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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05286801




Registration number
NCT05286801
Ethics application status
Date submitted
15/03/2022
Date registered
18/03/2022

Titles & IDs
Public title
Tiragolumab and Atezolizumab for the Treatment of Relapsed or Refractory SMARCB1 or SMARCA4 Deficient Tumors
Scientific title
A Phase 1/2 Study of Tiragolumab (NSC# 827799) and Atezolizumab (NSC# 783608) in Patients With Relapsed or Refractory SMARCB1 or SMARCA4 Deficient Tumors
Secondary ID [1] 0 0
NCI-2022-01992
Secondary ID [2] 0 0
NCI-2022-01992
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Atypical Teratoid/Rhabdoid Tumor 0 0
Epithelioid Sarcoma 0 0
Kidney Medullary Carcinoma 0 0
Malignant Solid Neoplasm 0 0
Poorly Differentiated Chordoma 0 0
Recurrent Atypical Teratoid/Rhabdoid Tumor 0 0
Recurrent Chordoma 0 0
Recurrent Epithelioid Sarcoma 0 0
Recurrent Kidney Medullary Carcinoma 0 0
Recurrent Malignant Solid Neoplasm 0 0
Recurrent Rhabdoid Tumor 0 0
Refractory Atypical Teratoid/Rhabdoid Tumor 0 0
Refractory Chordoma 0 0
Refractory Epithelioid Sarcoma 0 0
Refractory Kidney Medullary Carcinoma 0 0
Refractory Malignant Solid Neoplasm 0 0
Refractory Rhabdoid Tumor 0 0
Rhabdoid Tumor 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Sarcoma (also see 'Bone') - soft tissue
Cancer 0 0 0 0
Bone
Cancer 0 0 0 0
Children's - Other
Cancer 0 0 0 0
Neuroendocrine tumour (NET)
Cancer 0 0 0 0
Thyroid
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Atezolizumab
Treatment: Surgery - Biospecimen Collection
Treatment: Surgery - Computed Tomography
Other interventions - Fludeoxyglucose F-18
Treatment: Surgery - Magnetic Resonance Imaging
Treatment: Surgery - Positron Emission Tomography
Treatment: Other - Tiragolumab
Treatment: Surgery - X-Ray Imaging

Experimental: Arm B (atezolizumab, tiragolumab) - Patients receive atezolizumab IV over 30-60 minutes on day 1 and tiragolumab IV over 30-90 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 5 years in the absence of disease progression or unacceptable toxicity. Patients also undergo standard imaging scans including x-rays, CT, MRI, and/or FDG PET-CT throughout the trial. Patients also undergo blood sample collection on study.

Experimental: Part A (atezolizumab, tiragolumab) - Patients receive tiragolumab IV over 30-90 minutes on day 1 of each cycle and atezolizumab IV over 30-60 minutes on day 1 of each cycle starting in cycle 2. Treatment repeats every 21 days for up to 5 years in the absence of disease progression or unacceptable toxicity. Patients undergo standard imaging scans including x-rays, CT, MRI, and/or FDG PET-CT, throughout the trial. Patients also undergo blood sample collection on study.


Treatment: Other: Atezolizumab
Given IV

Treatment: Surgery: Biospecimen Collection
Undergo blood sample collection

Treatment: Surgery: Computed Tomography
Undergo CT and/or PET-CT

Other interventions: Fludeoxyglucose F-18
Given FDG

Treatment: Surgery: Magnetic Resonance Imaging
Undergo MRI

Treatment: Surgery: Positron Emission Tomography
Undergo PET-CT and/or FDG-PET

Treatment: Other: Tiragolumab
Given IV

Treatment: Surgery: X-Ray Imaging
Undergo x-rays
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Surgery
Intervention code [3] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Frequency of cycle 1 dose limiting toxicities of tiragolumab as monotherapy in pediatric patients
Timepoint [1] 0 0
Up to 21 days
Primary outcome [2] 0 0
Frequency of objective response for the combination of tiragolumab and atezolizumab
Timepoint [2] 0 0
Up to 5 years
Primary outcome [3] 0 0
Frequency of cycle 1 dose limiting toxicities of the combination of tiragolumab and atezolizumab in patients < 12 years
Timepoint [3] 0 0
Up to 21 days
Secondary outcome [1] 0 0
Trough concentration of tiragolumab as monotherapy in cycle 1
Timepoint [1] 0 0
Up to 21 days
Secondary outcome [2] 0 0
Trough concentration for tiragolumab when given in combination with atezolizumab in cycle 2, day 1
Timepoint [2] 0 0
Up to 21 days
Secondary outcome [3] 0 0
Trough concentration for atezolizumab when given in combination tiragolumab with in cycle 3, day 1
Timepoint [3] 0 0
Up to 21 days
Secondary outcome [4] 0 0
Progression free survival (PFS) of the combination therapy for tiragolumab and atezolizumab
Timepoint [4] 0 0
Up to 5 years
Secondary outcome [5] 0 0
Overall survival (OS) of the combination therapy for tiragolumab and atezolizumab
Timepoint [5] 0 0
Up to 5 years
Secondary outcome [6] 0 0
Duration of response of the combination therapy for tiragolumab and atezolizumab
Timepoint [6] 0 0
Up to 5 years

Eligibility
Key inclusion criteria
* Patients must be >= 12 months of age at the time of study enrollment. For part A, patients must be < 18 years old at enrollment. For part B, there is no upper age limit

* The Part B (phase 2) cohorts will initially open concurrently with the part A but will only enroll patients at least 18 years of age. Patients < 18 years of age will be included in the part B cohorts only after the tiragolumab monotherapy dose has been assessed to be safe in the part A portion
* Patients must have SMARCB1 (INI1) or SMARCA4 deficient tumors verified through institutional immunohistochemistry (IHC) or molecular confirmation of a pathologic SMARCB1 (INI1) or SMARCA4 loss or mutation from a Clinical Laboratory Improvement Act (CLIA) certified lab with the following disease histologies:

* Renal medullary carcinoma
* Malignant rhabdoid tumor (extra-CNS)
* Atypical teratoid rhabdoid tumor (CNS)
* Poorly differentiated chordoma
* Epithelioid sarcoma
* Other SMARCB1 or SMARCA4 deficient tumors
* Note: Molecular studies will only be used if IHC is equivocal or cannot be performed. Documentation of the institutional IHC or molecular testing must be uploaded via the RAVE system
* Part A: Patients must have either measurable or evaluable disease Part B: Patients must have either measurable disease per RECIST v1.1 for non-CNS tumors or CNS response criteria for CNS tumors

* Note: See protocol for specific exclusion for patients with CNS primary or metastatic disease
* Patients must have relapsed, refractory disease or newly diagnosed disease for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2 (Karnofsky/Lansky score of >= 50). Use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age. Note: Neurologic deficits in patients with CNS tumors must have been stable for at least 7 days prior to study enrollment. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
* Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the numerical eligibility criteria are met, e.g., blood count criteria, the patient is considered to have recovered adequately

* Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive: See Developmental Therapeutics (DVL) homepage on the Children's Oncology Group (COG) Members site for commercial and investigational agent classifications. For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned Research Coordinator prior to enrollment

* >= 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea). Please refer to the table of myelosuppressive/Anticancer Agents on the COG website: https://www.cogmembers.org/uploadedFiles/Site/Disc/DVL/Documents/TableOfMyelosuppressiveAnti-CancerAgents.pdf
* Anti-cancer agents not known to be myelosuppressive (e.g., not associated with reduced platelet or absolute neutrophil count [ANC] counts): >= 7 days after the last dose of agent. See the DVL homepage on the COG Members site for commercial and investigational agent classifications. For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned Research Coordinator prior to enrollment
* Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1
* Hematopoietic growth factors: >= 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or 7 days for short acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur
* Interleukins, interferons and cytokines (other than hematopoietic growth factors): >= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
* Stem cell infusions (with or without total-body irradiation [TBI]):

* Autologous stem cell infusion including boost infusion: >= 30 days
* Cellular therapy: >= 30 days after the completion of any type of cellular therapy (e.g., modified T cells, natural killer [NK] cells, dendritic cells, etc.)
* External radiation therapy (XRT)/external beam irradiation including protons: >= 14 days after local XRT; >= 90 days after TBI, craniospinal XRT or if radiation to >= 50% of the pelvis; >= 42 days if other substantial bone marrow (BM) radiation
* Radiopharmaceutical therapy (e.g., radiolabeled antibody, iodine I 131 metaiodobenzylguanidine [131I MIBG]): >= 42 days after systemically administered radiopharmaceutical therapy
* Patients must not have had prior TIGIT targeting therapy
* Patients must not have received prior therapy with an anti- PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA4 agent or with an agent directed to another stimulatory or co-inhibitory T cell receptor (i.e. OX-40, CD137)
* Patients must not have received live/attenuated vaccine within 30 days of first dose of treatment
* Patients must not be receiving concomitant systemic steroid medications and >= 14 days must have elapsed since last dose of systemic corticosteroid with the following exceptions:

* The use of physiologic doses of corticosteroids (5 mg/m^2/day up to 10 mg/day of prednisone equivalent) is acceptable
* The use of topical, inhaled, or ophthalmic corticosteroids are acceptable
* The use of acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are acceptable
* Treatment with systemic immunosuppressive medication (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor-alpha [TNF-alpha] agents) must have concluded >= 14 days prior to study enrollment
* For patients with solid tumors without known bone marrow involvement

* Peripheral absolute neutrophil count (ANC) >= 1000/uL (must be performed within 7 days prior to enrollment)
* For patients with solid tumors without known bone marrow involvement

* Platelet count >= 100,000/uL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) (must be performed within 7 days prior to enrollment)
* Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts above (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These patients will not be evaluable for hematologic toxicity
* A creatinine based on age/gender as follows (must be performed within 7 days prior to enrollment):

* Age; Maximum Serum Creatinine (mg/dL)

* 1 to < 2 years; Male: 0.6; Female: 0.6
* 2 to < 6 years; Male: 0.8; Female: 0.8
* 6 to < 10 years; Male: 1; Female: 1
* 10 to < 13 years; Male: 1.2; Female: 1.2
* 13 to < 16 years; Male: 1.5; Female: 1.4
* >= 16 years; Male: 1.7; Female: 1.4 OR- a 24 hour urine creatinine clearance >= 70 mL/min/1.73 m^2 (must be performed within 7 days prior to enrollment) OR- a glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard) (must be performed within 7 days prior to enrollment)
* Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility
* Bilirubin (sum of conjugated + unconjugated or total) =< 1.5 x upper limit of normal (ULN) for age (must be performed within 7 days prior to enrollment)

* Patients with known Gilbert disease: Total bilirubin =< 3 x ULN
* Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L (must be performed within 7 days prior to enrollment). For the purpose of this study, the ULN for SGPT is 45 U/L
* Albumin >= 2 g/dL (must be performed within 7 days prior to enrollment)
* Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled as evidenced by no increase in seizure frequency in the prior 7 days
* Nervous system disorders (Common Terminology Criteria for Adverse Events [CTCAE] v5) resulting from prior therapy must be =< grade 2, with the exception of decreased tendon reflex (DTR). Any grade of DTR is eligible
* International normalized ratio (INR) =< 1.5 (must be performed within 7 days prior to enrollment)
* Serum amylase =< 1.5 x ULN (must be performed within 7 days prior to enrollment)
* Serum lipase =< 1.5 x ULN (must be performed within 7 days prior to enrollment)
* Grade 1 or lower calcium level

* Note: can have history of hypercalcemia as long as controlled and asymptomatic
Minimum age
12 Months
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies, OR because there is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in female patients of childbearing potential. Female patients of childbearing potential are defined as those who are past the onset of menarche and are not surgically sterile (i.e., bilateral salpingectomy, bilateral oophorectomy, complete hysterectomy) or post-menopausal. Males or females of reproductive potential may not participate unless they have agreed to use two effective methods of birth control, including a medically accepted barrier or contraceptive method (e.g., male or female condom) for the duration of therapy and at least 90 days after final dose of tiragolumab and 150 days after final dose of atezolizumab, whichever is later. Abstinence is an acceptable method of birth control.

* It is not known if atezolizumab or tiragolumab are present in breast milk; however, IgG immunoglobulins are found in milk. Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended during therapy and for at least 150 days after the last dose of atezolizumab and 90 days after the last dose of tiragolumab, whichever is later
* Concomitant medications:

* Corticosteroids:

* Patients must not be receiving concomitant systemic steroid medications and >= 14 days must have elapsed since last dose of systemic corticosteroid with the following exceptions:

* The use of physiologic doses of corticosteroids (5 mg/m^2/day up to 10 mg/day of prednisone equivalent) is acceptable
* The use of topical, inhaled, or ophthalmic corticosteroids are acceptable
* The use of acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g. 48 hours of corticosteroids for a contrast allergy) are acceptable
* Investigational drugs: Patients who are currently receiving another investigational drug are not eligible
* Anti-cancer Agents: Patients who are currently receiving other anti-cancer agents are not eligible
* Systemic immunosuppressive medications (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, and thalidomide) during study treatment because these agents could potentially alter the efficacy and safety of study treatments would not be eligible
* Patients must not have a known hypersensitivity to any component of tiragolumab or atezolizumab injection
* History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
* Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab or tiragolumab formulation
* Patients who have undergone allogeneic bone marrow or allogeneic cell transplant are not eligible
* Patients with CNS metastases from non-CNS primary tumors are not eligible unless CNS metastases have been previously treated and sequential imaging shows no evidence for active disease in the CNS.

* Patients with primary CNS tumors (including ATRT) with involvement of the brainstem are not eligible. Note: Patients with ATRT with M0-M4 disease without involvement of the brain stem are allowed to participate
* Patients must not have active autoimmune disease that has required systemic treatment in the past 12 months, or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy are not excluded. Replacement therapy (e.g. thyroxine, insulin, physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and these patients are eligible
* Patients who have active immune deficiency are not eligible
* Patients who have known active tuberculosis are not eligible
* Hepatitis B or C infection:
* Patients < 18 years old at enrollment, who have known hepatitis B or C
* Patients >= 18 years old at enrollment with:

* Positive hepatitis B surface antigen (HBsAg), OR
* Positive total hepatitis B core antibody (HBcAb) who have a quantitative hepatitis B virus (HBV) deoxyribonucleic acid (DNA) >= 500 IU/mL, OR
* Positive hepatitis C virus (HCV) antibody with a positive HCV ribonucleic acid (RNA) test
* Note: For adults (>= 18 years old at enrollment), hepatitis B serology testing is required to determine eligibility. The HBV DNA test is required only for patients who have a negative HBsAg test, a negative HBsAb test, and a positive total HBcAb test. For adults (>= 18 years old at enrollment), hepatitis C serology testing is required to determine eligibility. The HCV RNA test is required only for patients who have a positive HCV antibody test
* Patients who have a known, recent Epstein-Barr virus (EBV) infection or known history of chronic, active infection are not eligible
* Patients who have history of or active human immunodeficiency virus (HIV) are not eligible except patients who are stable on anti-retroviral therapy, have a CD4 count >= 200/uL, and have an undetectable viral load
* Patients who have significant cardiovascular disease (such as New York Heart Association class III or IV congestive heart failure, myocardial infarction, or cerebrovascular accident) within 3 months prior to study enrollment, unstable arrhythmia, or unstable angina are not eligible
* Patients who have a major surgical procedure, other than for diagnosis, within 4 weeks prior to study enrollment, or the anticipation of the need for a major surgical procedure during the study are not eligible
* Patients who have a history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or known active pneumonitis are not eligible. History of radiation pneumonitis in the radiation field is permitted
* Patients who have uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) are not eligible. Patients with indwelling catheters (e.g., PleurX) are allowed
* Patients who have an uncontrolled infection are not eligible
* Patients who have received a prior solid organ transplantation are not eligible
* Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
17/11/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/09/2025
Actual
Sample size
Target
86
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 0 0
Queensland Children's Hospital - South Brisbane
Recruitment postcode(s) [1] 0 0
4101 - South Brisbane
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
District of Columbia
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Indiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Maryland
Country [9] 0 0
United States of America
State/province [9] 0 0
Massachusetts
Country [10] 0 0
United States of America
State/province [10] 0 0
Michigan
Country [11] 0 0
United States of America
State/province [11] 0 0
Minnesota
Country [12] 0 0
United States of America
State/province [12] 0 0
Missouri
Country [13] 0 0
United States of America
State/province [13] 0 0
New York
Country [14] 0 0
United States of America
State/province [14] 0 0
North Carolina
Country [15] 0 0
United States of America
State/province [15] 0 0
Ohio
Country [16] 0 0
United States of America
State/province [16] 0 0
Oregon
Country [17] 0 0
United States of America
State/province [17] 0 0
Pennsylvania
Country [18] 0 0
United States of America
State/province [18] 0 0
Tennessee
Country [19] 0 0
United States of America
State/province [19] 0 0
Texas
Country [20] 0 0
United States of America
State/province [20] 0 0
Utah
Country [21] 0 0
United States of America
State/province [21] 0 0
Washington
Country [22] 0 0
United States of America
State/province [22] 0 0
Wisconsin
Country [23] 0 0
Canada
State/province [23] 0 0
Ontario
Country [24] 0 0
Canada
State/province [24] 0 0
Quebec

Funding & Sponsors
Primary sponsor type
Government body
Name
National Cancer Institute (NCI)
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Mary F Wedekind Malone
Address 0 0
Pediatric Early Phase Clinical Trial Network
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://grants.nih.gov/policy/sharing.htm


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05286801