Trial Title:
Carboplatin, Pemetrexed, and Atezolizumab in Patients With Non-squamous Non-small Cell Lung Cancer (NSCLC) and Untreated Brain Metastases
NCT ID:
NCT05746481
Condition:
Non-small Cell Lung Cancer
Conditions: Official terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Neoplasm Metastasis
Brain Neoplasms
Carboplatin
Pemetrexed
Atezolizumab
Conditions: Keywords:
PD-L1 tumor proportion score (TPS)
salvage radiation therapy
brain metastases
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:
Drug
Intervention name:
Tiragolumab
Description:
Tiragolumab (an investigational novel immune checkpoint inhibitor): 600 mg IV for
induction treatment administered on Day 1 of each 21-day cycle for 4 cycles. Maintenance
therapy will continue with tiragolumab on Day 1 of each 21-day cycle.
Arm group label:
Single Treatment Arm
Other name:
RO7092284
Intervention type:
Drug
Intervention name:
Atezolizumab
Description:
Atezolizumab (monoclonal antibody): 1200 mg IV administered on Day 1 of each 21-day
cycle.
Arm group label:
Single Treatment Arm
Other name:
Tecentriq
Other name:
RO5541267
Intervention type:
Drug
Intervention name:
Pemetrexed
Description:
Pemetrexed (antifolate antineoplastic agent chemotherapy): 500 mg/m2 administered IV on
Day 1 of each 21-day cycle.
Arm group label:
Single Treatment Arm
Other name:
Alimta
Other name:
Pemfexy
Intervention type:
Drug
Intervention name:
Carboplatin
Description:
Carboplatin AUC 5 (alkylating agent chemotherapy): injection administered on Day 1 of
each 21-day cycle.
Arm group label:
Single Treatment Arm
Other name:
Paraplatin
Summary:
This clinical trial is aimed at the evaluation of the safety and clinical activity of
tiragolumab in combination with carboplatin, pemetrexed and atezolizumab in the first
line treatment of metastatic non-squamous NSCLC patients with asymptomatic untreated
brain metastases.
Detailed description:
This is a phase II clinical trial aimed at the evaluation of the safety and clinical
activity of tiragolumab in combination with carboplatin, pemetrexed and atezolizumab in
the first line treatment of metastatic non-squamous NSCLC patients with asymptomatic
untreated brain metastases. Patients with at least one untreated evaluable brain
metastasis of 5 mm or more will be enrolled. Lesions previously treated with SRS may not
be used as target lesions. Patients will be required to undergo an on-treatment brain MRI
at three weeks for safety purposes. Additional restaging will occur at nine-week
intervals. PD-L1 tumor proportion score (TPS) will be determined utilizing an
FDA-approved test by local testing.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Patients must have histologically or cytologically confirmed non-squamous NSCLC.
- Patients must have asymptomatic brain metastases with at least one untreated
evaluable (per RANO-BM) brain metastasis of 5 mm or more. A growing lesion
previously treated with whole brain radiotherapy is acceptable given the lower
incidence of radiation necrosis. Lesions previously treated with SRS may not be used
as target lesions.
o Patients are not required to have measurable disease outside the CNS per RECIST
1.1.
- Prior chemotherapy, immunotherapy or radiation given with curative intent in early
stage or locoregionally advanced NSCLC is permitted, if completed more than 12
months prior to initiation of study treatment.
- Prior radiation with palliative intent in the metastatic setting to non-CNS lesions
is permitted (no wash-out period).
- Age ≥18 years.
- ECOG performance status ≤ 1.
- Life expectancy ≥12 weeks.
- Patients must have normal organ and marrow function as defined below:
- Absolute neutrophil count ≥1,500/mcL
- Platelets ≥100,000/mcL
- Total bilirubin ≤ institutional upper limit of normal (ULN)
- AST(SGOT)/ALT(SGPT) ≤2.5 × institutional ULN
- Creatinine Clearance (CrCl) ≥45 mL/min/1.73 m2
- No known history of HIV, with the following exception: patients who are HIV positive
are eligible provided they are stable on anti-retroviral therapy, have a CD4 count ≥
200/µL, and have an undetectable viral load.
- Negative hepatitis B surface antigen (HBsAg) test at screening. If positive, an HBV
DNA test must also be performed to determine if the patient has an HBV infection,
which would render the patient ineligible. Patients receiving treatment with
anti-viral therapy for HBV are excluded.
- Negative hepatitis C antibody. If positive, an HCV RNA test must also be performed
to determine if the patient has an HCV infection, which would render the patient
ineligible.
- Availability of a representative tumor specimen for exploratory biomarker research.
- For women of childbearing potential: agreement to remain abstinent (refrain from
heterosexual intercourse) or use contraception:
- Women must remain abstinent or use contraceptive methods with a failure rate of < 1%
per year during the treatment period and for 90 days after the final dose of
tiragolumab, 5 months after the final dose of atezolizumab, and 6 months after the
final dose of paclitaxel, pemetrexed, gemcitabine, carboplatin, or cisplatin.
- A woman is considered to be of childbearing potential if she is postmenarchal,
has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea
with no identified cause other than menopause), and has not undergone surgical
sterilization (i.e., removal of ovaries, fallopian tubes, and/or uterus) or
another cause as determined by the investigator (e.g., Müllerian agenesis). Per
this definition, a woman with a tubal ligation is considered to be of
childbearing potential. The definition of childbearing potential may be adapted
for alignment with local guidelines or regulations.
- 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 adequate methods of
contraception. If required per local guidelines or regulations, locally
recognized adequate methods of contraception and information about the
reliability of abstinence will be described in the local Informed Consent Form.
- Women who would like to become pregnant after study treatment discontinuation should
seek advice on oocyte cryopreservation prior to initiation of study treatment
because of the possibility of irreversible infertility due to treatment with
cisplatin and carboplatin.
- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or
use a condom, and agreement to refrain from donating sperm, as defined below:
- With a female partner of childbearing potential, men who are not surgically
sterile must remain abstinent or use a condom plus an additional contraceptive
method that together result in a failure rate of < 1% per year during the
treatment period, for 90 days after the final dose of tiragolumab, and for 6
months after the final dose of paclitaxel, pemetrexed, gemcitabine, carboplatin
or cisplatin. Men must refrain from donating sperm during this same period.
- With a pregnant female partner, men must remain abstinent or use a condom
during the treatment period for 90 days after the final dose of tiragolumab,
and for 6 months after the final dose of paclitaxel, pemetrexed, gemcitabine,
carboplatin, or cisplatin to avoid exposing the embryo.
- 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 adequate methods of
contraception. If required per local guidelines or regulations, locally
recognized adequate methods of contraception and information about the
reliability of abstinence will be described in the local Informed Consent Form.
- Men who would like to father a child after study treatment initiation should be
advised regarding the conservation of sperm prior to treatment because of the
possibility of irreversible infertility resulting from chemotherapies used in this
study.
- Women of childbearing potential must have a negative serum pregnancy test result
within 14 days prior to initiation of study treatment.
- Ability to understand and the willingness to sign a written informed consent
document.
Exclusion Criteria:
- Symptoms related to brain metastases requiring CNS radiation ≤ 2 weeks of treatment
initiation are exclusionary. Steroids greater than prednisone 10 mg/d or equivalent,
or anti-epileptic therapy ≤ 2 weeks of treatment initiation are exclusionary.
- Prior systemic therapy for metastatic disease is not allowed.
- Patients whose tumors harbor oncogenic drivers with an approved 1st line therapy
(e.g. EGFR, ALK, and ROS1 alterations) are excluded.
- Patients who are receiving any other investigational agents.
- 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 syndrome, Guillain-Barré
syndrome, or multiple sclerosis, with the following exceptions:
- 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 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.
- 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 or fibrosis in a radiation field is permitted.
- History of leptomeningeal disease.
- Active tuberculosis.
- Significant cardiovascular disease (such as New York Heart Association Class II or
greater cardiac disease, myocardial infarction, or cerebrovascular accident) within
3 months prior to initiation of study treatment, unstable arrhythmia, or unstable
angina.
- 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 study.
- History of malignancy other than NSCLC within 2 years prior to screening, with the
exception of malignancies with a negligible risk of metastasis or death (e.g.,
5-year OS rate ≥ 90%).
- Severe infection within 2 weeks prior to initiation of study treatment, including,
but not limited to, hospitalization for complications of infection, bacteremia, or
severe pneumonia.
- Prior allogeneic stem cell or solid organ transplantation.
- 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.
- Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of
study treatment, or anticipation of need for such a vaccine during atezolizumab
treatment or within 5 months after the final dose of atezolizumab.
- Treatment with systemic immunosuppressive medication (including, but not limited to,
corticosteroids in excess of prednisone 10 mg/d or equivalent, 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 study treatment, with the following exceptions:
- Patients who received 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 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
- History of allergic reactions attributed to compounds of similar chemical or
biologic composition to atezolizumab or other agents used in study.
- 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.
- Pregnancy or breastfeeding, or intention of becoming pregnant during study
treatment, within 90 days after the final dose of tiragolumab, 5 months after the
final dose of atezolizumab, or 6 months after the final dose of pemetrexed,
gemcitabine, paclitaxel, carboplatin, or cisplatin o Women of childbearing potential
must have a negative serum pregnancy test result within 14 days prior to initiation
of study treatment.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
UPMC Hillman Cancer Center
Address:
City:
Pittsburgh
Zip:
15232
Country:
United States
Status:
Recruiting
Contact:
Last name:
Jennifer Ruth, RN
Phone:
412-623-8963
Email:
ruthj2@upmc.edu
Investigator:
Last name:
Liza Villaruz, MD
Email:
Principal Investigator
Start date:
August 8, 2023
Completion date:
April 30, 2027
Lead sponsor:
Agency:
Liza Villaruz, MD
Agency class:
Other
Collaborator:
Agency:
Genentech, Inc.
Agency class:
Industry
Source:
University of Pittsburgh
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05746481
