RADBEV: Study of RAD001 and Bevacizumab in Recurrent Ovarian, Peritoneal, and Fallopian Tube Cancer

• Sponsor: University of Pittsburgh (Other)
• Overall Status: Completed
• CT.gov ID: NCT01031381
• Collaborator: Novartis Pharmaceuticals (Industry), Genentech, Inc. (Industry)
• Enrollment: 50
• Location: 1
• Arm: 1
• Duration (Months): 51
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

This study will investigate the efficacy as well as the safety of RAD001 in combination with bevacizumab for recurrent ovarian, peritoneal, and fallopian tube cancer. RAD001 will be taken orally once daily and bevacizumab will be administered once every 14 days. The study will be conducted over a period of about 3 to 4 years.

Condition or Disease	Intervention/Treatment	Phase
Ovarian Cancer; Fallopian Tube Cancer; Primary Peritoneal Carcinoma	Drug: RAD001; Drug: bevacizumab	Phase 2

Detailed Description

In this trial, approximately 50 patients will receive the study drug, RAD001 in combination with bevacizumab (Avastin)chemotherapy. RAD001 will be taken orally once daily and bevacizumab will be administered intravenously once every 14 days. In addition to study treatment, a few blood samples and a sample of the patients tumor from a previous surgery if available will be collected for research.

Study Design

• Study Type: Interventional
• Actual Enrollment: 50 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of RAD001 and Bevacizumab in Recurrent Ovarian, Peritoneal, and Fallopian Tube Cancer An Investigator-initiated, Single-institution Trial at Magee-Womens Hospital
• Study Start Date: Sep 1, 2010
• Actual Primary Completion Date: Jan 1, 2014
• Actual Study Completion Date: Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Other: Rad001/Bevacizumab Patients will receive RAD001 by mouth everyday and Bevacizumab IV every 14 days until clinical progression.	Drug: RAD001; RAD001 10mg is taken orally (by mouth) once daily on a continuous basis. RAD001 is provided in tablet form and should be taken with a big glass of water on an empty stomach or after a low-fat meal.; Other Names: everolimus derivative of rapamycin ; Drug: bevacizumab; bevacizumab will be administered intravenously (IV) once every 14 days.; Other Names: Avastin

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival (PFS) at 6-months [Up to 36 months (data collection period for the cohort); Up to 6 months for participant]

   The percentage of participants who were alive with the disease (cancer) at 6 months after treatment, but whose disease had not worsened/progressed per Response Evaluation Criteria in Solid Tumors (RECIST v1.1).

Secondary Outcome Measures

1. Total Number of Participants Experienced a Response (Complete Response+Partial Response+Stable Disease) [Within 4 weeks (28 days) of study treatment initiation (baseline)]

   The number participants who experienced Complete Response+Partial Response+Stable Disease per Response Evaluation Criteria in Solid Tumors (RECIST v1.1).

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients may or may not have measurable disease. Measurable disease is defined according to RECIST criteria. If the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation was completed.

• Minimum of four weeks since any major surgery, completion of radiation, or completion of all prior systemic anticancer therapy (adequately recovered from the acute toxicities of any prior therapy)

• Fasting serum cholesterol ≤300 mg/dL OR ≤7.75 mmol/L AND fasting triglycerides ≤ 2.5 x ULN.

• Performance status £ 2

• Signed informed consent.

Exclusion Criteria:

• Prior treatment with any investigational drug within the preceding 4 weeks

• Chronic treatment with systemic steroids or another immunosuppressive agent

• Patients should not receive immunization with attenuated live vaccines within one week of study entry or during study period

• Uncontrolled brain or leptomeningeal metastases

• Other malignancies within the past 5 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin.

• Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation

• Uncontrolled diabetes mellitus

• A known history of HIV seropositivity

• Impairment of gastrointestinal function or gastrointestinal disease

• Patients with an active bleeding diathesis or on oral anti-vitamin K medication (except low dose coumadin)

• Women who are pregnant or breast feeding, or women able to conceive and unwilling to practice an effective method of birth control.

• Patients who have received prior treatment with an mTOR inhibitor (sirolimus, temsirolimus, everolimus).

• Patients with a known hypersensitivity to RAD001 (everolimus), other rapamycins (sirolimus, temsirolimus) or excipients, or bevacizumab

• Patients with serious non-healing wound, ulcer, or bone fracture.

• Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Magee-Womens Hospital of UPMC	Pittsburgh	Pennsylvania	United States	15213

Sponsors and Collaborators

• University of Pittsburgh
• Novartis Pharmaceuticals
• Genentech, Inc.

Investigators

• Principal Investigator: Robert Edwards, MD, University of Pittsburgh, Magee-Womens Hospital, Gynecologic Oncology Division

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Robert Edwards, Principal Investigator, University of Pittsburgh
• ClinicalTrials.gov Identifier: NCT01031381
• Other Study ID Numbers: 09-01-RAD001BEV
• First Posted: Dec 14, 2009
• Last Update Posted: Aug 30, 2016
• Last Verified: Jan 1, 2016

• Keywords provided by Robert Edwards, Principal Investigator, University of Pittsburgh: Recurrent; ovarian; fallopian tube; primary peritoneal; cancer; Recurrent ovarian, fallopian tube, primary peritoneal cancer
• Additional relevant MeSH terms: Fallopian Tube Neoplasms; Bevacizumab; Everolimus

Study Results

Participant Flow

Arm/Group Title	RAD001 + Bevacizumab
Arm/Group Description	Patients with recurrent ovarian, peritoneal, and fallopian tube cancer who received RAD001 10 mg/day by mouth and bevacizumab 10 mg/kg intravenously
Period Title: Overall Study
STARTED	59
COMPLETED	50
NOT COMPLETED	9

Baseline Characteristics

Arm/Group Title	RAD001 + Bevacizumab
Arm/Group Description	Patients with recurrent ovarian, peritoneal, and fallopian tube cancer who received RAD001 10 mg/day by mouth and bevacizumab 10 mg/kg intravenously
Overall Participants	50
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	60.5
Sex: Female, Male (Count of Participants)
Female	50 100%
Male	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	1 2%
White	49 98%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival (PFS) at 6-months
Description	The percentage of participants who were alive with the disease (cancer) at 6 months after treatment, but whose disease had not worsened/progressed per Response Evaluation Criteria in Solid Tumors (RECIST v1.1).
Time Frame	Up to 36 months (data collection period for the cohort); Up to 6 months for participant

Outcome Measure Data

Analysis Population Description

Patients with recurrent ovarian, peritoneal, and fallopian tube cancer who received RAD001 10 mg/day by mouth and bevacizumab 10 mg/kg intravenously every 14 days

Arm/Group Title	RAD001 + Bevacizumab
Arm/Group Description	Patients with recurrent ovarian, peritoneal, and fallopian tube cancer who received RAD001 10 mg/day by mouth and bevacizumab 10 mg/kg intravenously.
Measure Participants	50
Number (95% Confidence Interval) [percentage of participants]	28 56%

2. Secondary Outcome

Title	Total Number of Participants Experienced a Response (Complete Response+Partial Response+Stable Disease)
Description	The number participants who experienced Complete Response+Partial Response+Stable Disease per Response Evaluation Criteria in Solid Tumors (RECIST v1.1).
Time Frame	Within 4 weeks (28 days) of study treatment initiation (baseline)

Outcome Measure Data

Analysis Population Description

Patients with recurrent ovarian, peritoneal, and fallopian tube cancer who received RAD001 10 mg/day by mouth and bevacizumab 10 mg/kg intravenously every 14 days + imaging every 8-12 weeks

Arm/Group Title	RAD001 + Bevacizumab
Arm/Group Description	Patients with recurrent ovarian, peritoneal, and fallopian tube cancer who received RAD001 10 mg/day by mouth and bevacizumab 10 mg/kg intravenously
Measure Participants	50
Number [participants]	4 8%

Adverse Events

Arm/Group Title	RAD001 + Bevacizumab
Arm/Group Description	Patients with recurrent ovarian, peritoneal, and fallopian tube cancer who received RAD001 10 mg/day by mouth and bevacizumab 10 mg/kg intravenously
All Cause Mortality
	RAD001 + Bevacizumab
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	RAD001 + Bevacizumab
	Affected / at Risk (%)	# Events
Total	19/50 (38%)
Cardiac disorders
Cardiac General - Other (Specify, __)	1/50 (2%)
Hypertension	1/50 (2%)
Pericardial effusion (non-malignant)	1/50 (2%)
Gastrointestinal disorders
Dehydration	1/50 (2%)
Diarrhea	1/50 (2%)
Distension/bloating, abdominal	1/50 (2%)
Fistula, GI, Colon/cecum/appendix	1/50 (2%)
Ileus, GI (functional obstruction of bowel, i.e., neuroconstipation)	1/50 (2%)
Mucositis/stomatitis (clinical exam), Oral cavity	2/50 (4%)
Obstruction, GI, Ileum	1/50 (2%)
Obstruction, GI, Small bowel NOS	3/50 (6%)
General disorders
Pain, Abdomen NOS	2/50 (4%)
Pain, Rectum	1/50 (2%)
Hepatobiliary disorders
Liver dysfunction/failure (clinical)	1/50 (2%)
Infections and infestations
Infection with unknown ANC, Lung (pneumonia)	2/50 (4%)
Infection with unknown ANC, Urinary tract NOS	1/50 (2%)
Musculoskeletal and connective tissue disorders
Muscle weakness, generalized or specific area (not due to neuropathy), Left-sided	1/50 (2%)
Nervous system disorders
Neurology - Other (Specify, __)	1/50 (2%)
Speech impairment (e.g., dysphasia or aphasia)	1/50 (2%)
Renal and urinary disorders
Hemorrhage, GU, Bladder	1/50 (2%)
Respiratory, thoracic and mediastinal disorders
Bronchospasm, wheezing	1/50 (2%)
Hypoxia	1/50 (2%)
Pneumonitis/pulmonary infiltrates	1/50 (2%)
Pulmonary/Upper Respiratory - Other (Specify, __)	2/50 (4%)
Vascular disorders
Thrombosis/thrombus/embolism	1/50 (2%)
Other (Not Including Serious) Adverse Events
	RAD001 + Bevacizumab
	Affected / at Risk (%)	# Events
Total	50/50 (100%)
Blood and lymphatic system disorders
Blood/Bone Marrow - Other (Specify, __)	1/50 (2%)
Neutrophils/granulocytes (ANC/AGC)	1/50 (2%)
Leukocytes (total WBC)	2/50 (4%)
Lymphopenia	3/50 (6%)
Platelets	4/50 (8%)
Hemoglobin	9/50 (18%)
Edema: head and neck	1/50 (2%)
Lymphatics - Other (Specify, __)	2/50 (4%)
Edema: limb	7/50 (14%)
Cardiac disorders
Supraventricular and nodal arrhythmia, Atrial fibrillation	1/50 (2%)
Supraventricular and nodal arrhythmia, Sinus bradycardia	1/50 (2%)
Cardiac Arrhythmia - Other (Specify, __)	2/50 (4%)
Palpitations	2/50 (4%)
Supraventricular and nodal arrhythmia, Sinus tachycardia	3/50 (6%)
Hypertension	17/50 (34%)
Eye disorders
Ocular/Visual - Other (Specify, __)	1/50 (2%)
Gastrointestinal disorders
Dry mouth/salivary gland (xerostomia)	1/50 (2%)
Esophagitis	1/50 (2%)
Fistula, GI, Colon/cecum/appendix	1/50 (2%)
Gastritis (including bile reflux gastritis)	1/50 (2%)
Mucositis/stomatitis (clinical exam), Larynx	1/50 (2%)
Proctitis	1/50 (2%)
Ascites (non-malignant)	2/50 (4%)
Hemorrhoids	2/50 (4%)
Mucositis/stomatitis (clinical exam), Anus	2/50 (4%)
Mucositis/stomatitis (clinical exam), Rectum	2/50 (4%)
Taste alteration (dysgeusia)	2/50 (4%)
Flatulence	3/50 (6%)
Heartburn/dyspepsia	3/50 (6%)
Dehydration	4/50 (8%)
Mucositis/stomatitis (functional/symptomatic), Oral cavity	4/50 (8%)
Distension/bloating, abdominal	6/50 (12%)
Gastrointestinal - Other (Specify, __)	7/50 (14%)
Dental: teeth	8/50 (16%)
Constipation	11/50 (22%)
Vomiting	13/50 (26%)
Anorexia	17/50 (34%)
Nausea	20/50 (40%)
Diarrhea	22/50 (44%)
Mucositis/stomatitis (clinical exam), Oral cavity	32/50 (64%)
General disorders
Rigors/chills	2/50 (4%)
Sweating (diaphoresis)	2/50 (4%)
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)	3/50 (6%)
Insomnia	3/50 (6%)
Constitutional Symptoms - Other (Specify, __)	5/50 (10%)
Weight loss	8/50 (16%)
Fatigue (asthenia, lethargy, malaise)	30/50 (60%)
Pain, Anus	1/50 (2%)
Pain, Dental/teeth/peridontal	1/50 (2%)
Pain, Extremity-limb	1/50 (2%)
Pain, Neuralgia/peripheral nerve	1/50 (2%)
Pain, Pelvis	1/50 (2%)
Pain, Rectum	1/50 (2%)
Pain, Stomach	1/50 (2%)
Pain, Urethra	1/50 (2%)
Pain, Vagina	1/50 (2%)
Pain, Bone	3/50 (6%)
Pain, Joint	3/50 (6%)
Pain, Back	4/50 (8%)
Pain, Throat/pharynx/larynx	4/50 (8%)
Pain, Muscle	6/50 (12%)
Pain, Pain NOS	6/50 (12%)
Pain - Other (Specify, __)	11/50 (22%)
Pain, Head/headache	14/50 (28%)
Pain, Abdomen NOS	21/50 (42%)
Vaginal discharge (non-infectious)	2/50 (4%)
Vaginal mucositis	3/50 (6%)
Flu-like syndrome	6/50 (12%)
Immune system disorders
Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)	7/50 (14%)
Infections and infestations
Infection - Other (Specify, __)	1/50 (2%)
Infection (documented) Urinary tract NOS	1/50 (2%)
Infection with normal ANC or Grade 1 or 2 neutrophils, Bladder (urinary)	1/50 (2%)
Infection with normal ANC or Grade 1 or 2 neutrophils, Soft tissue NOS	1/50 (2%)
Infection with normal ANC or Grade 1 or 2 neutrophils, Urinary tract NOS	1/50 (2%)
Infection with unknown ANC, Larynx	1/50 (2%)
Infection with unknown ANC, Oral cavity-gums (gingivitis)	1/50 (2%)
Infection with unknown ANC, Pelvis NOS	1/50 (2%)
Infection with unknown ANC, Bladder (urinary)	2/50 (4%)
Infection with unknown ANC, Bronchus	2/50 (4%)
Infection with unknown ANC, Skin (cellulitis)	2/50 (4%)
Infection with unknown ANC, Upper airway NOS	2/50 (4%)
Infection with unknown ANC, Urinary tract NOS	5/50 (10%)
Investigations
AST, SGOT(serum glutamic oxaloacetic transaminase)	1/50 (2%)
Phosphate, serum-low (hypophosphatemia)	1/50 (2%)
Potassium, serum-high (hyperkalemia)	1/50 (2%)
Creatinine	2/50 (4%)
Metabolic/Laboratory - Other (Specify, __)	2/50 (4%)
Albumin, serum-low (hypoalbuminemia)	3/50 (6%)
Magnesium, serum-low (hypomagnesemia)	3/50 (6%)
Potassium, serum-low (hypokalemia)	4/50 (8%)
Cholesterol, serum-high (hypercholesteremia)	5/50 (10%)
Glucose, serum-high (hyperglycemia)	7/50 (14%)
Triglyceride, serum-high (hypertriglyceridemia)	7/50 (14%)
Musculoskeletal and connective tissue disorders
Arthritis (non-septic)	1/50 (2%)
Muscle weakness, generalized or specific area (not due to neuropathy), Extremity-lower	1/50 (2%)
Muscle weakness, generalized or specific area (not due to neuropathy), Whole body/generalized	5/50 (10%)
Musculoskeletal/Soft Tissue - Other (Specify, __)	7/50 (14%)
Nervous system disorders
Extrapyramidal/involuntary movement/restlessness	1/50 (2%)
Mood alteration, Depression	1/50 (2%)
Neurology - Other (Specify, __)	1/50 (2%)
Syncope (fainting)	1/50 (2%)
Neuropathy: sensory	3/50 (6%)
Dizziness	4/50 (8%)
Mood alteration, Anxiety	6/50 (12%)
Renal and urinary disorders
Cystitis	1/50 (2%)
Fistula, GU, Ureter	1/50 (2%)
Obstruction, GU, Ureter	1/50 (2%)
Bladder spasms	2/50 (4%)
Urinary retention (including neurogenic bladder)	2/50 (4%)
Urinary frequency/urgency	5/50 (10%)
Renal/Genitourinary - Other (Specify, __)	6/50 (12%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion (non-malignant)	1/50 (2%)
Pneumonitis/pulmonary infiltrates	1/50 (2%)
Voice changes/dysarthria (e.g., hoarseness, loss or alteration in voice, laryngitis)	2/50 (4%)
Nasal cavity/paranasal sinus reactions	3/50 (6%)
Pulmonary/Upper Respiratory - Other (Specify, __)	6/50 (12%)
Dyspnea (shortness of breath)	8/50 (16%)
Cough	9/50 (18%)
Skin and subcutaneous tissue disorders
Nail changes	1/50 (2%)
Rash: dermatitis associated with radiation, Chemoradiation	1/50 (2%)
Rash: erythema multiforme (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis)	1/50 (2%)
Urticaria (hives, welts, wheals)	1/50 (2%)
Wound complication, non-infectious	1/50 (2%)
Pruritus/itching	2/50 (4%)
Rash/desquamation	2/50 (4%)
Bruising (in absence of Grade 3 or 4 thrombocytopenia)	3/50 (6%)
Dry skin	4/50 (8%)
Rash: acne/acneiform	5/50 (10%)
Dermatology/Skin - Other (Specify, __)	14/50 (28%)
Vascular disorders
Hematoma	1/50 (2%)
Hemorrhage, GI, Anus	2/50 (4%)
Hemorrhage/Bleeding - Other (Specify, __)	2/50 (4%)
Hemorrhage, pulmonary/upper respiratory, Nose	8/50 (16%)
Phlebitis (including superficial thrombosis)	1/50 (2%)
Thrombosis/embolism (vascular access-related)	1/50 (2%)
Thrombosis/thrombus/embolism	1/50 (2%)
Vascular - Other (Specify, __)	1/50 (2%)

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.