A Study of the Safety and Efficacy of Atezolizumab Administered in Combination With Bevacizumab and/or Other Treatments in Participants With Solid Tumors
Status: | Recruiting |
---|---|
Conditions: | Cancer |
Therapuetic Areas: | Oncology |
Healthy: | No |
Age Range: | 18 - Any |
Updated: | 4/4/2019 |
Start Date: | April 6, 2016 |
End Date: | January 28, 2021 |
Contact: | Reference Study ID Number: GO30140 www.roche.com/about_roche/roche_worldwide.htm |
Email: | global-roche-genentech-trials@gene.com |
Phone: | 888-662-6728 (U.S. and Canada) |
An Open-Label, Multicenter Phase Ib Study of The Safety and Efficacy of Atezolizumab (Anti-PD-L1 Antibody) Administered in Combination With Bevacizumab and/or Other Treatments in Patients With Solid Tumors
This study will evaluate the safety, efficacy, and pharmacokinetics of atezolizumab in
combination with bevacizumab, bevacizumab + oxaliplatin, leucovorin and 5-fluorouracil (5-FU)
(FOLFOX), vanucizumab, nab-paclitaxel + gemcitabine, FOLFOX, or 5-FU + cisplatin, in
participants with solid tumors.
combination with bevacizumab, bevacizumab + oxaliplatin, leucovorin and 5-fluorouracil (5-FU)
(FOLFOX), vanucizumab, nab-paclitaxel + gemcitabine, FOLFOX, or 5-FU + cisplatin, in
participants with solid tumors.
Inclusion Criteria:
General Inclusion criteria
- Measurable disease per RECIST v1.1
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Adequate hematologic and end organ function
- Resolution of any acute, clinically significant treatment-related toxicity from prior
therapy to Grade less than or equal to (=) 1 prior to study entry, with the
exception of alopecia
- Ready to use reliable contraceptive procedures
Inclusion Criteria Specific to HCC (Arm A and Arm F):
- Participants with advanced or metastatic and/or unresectable HCC
- The participant has disease that is not amenable to a curative approach
- No prior line of systemic therapy (includes participants who are sorafenib-naïve)
- Willing to undergo fresh liver biopsy if provided archival tissue was taken greater
than (>) 6 months from Cycle 1 Day 1
- Child-Pugh Score of up to B7
- Serum bilirubin = 3 times upper limit of normal (x ULN)
- International normalized ratio (INR) and activated partial thromboplastin time (aPTT)
= 2 x ULN
- Albumin >2.8 grams per deciliter (g/dL)
- Documented virology status of hepatitis, as confirmed by screening hepatitis B surface
antigen (HBsAg), antibody to hepatitis B core antigen (anti-HBc), and/or
anti-hepatitis C virus (anti-HCV)
- Antiviral therapy per local standard-of-care if active hepatitis B virus (HBV)
Inclusion Criteria Specific to Arm A (Patients must also meet all of the following specific
inclusion criteria to be eligible for enrollment in Arm A:)
- Child-Pugh score of up to B7
- Willing to undergo biopsy if archival tissue is not available or if archival tissue
was taken >6 months from Cycle 1, Day 1
- Anti-viral therapy per local standard-of-care if active hepatitis B virus (HBV).
Inclusion Criteria Specific to Arm F (Patients must also meet all of the following specific
inclusion criteria to be eligible for enrollment in Arm F:)
- LIfe expectancy >=3 months, as determined by the investigator
- Child-Pugh score A
- Platelet count ≥ 75x109/L (75,000/uL) without transfusion
- Availability at the site of tumor specimens in paraffin blocks (preferred) or 16
unstained slides, with an associated pathology report, prior to study entry
- Anti-viral therapy per local standard-of-care if active hepatitis B virus (HBV).
Inclusion Criteria Specific to Gastric Cancer (Arm B) (Patients must also meet all of the
following specific inclusion criteria to be eligible for enrollment in Arm B:)
- Histologically or cytologically confirmed locally advanced or metastatic
adenocarcinoma of the stomach or GEJ in participants who have not received prior
systemic therapy for metastatic disease
- Absence of HER2 expression documented as in situ hybridization (ISH) negative on
previously collected and assessed tumor tissue upon initial diagnosis of disease
Inclusion criteria specific to metastatic pancreatic cancer (Arm C) (Patients must also
meet all of the following specific inclusion criteria to be eligible for enrollment in Arm
C:)
- Histologically or cytologically confirmed metastatic adenocarcinoma of the pancreas
- No previous radiotherapy, surgery, chemotherapy, or investigational therapy for the
treatment of metastatic disease
Inclusion Criteria Specific to mEC (Arm E) (Patients must also meet all of the following
specific inclusion criteria to be eligible for enrollment in Arm E:)
- Histologically or cytologically confirmed locally mEC or metastatic adenocarcinoma of
the GEJ Siewert Classification Type I in participants who have not received prior
systemic therapy for primary and metastatic disease or chemoradiation therapy for
primary disease
- Absence of HER2 expression documented as ISH-negative on previously collected and
assessed tumor tissue upon initial diagnosis of disease
- Willing to undergo biopsy if archival tissue is not available or if archival tissue
was taken >6 months from Cycle 1 Day 1
Exclusion Criteria:
General Exclusion Criteria
- Uncontrolled pleural effusion, pericardial effusion, or ascites
- Uncontrolled tumor-related pain
- Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of
bisphosphonate therapy
- Known clinically significant liver disease, including active viral, alcoholic, or
other hepatitis, cirrhosis, fatty liver, and inherited liver disease (exception for
participants in Arm A and Arm F)
- Known primary central nervous system (CNS) malignancy or untreated or active CNS
metastases
- Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells
or other recombinant human antibodies
- Positive test for Human Immunodeficiency Virus (HIV)
- Active hepatitis B (chronic or acute), or hepatitis C (exception for participants in
Arm A and Arm F)
- Active tuberculosis
- Severe infections within 4 weeks prior to Day 1
- Signs or symptoms of significant infection within 2 weeks prior to Day 1
- Received oral or IV antibiotics within 2 weeks prior to Cycle 1 Day 1
- Significant cardiovascular disease, such as New York Heart Association (NYHA) cardiac
disease (Class II or greater), myocardial infarction within 3 months prior to Day 1,
unstable arrhythmias, or unstable angina
- History of stroke, reversible ischemic neurological defect or transient ischemic
attack within 6 months prior to Day 1
- Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1 or
anticipation that such a live attenuated vaccine will be required during the study
- Any serious medical condition or abnormality in clinical laboratory tests that, in the
investigator's and/or Medical Monitor's judgment, precludes the participants safe
participation in and completion of the study
- Malignancies other than pancreatic carcinoma within 2 years prior to study start, with
the exception of those with a negligible risk of metastasis or death treated with
expected curative outcome (such as adequately treated carcinoma in situ of the cervix,
basal or squamous cell skin cancer, localized prostate cancer treated surgically with
curative intent, ductal carcinoma in situ treated surgically with curative intent)
Exclusion Criteria Related to Medications
- Prior treatment with anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA4),
anti-programmed death-1 (anti-PD-1), or anti-programmed death ligand-1 (anti-PD-L1)
therapeutic antibody
- Treatment with systemic immunostimulatory agents within 6 weeks or five half-lives of
the drug, whichever is longer, prior to screening
- Treatment with systemic corticosteroids or other immunosuppressive medications within
2 weeks prior to Cycle 1, Day 1
- History of severe allergic, anaphylactic, or other hypersensitivity reactions to
chimeric or humanized antibodies or fusion proteins
- Participants with prior allogeneic bone marrow transplantation or prior solid organ
transplantation
- Known allergies to oxaliplatin (or other platinum agents), leucovorin, 5-FU,
nab-paclitaxel (or other taxanes) or gemcitabine
Exclusion Criteria Specific to Bevacizumab-Containign Arms (Arms A, B, and F) (Patients who
meet any of the following criteria will be excluded from enrollment into
bevacizumab-containing Arms A, B, and F:)
- Core biopsy or other minor surgical procedure, excluding placement of a vascular
access device, within 3 days prior to the first dose of bevacizumab or vanucizumab
- History of abdominal or tracheoesophageal fistula, gastrointestinal (GI) perforation,
or intra-abdominal abscess within 6 months prior to Day 1
- History of intestinal obstruction and/or clinical signs or symptoms of GI obstruction
within 6 months prior to Day 1 of Cycle 1
- Clinical signs or symptoms of GI obstruction or requirement for routine parenteral
hydration, parenteral nutrition, or tube feeding
- Evidence of abdominal free air that is not explained by paracentesis or recent
surgical procedure
- Serious, non-healing or dehiscing wound, active ulcer, or untreated bone fracture
- Proteinuria, as demonstrated by urine dipstick or > 1.0 g of protein in a 24-hour
urine collection
- Metastatic disease that involves major airways or blood vessels, or centrally located
mediastinal tumor masses of large volume. HCC participants (Arm A and F) with vascular
invasion of the portal or hepatic veins may be enrolled
- History of intra-abdominal inflammatory process within 6 months prior to Day 1 of
Cycle 1
- Radiotherapy within 28 days and abdominal/pelvic radiotherapy within 60 days prior to
Day 1 of Cycle 1
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to Day 1 of Cycle 1
- Chronic daily treatment with a nonsteroidal anti-inflammatory drug (NSAID)
Exclusions specific to Arms A and F (HCC) (Patients who meet any of the following specific
exclusion criteria will be excluded from enrollment in Arms A and F:)
- Participants with untreated or incompletely treated varices with bleeding or high-risk
for bleeding
- Treatment with any HCV anti-viral therapy within 4 weeks prior to Cycle 1 Day 1
- Moderate or severe ascites
- Hepatic encephalopathy
Exclusion Criteria Specific to Arm B (Gastric Cancer) (Patients who meet any of the
following specific exclusion criteria will be excluded from enrollment in Arm B:)
- HER2 expression as defined by ISH positive and/or 3+ by immunohistochemistry (IHC)
- Prior treatment with an oxaliplatin-containing regimen
- Previous antiangiogenic therapy
- Ongoing treatment for epilepsy
Exclusion Criteria Specific to Arm C (Metastatic Pancreatic Cancer) (Patients who meet any
of the following specific exclusion criteria will be excluded from enrollment in Arm C:)
- Patients with only locally advanced disease
- Presence of islet cell neoplasms
Exclusions Specific to Arm E (Metastatic Esophageal Cancer) (Patients who meet any of the
following specific exclusion criteria will be excluded from enrollment in Arm E:)
- HER2 expression as defined by ISH positive and/or 3+ by immunohistochemistry
- Prior chemotherapy treatment, including radio-sensitization in pre- and post-operative
settings
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University of Colorado Hospital, Site Top medical professionals, superior medicine and progressive change make University...
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Dana-Farber Cancer Institute Since it’s founding in 1947, Dana-Farber has been committed to providing adults...
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Duke Cancer Institute Leading-edge cancer care and research have been a hallmark of Duke Medicine...
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Medical College of Wisconsin The Medical College (MCW) of Wisconsin is a major national research...
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Columbia University Medical Center Situated on a 20-acre campus in Northern Manhattan and accounting for...
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3800 Reservoir Rd NW
Washington, District of Columbia 20007
Washington, District of Columbia 20007
(202) 687-7695
Georgetown University Medical Center Georgetown University Medical Center is committed to excellence in research, education...
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