Trial Title:
Testing the Combination of Anti-cancer Drugs Atezolizumab and Tiragolumab in People With Advanced Stage Rare Cancers, RARE3 Trial
NCT ID:
NCT05715281
Condition:
Advanced Rare Malignant Solid Neoplasm
Rare Malignant Solid Neoplasm
Refractory Rare Malignant Solid Neoplasm
Conditions: Official terms:
Neoplasms
Atezolizumab
Antibodies, Monoclonal
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Atezolizumab
Description:
Given IV
Arm group label:
Treatment (atezolizumab, tiragolumab)
Other name:
MPDL 3280A
Other name:
MPDL 328OA
Other name:
MPDL-3280A
Other name:
MPDL3280A
Other name:
MPDL328OA
Other name:
RG 7446
Other name:
RG-7446
Other name:
RG7446
Other name:
RO 5541267
Other name:
RO-5541267
Other name:
RO5541267
Other name:
Tecentriq
Intervention type:
Procedure
Intervention name:
Biopsy
Description:
Undergo tumor biopsy
Arm group label:
Treatment (atezolizumab, tiragolumab)
Other name:
BIOPSY_TYPE
Other name:
Bx
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Treatment (atezolizumab, tiragolumab)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT scan
Arm group label:
Treatment (atezolizumab, tiragolumab)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized axial tomography (procedure)
Other name:
Computerized Tomography
Other name:
Computerized Tomography (CT) scan
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Procedure
Intervention name:
Echocardiography
Description:
Undergo ECHO
Arm group label:
Treatment (atezolizumab, tiragolumab)
Other name:
EC
Intervention type:
Drug
Intervention name:
Tiragolumab
Description:
Given IV
Arm group label:
Treatment (atezolizumab, tiragolumab)
Summary:
This phase II trial tests how well atezolizumab works in combination with tiragolumab in
treating patients with rare solid tumors that may have spread from where they first
started to nearby tissue, lymph nodes, or distant parts of the body (advanced stage).
Immunotherapy with monoclonal antibodies, such as atezolizumab and tiragolumab, may help
the body's immune system attack the cancer, and may interfere with the ability of tumor
cells to grow and spread. The study biopsy takes small pieces of cancer tissue from a
tumor. The purpose of these biopsies is to compare the body's immune response against the
tumor before and after treatment with the study drugs. Blood samples will also be
collected for the study. The researchers will use the samples to learn more about how
atezolizumab and tiragolumab work and which patients in the future might be most likely
to respond to atezolizumab and tiragolumab. Using atezolizumab in combination with
tiragolumab may help to shrink tumors in patients diagnosed with advanced stage rare
solid-tumor cancers.
Detailed description:
PRIMARY OBJECTIVE:
I. Determine the proportion of activated CD8+ T cells at baseline and after treatment
with atezolizumab and tiragolumab.
SECONDARY OBJECTIVES:
I. Determine the objective response rate (ORR) of patients with advanced rare cancers to
the combination of atezolizumab and tiragolumab using Response Evaluation Criteria in
Solid Tumors (RECIST) version (v) 1.1 and Immune-Modified (i)RECIST guidelines.
II. Measure progression-free survival (PFS) time (time frame: baseline until disease
progression, death, loss to follow-up, initiation of another anti-cancer treatment,
withdrawal of consent, or study termination).
III. Measure the proportion of patients with a clinically promising increase in CD8+ T
cell infiltration following treatment with atezolizumab and tiragolumab.
EXPLORATORY OBJECTIVES:
I. Investigate immune activation markers and the immune composition (regulatory T [Treg],
natural killer [NK], B-cells, macrophages, myeloid-derived suppressor cells [MDSC], tumor
mutation burden [TMB], microsatellite instability [MSI]) in tumor microenvironment (TME)
before and after study treatment.
II. Measure T cell receptor (TCR) signaling in tumor-infiltrating T cells in the TME as
well as in circulating T cells in blood before and after study treatment using multiplex
immunofluorescence assays (IFAs)-developed by the National Cancer Institute
(NCI)-Frederick Pharmacodynamic Assay Development & Implementation Section (PADIS)-and
use these measurements to evaluate the relationship between TCR signaling in circulating
T cells and TME.
III. Evaluate potential associations between atezolizumab and tiragolumab activity and
tumor genomic alterations, genomic expression, or TMB as determined from genomic analysis
of biopsy samples.
IV. Evaluate genomic alterations in cell free deoxyribonucleic acid (DNA) (cfDNA) and
their potential association with therapy response or resistance.
V. Evaluate the pharmacodynamic effects of the treatment on biomarkers of cell death and
epithelial-to-mesenchymal transition (EMT) in tumor tissue and circulating tumor cells
(CTCs).
VI. Evaluate markers of immune response and the presence of tertiary lymphoid structures
(TLS) in TME at baseline and following atezolizumab plus tiragolumab therapy.
OUTLINE:
Patients receive atezolizumab intravenously (IV) over 60 minutes and tiragolumab IV over
30-90 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of
disease progression or unacceptable toxicity. Patients also undergo echocardiography
(ECHO) at baseline, undergo biopsy at baseline and on study, and undergo computed
tomography (CT) and collection of blood samples throughout the study.
After completion of study treatment, patients are followed up for 30 days.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Patients must have histologically confirmed rare solid tumors that have progressed
on standard therapy or for whom there is no standard of care therapy
- Patients must not be eligible for a higher priority study that would be
feasible for them to enroll in, such as a disease specific study of phase 2 or
higher or a randomized study. Specifically, patients who are eligible for the
PEP-CTN pediatric trial of atezolizumab and tiragolumab in children,
adolescents, and young adults with SMARCB1- or SMARCA4-deficient tumors should
be excluded
- Patients must have measurable disease as defined by RECIST v1.1, with at least one
lesion that can be accurately measured in at least one dimension (longest diameter
to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm
(>= 2 cm) by chest x-ray or as >= 10 mm (>= 1 cm) with CT scan, MRI, or calipers by
clinical exam)
- Patients must have a tumor site amenable to biopsy
- Age >= 18 years. Because biopsies are mandatory on this trial, patients < 18 years
of age are excluded
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
- Absolute neutrophil count >= 1,500/mcL
- Platelets >= 100,000/mcL
- International normalized ratio (INR) or activated partial thromboplastin time (aPTT)
=< 1.5x institutional upper limit of normal (ULN)
- Patients who receive therapeutic anticoagulation therapy should be on a stable
dose
- Total bilirubin =< 1.5 x institutional ULN (however, patients with known Gilbert
disease who have serum bilirubin level of up to 3 mg/dl may be enrolled)
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase [SGPT])
=< 2.5 x institutional ULN (AST and/or ALT =< 5 x ULN for patients with liver
involvement)
- Creatinine =< 1.5 x institutional ULN OR creatinine clearance levels >= 30
mL/min/1.73 m^2 are permitted as the study agents are not secreted by the kidney
- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
therapy with undetectable viral load within 6 months are eligible for this trial.
For these patients, an HIV viral load test must be completed within 28 days prior to
enrollment
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV
viral load must be undetectable on suppressive therapy, if indicated
- Patients with a history of hepatitis C virus (HCV) infection must have been treated
and cured. For patients with HCV infection who are currently on treatment, they are
eligible if they have an undetectable HCV viral load
- Patients with treated brain metastases are eligible if follow-up brain imaging after
central nervous system (CNS)-directed therapy shows no evidence of progression for
more than >= 1 month after treatment of the brain metastases
- Patients with new or progressive brain metastases (active brain metastases) or
leptomeningeal disease are eligible if the treating physician determines that
immediate CNS specific treatment is not required and is unlikely to be required
during the first cycle of therapy
- Patients with a prior or concurrent malignancy whose natural history or treatment
does not have the potential to interfere with the safety or efficacy assessment of
the investigational regimen are eligible for this trial
- Patients with known history or current symptoms of cardiac disease, or history of
treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac
function using the New York Heart Association Functional Classification. To be
eligible for this trial, patients should be class 2B or better
- Willingness to provide biopsy samples for research purposes
- Administration of atezolizumab and tiragolumab may have an adverse effect on
pregnancy and poses a risk to the human fetus, including embryo-lethality. Female
patients of child-bearing potential and male patients must agree to use adequate
contraception (hormonal or barrier method of birth control; abstinence) prior to
study entry, for the duration of study participation, and for 5 months (150 days)
after the last dose of study agent. Should a woman become pregnant or suspect she is
pregnant while she or her partner is participating in this study, she should inform
her treating physician immediately
- Ability to understand and the willingness to sign a written informed consent
document
Exclusion Criteria:
- Patients who have had prior monoclonal antibody therapy must have completed that
therapy >= 5 weeks (or 3 half-lives of the antibody, whichever is shorter) prior to
start of treatment (minimum of 1 week between prior therapy and study enrollment)
- Patients must have recovered from clinically-significant adverse events of their
most recent cancer immunotherapy to grade 1 or less, (with the exception of alopecia
and lymphopenia)
- Patients who are receiving any other investigational agents
- Prior anti-TIGIT therapy is not allowed. However, other prior immune checkpoint
inhibitor therapy is permitted
- History of severe allergic, anaphylactic, or other hypersensitivity reactions to
chimeric or humanized antibodies (i.e., antibodies with generic names ending in
"ximab" or "zumab", respectively) or fusion proteins, not resolved by pre-medication
or steroids, leading to subsequent treatment cessation. Patients with a history of
allergic reaction to chimeric or humanized antibodies for which symptoms never
recurred after subsequent re-challenge may be considered after careful medical
history review
- Treatment with systemic immunosuppressive medications (including, but not limited
to, prednisone [> 10 mg/day], cyclophosphamide, azathioprine, methotrexate,
thalidomide, and anti-tumor necrosis factor [anti-TNF] agents) within 2 weeks prior
to Cycle 1, Day 1
- Patients who have received acute, low dose, systemic immunosuppressant
medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled
- The use of inhaled corticosteroids and systemic mineralocorticoids (e.g.,
fludrocortisone) for patients with orthostatic hypotension or adrenocortical
insufficiency is allowed
- Patients with uncontrolled intercurrent illness, that would limit compliance with
study requirements
- Pregnant women are excluded from this study because atezolizumab and tiragolumab are
investigational agents with unknown potential for teratogenic or abortifacient
effects. Because there is an unknown but potential risk for adverse events in
nursing infants secondary to treatment of the mother with atezolizumab, and because
it is not known if tiragolumab can be excreted in human milk, breastfeeding should
be discontinued if the mother is treated with atezolizumab
- History or risk of autoimmune disease, including, but not limited to, systemic lupus
erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis
associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's
syndrome, Bell's palsy, Guillain-Barre syndrome, multiple sclerosis, autoimmune
thyroid disease, vasculitis, or glomerulonephritis
- Patients with a history of autoimmune hypothyroidism on a stable dose of
thyroid replacement hormone may be eligible
- Patients with autoimmune hyperthyroid disease not requiring immunosuppressive
treatment may be eligible
- Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen
may be eligible
- Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with
dermatologic manifestations only (e.g., patients with psoriatic arthritis would
be excluded) are permitted provided that they meet the following conditions
- Patients with psoriasis must have a baseline ophthalmologic exam to rule
out ocular manifestations
- Rash must cover less than 10% of body surface area (BSA)
- Disease is well controlled at baseline and only requiring low potency
topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%,
fluocinolone 0.01%, desonide 0.05%, alclometasone dipropionate 0.05%)
- No acute exacerbations of underlying condition within the last 12 months
(not requiring psoralen plus ultraviolet A radiation [PUVA], methotrexate,
retinoids, biologic agents, oral calcineurin inhibitors; high potency or
oral steroids)
- Patients with active tuberculosis (TB) are excluded
- Severe infections within 4 weeks prior to cycle 1, day 1, including, but not limited
to, hospitalization for complications of infection, bacteremia, or severe pneumonia
- Signs or symptoms of infection within 2 weeks prior to Cycle 1, Day 1
- Received oral or intravenous (IV) antibiotics within 2 weeks prior to Cycle 1, Day
1. Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary
tract infection or chronic obstructive pulmonary disease) are eligible
- Patients who have undergone major surgical procedures prior to Cycle 1, Day 1 who
have not recovered to ECOG performance status =< 2 (Karnofsky >= 60%)
- 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
and up to 5 months after the last dose of atezolizumab
- Influenza vaccination should be given during influenza season only
(approximately October to March). Patients must not receive live, attenuated
influenza vaccine within 4 weeks prior to Cycle 1, Day 1 or at any time during
the study
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
National Cancer Institute Developmental Therapeutics Clinic
Address:
City:
Bethesda
Zip:
20892
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
800-411-1222
Investigator:
Last name:
Jibran Ahmed
Email:
Principal Investigator
Facility:
Name:
National Institutes of Health Clinical Center
Address:
City:
Bethesda
Zip:
20892
Country:
United States
Status:
Active, not recruiting
Start date:
September 26, 2023
Completion date:
October 15, 2026
Lead sponsor:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
National Cancer Institute (NCI)
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05715281
