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Atezolizumab and Bevacizumab in Rare Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03074513
Recruitment Status : Recruiting
First Posted : March 8, 2017
Last Update Posted : January 9, 2019
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

The goal of this clinical research study is to learn if atezolizumab and bevacizumab can help to control rare solid tumors.

This is an investigational study. Atezolizumab is FDA approved and commercially available for the treatment of metastatic (has spread) non-small cell lung cancer (NSCLC).

Bevacizumab is FDA approved and commercially available for the treatment of metastatic colorectal cancer, metastatic non-squamous NSCLC, metastatic renal cell carcinoma, recurrent (has come back after treatment) glioblastoma, cervical cancer, and platinum-resistant (a type of chemotherapy) recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer.

The combination of these drugs to treat the type of cancer you have is considered investigational. The study doctor can explain how the study drugs are designed to work.

Up to 160 participants will be enrolled in this study. All will take part at MD Anderson.


Condition or disease Intervention/treatment Phase
Malignant Neoplasms of Digestive Organs Malignant Neoplasms of Lip Oral Cavity and Pharynx Malignant Neoplasms of Mesothelial and Soft Tissue Malignant Neoplasms of Respiratory and Intrathoracic Organs Drug: Atezolizumab Drug: Bevacizumab Behavioral: Phone Call Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 160 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II, Single-Arm Open-Label Study Of The Combination Of Atezolizumab And Bevacizumab In Rare Solid Tumors
Actual Study Start Date : March 3, 2017
Estimated Primary Completion Date : March 2021
Estimated Study Completion Date : March 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Appendiceal Adenocarcinoma, KRAS-Wild Type

Participants receive Atezolizumab and Bevacizumab on Day 1 of each cycle.

Each cycle is 21 days.

Participant may continue taking the study drugs for as long as the doctor thinks it is in their best interest.

About every 3 months after end-of-treatment visit, participant or caregiver called by study staff.

Drug: Atezolizumab
1200 mg by vein on Day 1 of each 21-day cycle. Atezolizumab administered prior to Bevacizumab, with a minimum of 5 minutes between dosing.
Other Name: MPDL3280A

Drug: Bevacizumab
15 mg/kg by vein every 3 weeks on Day 1 of each 21-day cycle.
Other Names:
  • Avastin
  • Anti-VEGF monoclonal antibody
  • rhuMAb-VEGF

Behavioral: Phone Call
About every 3 months after end-of-treatment visit, participant or caregiver called by study staff.

Experimental: Epstein-Barr Virus-Associated Nasopharyngeal Carcinoma

Participants receive Atezolizumab and Bevacizumab on Day 1 of each cycle.

Each cycle is 21 days.

Participant may continue taking the study drugs for as long as the doctor thinks it is in their best interest.

About every 3 months after end-of-treatment visit, participant or caregiver called by study staff.

Drug: Atezolizumab
1200 mg by vein on Day 1 of each 21-day cycle. Atezolizumab administered prior to Bevacizumab, with a minimum of 5 minutes between dosing.
Other Name: MPDL3280A

Drug: Bevacizumab
15 mg/kg by vein every 3 weeks on Day 1 of each 21-day cycle.
Other Names:
  • Avastin
  • Anti-VEGF monoclonal antibody
  • rhuMAb-VEGF

Behavioral: Phone Call
About every 3 months after end-of-treatment visit, participant or caregiver called by study staff.

Experimental: Human Papilloma Virus-Associated Cancers

Participants receive Atezolizumab and Bevacizumab on Day 1 of each cycle.

Each cycle is 21 days.

Participant may continue taking the study drugs for as long as the doctor thinks it is in their best interest.

About every 3 months after end-of-treatment visit, participant or caregiver called by study staff.

Drug: Atezolizumab
1200 mg by vein on Day 1 of each 21-day cycle. Atezolizumab administered prior to Bevacizumab, with a minimum of 5 minutes between dosing.
Other Name: MPDL3280A

Drug: Bevacizumab
15 mg/kg by vein every 3 weeks on Day 1 of each 21-day cycle.
Other Names:
  • Avastin
  • Anti-VEGF monoclonal antibody
  • rhuMAb-VEGF

Behavioral: Phone Call
About every 3 months after end-of-treatment visit, participant or caregiver called by study staff.

Experimental: Merkel Cell Carcinoma

Participants receive Atezolizumab and Bevacizumab on Day 1 of each cycle.

Each cycle is 21 days.

Participant may continue taking the study drugs for as long as the doctor thinks it is in their best interest.

About every 3 months after end-of-treatment visit, participant or caregiver called by study staff.

Drug: Atezolizumab
1200 mg by vein on Day 1 of each 21-day cycle. Atezolizumab administered prior to Bevacizumab, with a minimum of 5 minutes between dosing.
Other Name: MPDL3280A

Drug: Bevacizumab
15 mg/kg by vein every 3 weeks on Day 1 of each 21-day cycle.
Other Names:
  • Avastin
  • Anti-VEGF monoclonal antibody
  • rhuMAb-VEGF

Behavioral: Phone Call
About every 3 months after end-of-treatment visit, participant or caregiver called by study staff.

Experimental: Neuroendocrine Tumors, Pancreatic

Participants receive Atezolizumab and Bevacizumab on Day 1 of each cycle.

Each cycle is 21 days.

Participant may continue taking the study drugs for as long as the doctor thinks it is in their best interest.

About every 3 months after end-of-treatment visit, participant or caregiver called by study staff.

Drug: Atezolizumab
1200 mg by vein on Day 1 of each 21-day cycle. Atezolizumab administered prior to Bevacizumab, with a minimum of 5 minutes between dosing.
Other Name: MPDL3280A

Drug: Bevacizumab
15 mg/kg by vein every 3 weeks on Day 1 of each 21-day cycle.
Other Names:
  • Avastin
  • Anti-VEGF monoclonal antibody
  • rhuMAb-VEGF

Behavioral: Phone Call
About every 3 months after end-of-treatment visit, participant or caregiver called by study staff.

Experimental: Neuroendocrine Tumors, Extrapancreatic

Participants receive Atezolizumab and Bevacizumab on Day 1 of each cycle.

Each cycle is 21 days.

Participant may continue taking the study drugs for as long as the doctor thinks it is in their best interest.

About every 3 months after end-of-treatment visit, participant or caregiver called by study staff.

Drug: Atezolizumab
1200 mg by vein on Day 1 of each 21-day cycle. Atezolizumab administered prior to Bevacizumab, with a minimum of 5 minutes between dosing.
Other Name: MPDL3280A

Drug: Bevacizumab
15 mg/kg by vein every 3 weeks on Day 1 of each 21-day cycle.
Other Names:
  • Avastin
  • Anti-VEGF monoclonal antibody
  • rhuMAb-VEGF

Behavioral: Phone Call
About every 3 months after end-of-treatment visit, participant or caregiver called by study staff.

Experimental: Peritoneal Mesothelioma

Participants receive Atezolizumab and Bevacizumab on Day 1 of each cycle.

Each cycle is 21 days.

Participant may continue taking the study drugs for as long as the doctor thinks it is in their best interest.

About every 3 months after end-of-treatment visit, participant or caregiver called by study staff.

Drug: Atezolizumab
1200 mg by vein on Day 1 of each 21-day cycle. Atezolizumab administered prior to Bevacizumab, with a minimum of 5 minutes between dosing.
Other Name: MPDL3280A

Drug: Bevacizumab
15 mg/kg by vein every 3 weeks on Day 1 of each 21-day cycle.
Other Names:
  • Avastin
  • Anti-VEGF monoclonal antibody
  • rhuMAb-VEGF

Behavioral: Phone Call
About every 3 months after end-of-treatment visit, participant or caregiver called by study staff.

Experimental: Pleural Mesothelioma

Participants receive Atezolizumab and Bevacizumab on Day 1 of each cycle.

Each cycle is 21 days.

Participant may continue taking the study drugs for as long as the doctor thinks it is in their best interest.

About every 3 months after end-of-treatment visit, participant or caregiver called by study staff.

Drug: Atezolizumab
1200 mg by vein on Day 1 of each 21-day cycle. Atezolizumab administered prior to Bevacizumab, with a minimum of 5 minutes between dosing.
Other Name: MPDL3280A

Drug: Bevacizumab
15 mg/kg by vein every 3 weeks on Day 1 of each 21-day cycle.
Other Names:
  • Avastin
  • Anti-VEGF monoclonal antibody
  • rhuMAb-VEGF

Behavioral: Phone Call
About every 3 months after end-of-treatment visit, participant or caregiver called by study staff.




Primary Outcome Measures :
  1. Overall Response Rate of Atezolizumab in Combination with Bevacizumab [ Time Frame: 12 weeks ]
    Response determined by an independent radiologist according to RECIST v1.1.


Secondary Outcome Measures :
  1. Adverse Events of Atezolizumab in Combination with Bevacizumab [ Time Frame: 6 months ]
    Occurrence and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Signed Informed Consent Form
  2. Age >/= 18 years
  3. Ability to comply with the study protocol, in the investigator's judgment
  4. Measurable disease according to RECIST v1.1. Previously irradiated lesions can be considered as measurable disease only if progressive disease has been unequivocally documented at that site since radiation. The pleural mesothelioma cohort will require measurable disease according to modified RECIST as specified in the appended manuscript.
  5. ECOG Performance Status of 0 or 1
  6. Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to initiation of study treatment: ANC >/= 1.5 x 10(9)/L without granulocyte colony-stimulating factor support; Lymphocyte count >/= 0.5 x 10(9)/L; Platelet count >/= 100 x 10(9)/L without transfusion; WBC Count >/= 2500/ul; Hemoglobin >/= 90 g/L [Patients may be transfused to meet this criterion]; AST, ALT, and alkaline phosphatase (ALP) </= 2.5 x upper limit of normal (ULN), with the following exceptions: Patients with documented liver metastases: AST and ALT </= 5 x ULN Patients with documented liver or bone metastases: ALP </= 5 x ULN - Serum bilirubin ≤ 1.5 x ULN - Serum creatinine </= 1.5 x ULN - Serum albumin >/= 2.5 g/dL - For patients not receiving therapeutic anticoagulation: INR or aPTT </= 1.5 x ULN
  7. For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
  8. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of < 1% per year during the treatment period and for 6 months after the last dose of study treatment.
  9. (cont.) A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (>/= 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). Examples of contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.
  10. Appendiceal adenocarcinoma basket

    1. Metastatic appendiceal adenocarcinoma
    2. Not considered candidate for curative surgery
  11. Nasopharyngeal carcinoma basket a. Metastatic or locally recurrent disease not amenable to curative intent treatment b. Any number of prior therapies, including 0
  12. Human Papilloma Virus-associated cancers a. Histologically proven squamous carcinoma of the anal canal, penile, vaginal, vulva, or refractory cervical cancer with progression or intolerance to at least one treatment regimen including cisplatin or carboplatin will be enrolled. HPV confirmation is not required. b. Patients must have metastatic disease not amenable to surgical resection. c. If HIV+ positive, all patients infected with Human Immunodeficiency Virus (HIV) and CD4+ T cell count > 400 cells/mm3 may be eligible for study. d. Patients co-infected with hepatitis B virus and/or hepatitis C virus may be included in this study provided that their liver function tests remain within the limits listed above. Patients must be followed by a hepatologist during the course of this study.
  13. Merkel Cell Carcinoma basket a. Metastatic or locally recurrent disease not amenable to curative intent treatment b. Any number of prior therapies, including 0
  14. Neuroendocrine tumors, pancreatic basket a. Grade 1 or grade 2 (or described as low grade, intermediate grade, well differentiated, or moderately differentiated) according to reviewing pathologist b. Progressive disease over the preceding 12 months c. Any number of prior therapies, including 0 d. Patients using a somatostatin analogue for symptom control must be on stable doses for 56 days prior to enrollment.
  15. Neuroendocrine tumors, extrapancreatic basket a. Grade 1 or grade 2 (or described as low grade, intermediate grade, well differentiated, or moderately differentiated; typical or atypical carcinoid if originating in lung) according to reviewing pathologist b. Progressive disease over the preceding 12 months c. Any number of prior therapies, including 0 d. Patients using a somatostatin analogue for symptom control must be on stable doses for 56 days prior to enrollment.
  16. Peritoneal mesothelioma basket a. Refractory or intolerant to platinum and pemetrexed systemic therapy b. Any number of prior therapies
  17. Pleural mesothelioma basket

    1. Metastatic or locally recurrent disease not amenable to curative intent treatment
    2. Refractory to platinum and pemetrexed systemic therapy
    3. Any number of prior therapies

Exclusion Criteria:

  1. Treatment for the studied cancer within 28 days prior to initiation of study treatment
  2. Treatment with investigational therapy within 28 days prior to initiation of study treatment
  3. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
  4. Known hypersensitivity to biopharmaceutical agents produced in Chinese hamster ovary cells
  5. Known allergy or hypersensitivity to any component of the atezolizumab formulation
  6. Known allergy or hypersensitivity to any component of the bevacizumab formulation
  7. Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, or multiple sclerosis, with the following exceptions:
  8. (cont.) Patients with a history of autoimmune-related hypothyroidism who are on thyroid replacement hormone are eligible for the study.

    Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.

    Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:

    • Rash must cover < 10% of body surface area
    • Disease is well controlled at baseline and requires only low-potency topical corticosteroids
    • No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high potency or oral corticosteroids within the previous 12 months
  9. Prior allogeneic stem cell or solid organ transplantation
  10. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan.

    (History of radiation pneumonitis in the radiation field (fibrosis) is permitted)

  11. Positive HIV test at screening (except in cohort 3, HPV-associated cancers)
  12. Except in cohort 3, HPV-associated cancers, active hepatitis B virus (HBV) infection (chronic or acute), defined as having a positive hepatitis B surface antigen (HBsAg) test at screening. Patients with a past or resolved HBV infection, defined as having a negative HBsAg test and a positive total hepatitis B core antibody (HBcAb) test and negative HBV DNA test at screening, are eligible for the study.
  13. Except in cohort 3, HPV-associated cancers active hepatitis C virus (HCV) infection, defined as having a positive HCV antibody test followed by a positive HCV RNA test at screening.

    The HCV RNA test will be performed only for patients who have a positive HCV antibody test.

  14. Active tuberculosis
  15. Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
  16. Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment.

    Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.

  17. Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction, or cerebrovascular accident within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
  18. Major surgical procedure other than for diagnosis within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the course of the study
  19. Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during the course of the study, or up to 5 months following the anticipated last dose of atezolizumab.
  20. Malignancies other than the disease under study within 5 years prior to Cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death and with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, or ductal carcinoma in situ treated surgically with curative intent) or undergoing active surveillance per standard-of-care management (e.g., chronic lymphocytic leukemia Rai Stage 0)
  21. Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
  22. Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
  23. Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 [IL-2]) within 4 weeks or five half-lives of the drug (whichever is longer) prior to initiation of study treatment
  24. Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF-α agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during the course of the study, with the following exceptions:

    Patients who received low-dose immunosuppressant medication are eligible for the study.

    Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study.

  25. Pregnant or breastfeeding, or intending to become pregnant during the study. Women of childbearing potential must have a negative serum pregnancy test result within 14 days prior to initiation of study treatment.
  26. Inadequately controlled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure > 100 mmHg).

    Anti-hypertensive therapy to maintain a systolic blood pressure <150 mmHg and/or diastolic blood pressure < 100 mmHg is permitted.

  27. Prior history of hypertensive crisis or hypertensive encephalopathy
  28. History of stroke or transient ischemic attack within 6 months prior to Cycle 1, Day 1
  29. Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Cycle 1, Day 1
  30. Patients with a baseline ECG demonstrating a QTc > 460 ms
  31. Evidence of bleeding diathesis or clinically significant coagulopathy (in the absence of therapeutic anticoagulation)
  32. Current or recent (within 10 calendar days prior to Cycle 1, Day 1) use of dipyramidole, ticlopidine, clopidogrel, or cilostazol
  33. Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 calendar days prior to the first dose of bevacizumab
  34. History of abdominal or tracheoesophageal fistula or gastrointestinal perforation within 6 months prior to Cycle 1, Day 1
  35. Clinical signs or symptoms of gastrointestinal obstruction or requirement for routine parenteral hydration, parenteral nutrition, or tube feeding
  36. Evidence of abdominal free air not explained by paracentesis or recent surgical procedure
  37. Serious, non-healing or dehiscing wound, active ulcer, or untreated bone fracture
  38. Proteinuria, as demonstrated by urine dipstick or > 1.0 g of protein in a 24-hour urine collection. All patients with >/= 2+ protein on dipstick urinalysis at baseline must undergo a 24-hour urine collection for protein.
  39. Appendiceal adenocarcinoma basket

    1. Complete or partial bowel obstruction
  40. Epstein-Barr Virus-associated nasopharyngeal carcinoma basket.

  41. Human Papilloma Virus-associated cancers basket

    a. None

  42. Merkel Cell Carcinoma basket

    a. none

  43. Neuroendocrine tumors, pancreatic basket

    1. Grade 3, poorly differentiated neuroendocrine carcinoma
    2. Large cell or small cell histology
  44. Neuroendocrine tumors, extrapancreatic basket

    1. Grade 3, poorly differentiated neuroendocrine carcinoma
    2. Large cell or small cell histology
  45. Peritoneal mesothelioma basket

    a. None

  46. Pleural mesothelioma basket a. None

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03074513


Contacts
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Contact: Daniel M. Halperin, MD 713-792-2828 dmhalperin@mdanderson.org

Locations
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United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Clinical Research Operations       dmhalperin@mdanderson.org   
Sponsors and Collaborators
M.D. Anderson Cancer Center
Genentech, Inc.
Investigators
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Principal Investigator: Daniel M. Halperin, MD M.D. Anderson Cancer Center

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT03074513     History of Changes
Other Study ID Numbers: 2016-0861
NCI-2017-00501 ( Registry Identifier: NCI CTRP )
First Posted: March 8, 2017    Key Record Dates
Last Update Posted: January 9, 2019
Last Verified: January 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by M.D. Anderson Cancer Center:
Malignant neoplasms of digestive organs
Malignant neoplasms of lip oral cavity and pharynx
Malignant neoplasms of mesothelial and soft tissue
Malignant neoplasms of respiratory and intrathoracic organs
Rare Solid Tumors
Atezolizumab
MPDL3280A
Bevacizumab
Avastin
Anti-VEGF monoclonal antibody
rhuMAb-VEGF
Phone call

Additional relevant MeSH terms:
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Neoplasms
Lip Neoplasms
Mouth Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Lip Diseases
Mouth Diseases
Stomatognathic Diseases
Bevacizumab
Atezolizumab
Antibodies
Antibodies, Monoclonal
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Immunologic Factors