Trial Title:
Phase I/II Trial in ES-SCLC to Enhance Response to Atezolizumab Plus Chemotherapy With Total Body Irradiation
NCT ID:
NCT06110572
Condition:
Extensive Stage Lung Small Cell Carcinoma
Stage IV Lung Cancer
Conditions: Official terms:
Carcinoma, Small Cell
Small Cell Lung Carcinoma
Carboplatin
Etoposide
Atezolizumab
Study type:
Interventional
Study phase:
Phase 1/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:
Carboplatin
Description:
Given by IV
Arm group label:
Treatment (carboplatin, atezolizumab, etoposide, TBI, H-RT)
Intervention type:
Biological
Intervention name:
Atezolizumab
Description:
Given by IV
Arm group label:
Treatment (carboplatin, atezolizumab, etoposide, TBI, H-RT)
Intervention type:
Drug
Intervention name:
Etoposide
Description:
Given by IV
Arm group label:
Treatment (carboplatin, atezolizumab, etoposide, TBI, H-RT)
Intervention type:
Radiation
Intervention name:
Total Body Irradiation
Description:
Undergo Total Body Irradiation
Arm group label:
Treatment (carboplatin, atezolizumab, etoposide, TBI, H-RT)
Intervention type:
Radiation
Intervention name:
Hypofractionated Radiation Therapy
Description:
Undergo Hypofractionated Radiation Therapy
Arm group label:
Treatment (carboplatin, atezolizumab, etoposide, TBI, H-RT)
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo Magnetic Resonance Imaging
Arm group label:
Treatment (carboplatin, atezolizumab, etoposide, TBI, H-RT)
Summary:
This phase I/II trial studies the side effects, safety, and effectiveness of low dose
radiation to the entire body (total body irradiation [TBI]) and higher dose radiation to
known areas of cancer (hypofractionated radiation therapy [H-RT]) combined with
atezolizumab and chemotherapy (carboplatin & etoposide) in treating patients with small
cell lung cancer that has spread to disease sites outside of the lung (extensive stage).
Extensive stage disease has historically been treated with chemotherapy alone with
consideration of chest (thoracic) radiation therapy for those with response to
chemotherapy, as well as consideration of preventative radiation therapy to the head
(prophylactic cranial irradiation). Emerging evidence supports the synergistic
interactions between immunotherapy and radiation therapy. Immunotherapy with monoclonal
antibodies, such as atezolizumab, may help the body's immune system attack the cancer,
and may interfere with the ability of tumor cells to grow and spread. Carboplatin is in a
class of medications known as platinum-containing compounds. It works in a way similar to
the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin
works by killing, stopping or slowing the growth of tumor cells. Etoposide is in a class
of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed
for cell division and DNA repair and may kill tumor cells. Combining TBI and H-RT with
atezolizumab and chemotherapy may improve response to treatment.
Detailed description:
PRIMARY OBJECTIVES:
I. Evaluate the safety of the addition of total body irradiation (TBI) and
hypo-fractionated radiation (H-RT) to atezolizumab and chemotherapy in patients with
extensive stage-small cell lung carcinoma (ES-SCLC).
II. Evaluate the efficacy of the addition of TBI and H-RT to atezolizumab and
chemotherapy in patients with ES-SCLC.
SECONDARY OBJECTIVE:
I. Evaluate the progression free survival benefit and local and systemic control benefits
of the addition of TBI and H-RT to atezolizumab and chemotherapy in patients with
ES-SCLC.
OUTLINE:
INDUCTION PHASE: Patients receive carboplatin intravenously (IV) and atezolizumab IV on
day 1 of each cycle and etoposide IV on days 1-3 of each cycle. Treatment repeats every
21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
Patients also receive TBI twice daily (BID) on day 18 or 19 of cycle 1 and beginning 2-3
days later, H-RT daily over 7 days in the absence of disease progression or unacceptable
toxicity.
MAINTENANCE PHASE: Patients receive atezolizumab IV on day 1 of each cycle. Treatment
repeats every 21 days for 12 cycles in the absence of disease progression or unacceptable
toxicity.
Patients also undergo computed tomography (CT) and magnetic resonance imaging (MRI)
throughout the trial.
After completion of study treatment, patients are followed up within 30 days and then
every 3-4 months for up to 3 years.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Age ≥ 18 years at time of informed consent
- Histologically documented or cytologically confirmed diagnosis of extensive stage
small-celllung cancer with evaluable disease per RECIST v1.1 criteria. Patients may
be considered extensive-stage based on M1 disease per AJCC 8th edition, OR may be
clinically staged as extensive-stage disease based on anatomical extent that would
preclude the use of standard radiotherapy fields as assessed by the treating
radiation oncologist.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
- Platelet count ≥ 100 x 10^9/L
- Lymphocyte count ≥ 0.5 x 10^9/L
- Hemoglobin ≥ 9 g/dL
- Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
- Aspartate aminotransferase (AST) ≤ 2.5 x ULN, alanine aminotransferase (ALT) ≤ 2.5 x
ULN and alkaline phosphatase ≤ 2.5 x ULN
- Creatinine ≤ 1.5 x ULN or calculated creatinine clearance (CrCl) ≥ 50 mL/min if
creatinine (Cr) > 1.5 x ULN. GFR can also be utilized. If no local calculation
guidance on CrCl, should be calculated according to Cockcroft-Gault Method
- International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 x ULN and
activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless participant is
receiving anticoagulation therapy. For patients receiving therapeutic
anticoagulation: stable anticoagulant regimen.
- Negative HIV test at screening, with the following exception: patients with positive
HIV test at screening are eligible provided they are stable on anti-retroviral
therapy, have a CD4 count ≥ 200, and have an undetectable viral load
- Negative Hepatitis B surface antigen at screening
- Presence of brain metastases allowed (should undergo management with surgery and/or
radiation therapy if symptomatic prior to TESSERACT radiation regimen; upfront
cranial irradiation not mandatory on protocol if asymptomatic)
- Contraceptive use should be initiated or continued per guidance in labeling for
approved chemotherapies
- Female patients must be non-pregnant and not breastfeeding
- Women of childbearing potential (WOCBP) must remain abstinent or use contraceptive
methods with a failure rate of <1% per year during the treatment period and for 5
months after the final dose of atezolizumab. A woman is considered to be of
childbearing potential if she is post-menarchal, has not reached a post-menopausal
state (12 months of amenorrhea with no identified cause other than menopause), and
has not undergone surgical sterilization (removal of ovaries and/or uterus). The
definition of childbearing potential may be adapted for alignment with local
guidelines or requirements.
- 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, symptomthermal or
postovulation methods) and withdrawal are not adequate methods of
contraception.
- With a female partner of childbearing potential who is not pregnant, 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 and for 5 months after the final dose of
atezolizumab. 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 and for 5 months after the final dose of
atezolizumab 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.
- Eligible for immunotherapy-based systemic regimens per judgment of patient's study
physician
- Able to submit written informed consent
Exclusion Criteria:
- Major surgery (requiring general anesthesia or at discretion of study physician)
within 4 weeks prior to study enrollment that would prevent treatment with TESSERACT
regimen
- Known clinically significant (per study physician) acute or chronic infections
including HIV (per inclusion criteria above), hepatitis B virus (HBV), hepatitis C
virus (HCV) or active tuberculosis (testing not required for tuberculosis [TB]).
Patients with HCV must be on stable dose of antiviral therapy on study entry.
Current treatment with antivirals for HBV is not allowed on study
- 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
- Uncontrolled hypertension (average systolic blood pressure greater than or equal to
140 or average diastolic blood pressure greater than or equal to 90 despite optimal
medical therapy). Patients with hypertension (systolic blood pressure [SBP] ≥ 140
and/or diastolic blood pressure [DBP] ≥ 90) may enroll provided that an effective
anti- hypertensive regimen is initiated.
- History of prior malignancy within 3 years of enrollment, except for adequately
treated basal or squamous cell carcinoma of the skin, adequately treated carcinoma
in situ (e.g. cervix or non- invasive bladder cancer) or other malignancy with
minimal risk of metastasis or death (survival > 90% at 5 years)
- Receipt of prior courses of cytotoxic chemotherapy or anti-neoplastic
biologic/immunotherapy for current malignancy (other than the current course of
therapy). Patients may have undergone 1 cycle of 1st line of systemic therapy for
SCLC prior to enrollment as long as the systemic therapy is congruent with what is
included in the protocol and part of the current course of therapy.
- Prior radiotherapy that would preclude delivery of protocol- based radiotherapy to
normal organ tolerance per patient's study physician
- Receipt of live attenuated vaccine within 28 days of cycle 1, day 1 (C1D1), and for
5 months after the last dose of atezolizumab.
- Use of prohibited concomitant drug
- Concurrent enrollment in another clinical trial (unless observational or within
follow-up period)
- Known, pathologically confirmed malignant pleural effusions (diagnostic evaluation
of pleural effusions are recommended but not required for study entry, especially if
sampling is deemed technically challenging at discretion of treating physician)
- Uncontrolled pleural or pericardial effusion or ascites requiring recurrent drainage
procedures (once monthly or more frequently). Patients with indwelling catheters
(e.g., PleurX) are allowed
- History of leptomeningeal disease
- Uncontrolled tumor-related pain: Patients requiring pain medication must be on a
stable regimen at study entry. Symptomatic lesions (e.g., bone metastases or
metastases causing nerve impingement) amenable to palliative radiotherapy can
undergo treatment with palliative radiotherapy prior to enrollment at discretion of
treating physicians. Patients should be recovered from effects of radiation and
there is no required minimum recovery period. Asymptomatic metastatic lesions that
would likely cause functional deficits or intractable pain with further growth
(e.g., epidural metastasis that is not currently associated with spinal cord
compression) can be considered for loco-regional therapy at discretion of treating
physician prior to enrollment.
- Uncontrolled or symptomatic hypercalcemia (ionized calcium > 1.5 mmol/L, calcium >
12 mg/dL or corrected serum calcium > ULN)
- 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, Sjogren syndrome, Guillain-Barre
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 the following conditions are
met:
- Rash must cover < 10% of body surface area
- Disease is well controlled at baseline and requires only low-potency
topical steroids
- 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 CT scan
- 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
- 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.
- Prior allogeneic stem cell or solid organ transplantation
- Any other disease, metabolic dysfunction, physical examination 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 investigational therapy within 28 days prior to initiation of study
treatment
- Prior treatment with CD137 agonists or immune checkpoint blockade therapies,
including anti- CTLA-4, and anti-PD-L1 therapeutic antibodies
- Treatment with systemic immunostimulatory agents including, but not limited to,
interferon and interleukin 2 (IL-2) within 4 weeks or 5 half-lives of the drug
(whichever is longer) prior to initiation of study treatment
- Treatment with systemic immunosuppressive medication including, but not limited to,
corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and
anti-TNF-alpha agents, within 2 weeks prior to initiation of study treatment with
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 after
Principal Investigator confirmation has been confirmed)
- Patients who are receiving mineral corticoids (e.g., fludrocortisone),
corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or
low-dose corticosteroids for orthostatic hypotension or adrenal sufficiency are
eligible for the study.
- Systemic steroids required during therapy for adverse event (AE) management are
allowed.
- 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 formulation
- Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment
or within 5 months of the last dose of Atezolizumab. 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:
Vanderbilt University/Ingram Cancer Center
Address:
City:
Nashville
Zip:
37232
Country:
United States
Status:
Recruiting
Contact:
Last name:
Vanderbilt-Ingram Service for Timely Access
Phone:
800-811-8480
Email:
cip@vumc.org
Investigator:
Last name:
Evan Osmundson, MD, PhD
Email:
Principal Investigator
Start date:
April 24, 2024
Completion date:
June 30, 2028
Lead sponsor:
Agency:
Vanderbilt-Ingram Cancer Center
Agency class:
Other
Collaborator:
Agency:
Genentech, Inc.
Agency class:
Industry
Source:
Vanderbilt-Ingram Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06110572
