Description:
This phase II trial studies the effect of lamivudine in combination with standard of care
chemoimmunotherapy in treating patients with extensive stage small cell lung cancer. Even
though small cell lung cancer is initially highly responsive to first-line chemotherapy
treatment, treatment resistance inevitably emerges; treatment resistance is when tumor cells
stop responding to a drug treatment that they had previously responded to. Lamivudine is an
oral antiviral a drug that may be able to reduce the ability of tumors to develop drug
resistance. Chemotherapy drugs, such as carboplatin and etoposide, work in different ways to
stop the growth of tumor cells, either by killing the cells, by stopping them from dividing,
or by stopping them from spreading. 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. Giving lamivudine together with the usual standard
of care chemoimmunotherapy may help prevent the growth and spread of the tumor cells to other
parts of the body.
Title
- Brief Title: Lamivudine in Combination With Chemoimmunotherapy for the Treatment of Extensive Stage Small Cell Lung Cancer
- Official Title: A Phase II Trial of Lamivudine in Combination With Chemoimmunotherapy in Patients With Extensive Stage SCLC
Clinical Trial IDs
- ORG STUDY ID:
I 691720
- SECONDARY ID:
NCI-2020-13169
- SECONDARY ID:
I 691720
- NCT ID:
NCT04696575
Conditions
- Extensive Stage Lung Small Cell Carcinoma
Interventions
Drug | Synonyms | Arms |
---|
Atezolizumab | MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG7446, RO5541267, Tecentriq | Treatment (lamivudine, chemoimmunotherapy) |
Carboplatin | Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo | Treatment (lamivudine, chemoimmunotherapy) |
Etoposide | Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16, VP 16-213, VP-16, VP-16-213, VP16 | Treatment (lamivudine, chemoimmunotherapy) |
Lamivudine | (-)-BCH-189, 3TC, Epivir, GR109714X, LAM | Treatment (lamivudine, chemoimmunotherapy) |
Purpose
This phase II trial studies the effect of lamivudine in combination with standard of care
chemoimmunotherapy in treating patients with extensive stage small cell lung cancer. Even
though small cell lung cancer is initially highly responsive to first-line chemotherapy
treatment, treatment resistance inevitably emerges; treatment resistance is when tumor cells
stop responding to a drug treatment that they had previously responded to. Lamivudine is an
oral antiviral a drug that may be able to reduce the ability of tumors to develop drug
resistance. Chemotherapy drugs, such as carboplatin and etoposide, work in different ways to
stop the growth of tumor cells, either by killing the cells, by stopping them from dividing,
or by stopping them from spreading. 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. Giving lamivudine together with the usual standard
of care chemoimmunotherapy may help prevent the growth and spread of the tumor cells to other
parts of the body.
Detailed Description
PRIMARY OBJECTIVE:
I. To evaluate the 6-month progression-free survival (PFS) rate of lamivudine in combination
with platinum-based chemotherapy in patients with extensive stage small cell lung cancer
(SCLC).
SECONDARY OBJECTIVES:
I. To evaluate the 12-month survival and overall survival (OS) of patients with extensive
stage SCLC receiving study treatment.
II. To assess the toxicity of the combination of lamivudine with platinum-based chemotherapy
in this population.
EXPLORATORY OBJECTIVE:
I. To study tissue and blood-based biomarkers as potential predictors of treatment efficacy.
OUTLINE:
INDUCTION: Patients receive lamivudine orally (PO) once daily (QD) on days 1-28. Patients
also receive carboplatin intravenously (IV) over 30-60 minutes and atezolizumab IV on day 1,
and etoposide IV over 60-120 minutes on days 1-3. Treatment repeats every 28 days for up to 4
cycles in the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Patients receive lamivudine PO QD on days 1-28 and atezolizumab IV on day 1.
Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
NOTE: Patients who are not eligible for atezolizumab as outlined in exclusion criteria or who
refuse to receive atezolizumab may still be treated in this study with carboplatin and
etoposide as the IV drug component, in addition to lamivudine orally administered.
After completion of study treatment, patients are followed up for 30 days and then every 60
days thereafter.
Trial Arms
Name | Type | Description | Interventions |
---|
Treatment (lamivudine, chemoimmunotherapy) | Experimental | INDUCTION: Patients receive lamivudine PO QD on days 1-28. Patients also receive carboplatin IV over 30-60 minutes and atezolizumab IV on day 1, and etoposide IV over 60-120 minutes on days 1-3. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Patients receive lamivudine PO QD on days 1-28 and atezolizumab IV on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
NOTE: Patients who are not eligible for atezolizumab as outlined in exclusion criteria or who refuse to receive atezolizumab may still be treated in this study with carboplatin and etoposide as the IV drug component, in addition to lamivudine orally administered. | - Atezolizumab
- Carboplatin
- Etoposide
- Lamivudine
|
Eligibility Criteria
Inclusion Criteria:
- Age >= 18 years of age
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of =< 1 at the
time of study treatment initiation
- Histologically or cytologically confirmed diagnosis of small cell lung cancer (SCLC)
- Patient should have extensive stage disease, defined as, malignant pleural effusion,
pulmonary metastases in a different lobe in the ipsilateral lung or contralateral
lung, and/or the presence of extra-thoracic metastatic disease
- Must have measurable disease based on Response Evaluation Criteria in Solid Tumors
(RECIST) 1.1 prior to starting platinum-based systemic chemotherapy
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
- Platelets >= 100 x 10^9/L
- Hemoglobin >= 9 g/dL
- Serum creatinine =< 1.5 x institution upper limit of normal (ULN) and calculated
creatinine clearance of at least 15 ml/min
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x upper limit
of normal (ULN) (ALT and AST =< 5 x ULN is acceptable if liver metastases are present)
- Total serum bilirubin =< 1.5 x ULN. For patients with well documented Gilbert's
syndrome, total bilirubin =< 3 x ULN with direct bilirubin within normal range
- Newly diagnosed SCLC patients may receive no more than 1 cycle of standard
chemotherapy or chemoimmunotherapy for their current diagnosis prior to study
treatment
- Patients who have progressed on prior treatment for SCLC will be eligible if both of
the following conditions are met:
- Received no more than one-line of treatment with platinum-based chemotherapy for
SCLC, and
- Last platinum-based treatment administered >= 12 months prior to diagnosis of
recurrence/relapse. Patients should not have experienced disease progression
while receiving prior platinum-based treatment for SCLC
- Participants of child-bearing potential must agree to use adequate contraceptive
methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study
entry. 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
- Participant or legal representative must understand the investigational nature of this
study and sign an approved written informed consent form prior to receiving any study
related procedure
Exclusion Criteria:
- Receipt of anticancer chemotherapy/chemoimmunotherapy within 4 weeks prior to the
first administration of study drug other than what is allowed in the inclusion
criteria
- Symptomatic brain metastasis
- Patients with treated brain metastases are eligible provided they have recovered
from effects of radiation and neurological symptoms are improved or controlled
for at least two weeks prior to enrollment
- Patients with asymptomatic brain metastases who are being treated with systemic
chemotherapy alone are also eligible if no more than 6 lesions each less than 1
cm in size is present at the time of initiating protocol treatment
- Leptomeningeal involvement regardless of treatment status
- Participation in another interventional study within the last 28 days of study
enrollment
- Had major surgery within 14 days prior to starting study drug or has not recovered
from major side effects (tumor biopsy is not considered major surgery) resulting from
a prior surgery
- Positive for immunosuppressive disease, acquired immunodeficiency syndrome (AIDS) or
other immune depressing diseases. For human immunodeficiency virus (HIV), HVC and
HBC-mandatory testing is required prior to enrollment
- Note: Patients with past or resolved hepatitis B virus (HBV) infection (defined
as the presence of hepatitis B surface antibody [HBsAb] and absence of hepatitis
B surface antigen [HBsAg]) are eligible (HBV deoxyribonucleic acid [DNA] should
be obtained in patients if only anti-hepatitis B core [HBc] antibody was present
prior to randomization). Patients with active/untreated hepatitis C virus (HCV)
will be excluded from the study; patients who test positive for HCV antibody are
eligible only if polymerase chain reaction (PCR) is negative for HCV ribonucleic
acid (RNA)
- Active, clinically serious infections or other serious uncontrolled medical
conditions, including chronic viral hepatitis (testing for hepatitis B, C required)
- Patient has known hypersensitivity to the components of the study drugs or any analogs
- History or current evidence of any condition, therapy, or laboratory abnormality that
might confound the results of the study, interfere with the patient's participation
for the full duration of the study, or is not in the best interest of the patient to
participate, in the opinion of the treating Investigator, including, but not limited
to:
- Myocardial infarction or arterial or venous thromboembolic events within 6 months
prior to baseline or severe or unstable angina, New York Heart Association (NYHA)
class III or IV disease
- History of documented congestive heart failure (New York Heart Association
functional classification III or IV) within 6 months prior to baseline
- Poorly controlled arrhythmias
- Contraindications to atezolizumab: Patients with active autoimmune disorder or prior
history of autoimmune disorder requiring immunosuppressive agents within preceding two
years will not be allowed to receive atezolizumab but will be able to receive the
other drugs included in the treatment regimen, if eligible
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Progression-free survival |
Time Frame: | From the date of registration to the date of first confirmed progression or death, whichever occurred first, assessed at 6 months |
Safety Issue: | |
Description: | The primary test of efficacy will be carried out using an exact binomial test of a proportion. Descriptive analyses will be carried out using the Kaplan-Meier product-limit estimator. Patients who are treated beyond RECIST progression and subsequently had tumor response while on study (and no other intervening treatment) will be classified as pseudoprogression and not counted as progression event. |
Secondary Outcome Measures
Measure: | Overall survival |
Time Frame: | From registration to death from any cause or 5 years from time of enrollment, whichever occurs first |
Safety Issue: | |
Description: | Descriptive analyses will be carried out using the Kaplan-Meier product-limit estimator. |
Measure: | Incidence of toxicities |
Time Frame: | Up to 30 days after the end of all treatment |
Safety Issue: | |
Description: | Per National Cancer Institute Common Terminology Criteria for Adverse Events version 5, the term toxicity is defined as adverse events that are classified as either possibly, probably, or definitely related to study treatment. The maximum grade for each type of toxicity will be recorded for each patient and will be used for reporting. Frequency tables will be reviewed to determine toxicity patterns. In addition, all adverse event data graded as 3, 4, or 5 and classified as either "unrelated or unlikely to be related" to study treatment in the event of an actual relationship developing will be reviewed. |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Roswell Park Cancer Institute |
Last Updated
July 7, 2021