All Cause Mortality
	Carboplatin/Paclitaxel/Bevacizumab Then Bevacizumab		Carboplatin/Paclitaxel/Bevacizumab Then Bevacizumab/Erlotinib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Carboplatin/Paclitaxel/Bevacizumab Then Bevacizumab		Carboplatin/Paclitaxel/Bevacizumab Then Bevacizumab/Erlotinib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/23 (30.4%)		18/25 (72%)
Blood and lymphatic system disorders
Hemoglobin	0/23 (0%)		1/25 (4%)
Gastrointestinal disorders
Colitis	0/23 (0%)		1/25 (4%)
Diarrhea w/o prior colostomy	0/23 (0%)		5/25 (20%)
Enteritis	0/23 (0%)		1/25 (4%)
General disorders
Fatigue	1/23 (4.3%)		1/25 (4%)
Infections and infestations
Infection-other	0/23 (0%)		1/25 (4%)
Injury, poisoning and procedural complications
Wound - non-infectious	0/23 (0%)		1/25 (4%)
Metabolism and nutrition disorders
Hyponatremia	0/23 (0%)		1/25 (4%)
Musculoskeletal and connective tissue disorders
Extremity-limb, pain	0/23 (0%)		1/25 (4%)
Joint, pain	1/23 (4.3%)		0/25 (0%)
Muscle, pain	1/23 (4.3%)		0/25 (0%)
Reproductive system and breast disorders
Irregular menses	0/23 (0%)		1/25 (4%)
Skin and subcutaneous tissue disorders
Nail changes	0/23 (0%)		1/25 (4%)
Rash/desquamation	0/23 (0%)		1/25 (4%)
Rash: acne/acneiform	0/23 (0%)		3/25 (12%)
Vascular disorders
Hypertension	6/23 (26.1%)		4/25 (16%)
Hemorrhage-other	0/23 (0%)		1/25 (4%)
Other (Not Including Serious) Adverse Events
	Carboplatin/Paclitaxel/Bevacizumab Then Bevacizumab		Carboplatin/Paclitaxel/Bevacizumab Then Bevacizumab/Erlotinib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/23 (100%)		25/25 (100%)
Blood and lymphatic system disorders
Hemoglobin	8/23 (34.8%)		8/25 (32%)
Lymphatics-other	0/23 (0%)		1/25 (4%)
Cardiac disorders
C-P arrest, non-fatal, cause unk	1/23 (4.3%)		0/25 (0%)
Ear and labyrinth disorders
Tinnitus	1/23 (4.3%)		0/25 (0%)
Eye disorders
Vision-blurred	2/23 (8.7%)		0/25 (0%)
Gastrointestinal disorders
Abdomen, pain	3/23 (13%)		1/25 (4%)
Constipation	5/23 (21.7%)		6/25 (24%)
Dental/teeth/peridontal	1/23 (4.3%)		0/25 (0%)
Diarrhea w/o prior colostomy	5/23 (21.7%)		18/25 (72%)
Dry mouth	1/23 (4.3%)		0/25 (0%)
Dyspepsia	3/23 (13%)		0/25 (0%)
Esophagitis	0/23 (0%)		1/25 (4%)
GI-other	0/23 (0%)		3/25 (12%)
Hemorrhoids	0/23 (0%)		3/25 (12%)
Intestine, pain	1/23 (4.3%)		0/25 (0%)
Lip, pain	0/23 (0%)		1/25 (4%)
Muco/stomatitis (symptom) oral cavity	1/23 (4.3%)		4/25 (16%)
Muco/stomatitis (symptom) stomach	0/23 (0%)		1/25 (4%)
Muco/stomatitis by exam, oral cavity	0/23 (0%)		2/25 (8%)
Nausea	5/23 (21.7%)		9/25 (36%)
Oral cavity, hemorrhage	3/23 (13%)		1/25 (4%)
Oral cavity, pain	0/23 (0%)		3/25 (12%)
Oral gums, pain	1/23 (4.3%)		0/25 (0%)
Rectum, hemorrhage	1/23 (4.3%)		0/25 (0%)
Salivary	0/23 (0%)		1/25 (4%)
Vomiting	2/23 (8.7%)		1/25 (4%)
General disorders
Chest/thoracic pain NOS	0/23 (0%)		1/25 (4%)
Constitutional, other	0/23 (0%)		1/25 (4%)
Edema limb	1/23 (4.3%)		3/25 (12%)
Face, pain	1/23 (4.3%)		0/25 (0%)
Fatigue	18/23 (78.3%)		21/25 (84%)
Fever w/o neutropenia	0/23 (0%)		2/25 (8%)
Pain-other	2/23 (8.7%)		1/25 (4%)
Rigors/chills	0/23 (0%)		2/25 (8%)
Infections and infestations
Infection Gr0-2 neut, lip/perioral	0/23 (0%)		1/25 (4%)
Infection Gr0-2 neut, meninges	0/23 (0%)		1/25 (4%)
Infection Gr0-2 neut, skin	0/23 (0%)		1/25 (4%)
Infection Gr0-2 neut, urinary tract	1/23 (4.3%)		1/25 (4%)
Infection Gr0-2 neut, wound	0/23 (0%)		1/25 (4%)
Infection w/ gr3-4 neut, anal/perianal	0/23 (0%)		1/25 (4%)
Infection w/ gr3-4 neut, skin	0/23 (0%)		1/25 (4%)
Infection w/ unk ANC ungual (nails)	0/23 (0%)		2/25 (8%)
Infection-other	0/23 (0%)		1/25 (4%)
Injury, poisoning and procedural complications
Chemoradiation dermatitis	0/23 (0%)		1/25 (4%)
Investigations
Alkaline phosphatase	0/23 (0%)		1/25 (4%)
ALT, SGPT	0/23 (0%)		1/25 (4%)
AST, SGOT	0/23 (0%)		2/25 (8%)
Bilirubin	0/23 (0%)		1/25 (4%)
Leukocytes	3/23 (13%)		5/25 (20%)
Metabolic/Laboratory-other	0/23 (0%)		1/25 (4%)
Neutrophils	1/23 (4.3%)		5/25 (20%)
Platelets	5/23 (21.7%)		1/25 (4%)
Weight loss	0/23 (0%)		1/25 (4%)
Metabolism and nutrition disorders
Anorexia	2/23 (8.7%)		5/25 (20%)
Bicarbonate	1/23 (4.3%)		0/25 (0%)
Dehydration	0/23 (0%)		1/25 (4%)
Hyperglycemia	4/23 (17.4%)		2/25 (8%)
Hyperkalemia	1/23 (4.3%)		0/25 (0%)
Hypermagnesemia	0/23 (0%)		1/25 (4%)
Hypernatremia	1/23 (4.3%)		1/25 (4%)
Hypoalbuminemia	0/23 (0%)		1/25 (4%)
Hypoglycemia	1/23 (4.3%)		0/25 (0%)
Hypokalemia	0/23 (0%)		1/25 (4%)
Hypomagnesemia	7/23 (30.4%)		8/25 (32%)
Hyponatremia	2/23 (8.7%)		3/25 (12%)
Musculoskeletal and connective tissue disorders
Arthritis	0/23 (0%)		1/25 (4%)
Bone, pain	0/23 (0%)		1/25 (4%)
Extremity-limb, pain	2/23 (8.7%)		5/25 (20%)
Joint, pain	12/23 (52.2%)		7/25 (28%)
Joint-function	0/23 (0%)		3/25 (12%)
Muscle, pain	6/23 (26.1%)		4/25 (16%)
Musculoskeletal/soft tissue-other	0/23 (0%)		2/25 (8%)
Neck, pain	2/23 (8.7%)		0/25 (0%)
Nonneuropathic generalized weakness	0/23 (0%)		1/25 (4%)
Nonneuropathic upper extr muscle weak	0/23 (0%)		2/25 (8%)
Nervous system disorders
Dizziness	1/23 (4.3%)		1/25 (4%)
Head/headache	6/23 (26.1%)		4/25 (16%)
Neurologic-other	1/23 (4.3%)		0/25 (0%)
Neuropathy-motor	2/23 (8.7%)		3/25 (12%)
Neuropathy-sensory	14/23 (60.9%)		12/25 (48%)
Sinus, pain	1/23 (4.3%)		0/25 (0%)
Taste disturbance	1/23 (4.3%)		3/25 (12%)
Psychiatric disorders
Anxiety	5/23 (21.7%)		2/25 (8%)
Confusion	0/23 (0%)		1/25 (4%)
Depression	1/23 (4.3%)		0/25 (0%)
Insomnia	2/23 (8.7%)		1/25 (4%)
Libido	0/23 (0%)		1/25 (4%)
Renal and urinary disorders
Bladder, pain	0/23 (0%)		1/25 (4%)
Proteinuria	4/23 (17.4%)		2/25 (8%)
Renal/GU-other	1/23 (4.3%)		1/25 (4%)
Urinary frequency/urgency	1/23 (4.3%)		1/25 (4%)
Urinary hemorrhage NOS	1/23 (4.3%)		0/25 (0%)
Reproductive system and breast disorders
Vagina, hemorrhage	2/23 (8.7%)		1/25 (4%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	1/23 (4.3%)		2/25 (8%)
Cough	1/23 (4.3%)		0/25 (0%)
Dyspnea	2/23 (8.7%)		0/25 (0%)
Nose, hemorrhage	13/23 (56.5%)		7/25 (28%)
Pulmonary/Upper Respiratory-other	0/23 (0%)		1/25 (4%)
Throat/pharynx/larynax, pain	1/23 (4.3%)		0/25 (0%)
Voice changes/dysarthria	2/23 (8.7%)		3/25 (12%)
Skin and subcutaneous tissue disorders
Alopecia	12/23 (52.2%)		11/25 (44%)
Dry skin	1/23 (4.3%)		11/25 (44%)
Erythema multiforme	0/23 (0%)		1/25 (4%)
Hand-foot reaction	0/23 (0%)		1/25 (4%)
Nail changes	0/23 (0%)		3/25 (12%)
Photosensitivity	0/23 (0%)		1/25 (4%)
Pruritus/itching	1/23 (4.3%)		5/25 (20%)
Rash/desquamation	1/23 (4.3%)		8/25 (32%)
Rash: acne/acneiform	1/23 (4.3%)		16/25 (64%)
Skin breakdown/decubitus ulcer	0/23 (0%)		1/25 (4%)
Skin, pain	0/23 (0%)		1/25 (4%)
Skin-other	0/23 (0%)		4/25 (16%)
Urticaria	1/23 (4.3%)		0/25 (0%)
Vascular disorders
Hemorrhage-other	1/23 (4.3%)		0/25 (0%)
Hypertension	9/23 (39.1%)		9/25 (36%)
Hypotension	0/23 (0%)		1/25 (4%)

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.