Randomized Phase II/III Trial of Consolidation Radiation + Immunotherapy for ES-SCLC: RAPTOR Trial

  • STATUS
    Recruiting
  • End date
    Apr 30, 2027
  • participants needed
    138
  • sponsor
    National Cancer Institute (NCI)
Updated on 27 October 2022
ct scan
renal function
cancer
hysterectomy
prophylactic cranial irradiation
monoclonal antibodies
measurable disease
oophorectomy
pleural effusion
maintenance therapy
x-rays
etoposide
metastasis
neutrophil count
tumor cells
brain metastases
luteinizing hormone
atezolizumab

Summary

This phase II/III trial compares the effect of adding radiation therapy to the usual maintenance therapy with atezolizumab versus atezolizumab alone in patients who have already received atezolizumab plus chemotherapy for the treatment of small cell lung cancer that has spread outside of the lung or to other parts of the body (extensive stage). 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. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving radiation therapy in addition to atezolizumab may extend the time without extensive small cell lung cancer growing or spreading compared to atezolizumab alone.

Description

PRIMARY OBJECTIVES:

I. To compare investigator-assessed progression free survival (PFS) between atezolizumab plus radiotherapy and atezolizumab alone. (Phase II) II. To compare overall survival (OS) between atezolizumab plus radiotherapy and atezolizumab alone. (Phase III)

SECONDARY OBJECTIVES:

I. To assess the toxicity between the atezolizumab plus radiotherapy arm and the atezolizumab arm.

II. To assess the impact of adding radiotherapy on PFS and OS in patients with 1-3 visible tumors and > 3 visible tumors.

III. To assess the impact of adding radiotherapy on PFS and OS in patients receiving consolidation radiotherapy to all visible disease ("complete consolidation") and patients who do not receive consolidation radiation to all visible disease ("incomplete consolidation").

EXPLORATORY OBJECTIVE:

I. To assess the association between pre-treatment tumor burden (determined by central radiographic assessment, using both tumor number and tumor volume), and PFS and OS benefit.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive atezolizumab intravenously (IV) over 60 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive atezolizumab IV over 60 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo radiation therapy once daily (QD) on days 1-5 during weeks 1-5 only.

After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Details
Condition Extensive Stage Lung Small Cell Carcinoma
Treatment radiation therapy, Atezolizumab
Clinical Study IdentifierNCT04402788
SponsorNational Cancer Institute (NCI)
Last Modified on27 October 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Pathologically proven diagnosis of extensive stage small cell lung cancer
Partial response (PR) or stable disease (SD) after 4-6 cycles of etoposide/platinum (E/P) doublet plus atezolizumab by re-staging scans (positron emission tomography [PET]/computed tomography [CT] scan, diagnostic CT scan, magnetic resonance imaging [MRI] optional per treating physician); atezolizumab should continue through randomization. Patients must be randomized within 9 weeks of last dose of etoposide/platinum or 6 weeks from completion of prophylactic cranial irradiation (PCI)
At the time of enrollment, patients must have had measurable disease (per Response Evaluation Criteria in Solid Tumors [RECIST]) and 3 or fewer observable liver metastases and no evidence of progressive disease (per RECIST) at time of enrollment
Patients presenting with a pleural effusion will be eligible if thoracentesis is cytologically negative and non-bloody or if pleural fluid is too small a volume to effectively sample by thoracentesis and does not show increased metabolic activity on CT/PET imaging
Appropriate stage for study entry based on the following diagnostic workup
History/physical examination within 14 days prior to registration
Imaging within 42 days prior to registration to include
MRI brain with contrast or CT brain with contrast
CT chest, abdomen and pelvis or whole body PET/CT scan any time after the fourth cycle of chemotherapy and prior to registration
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 within 14 days
prior to registration
Absolute neutrophil count (ANC) >= 1,000/cells/mm^3 (within 14 days prior to registration)
Platelets >= 75,000 cells/mm^3 (within 14 days prior to registration)
Hemoglobin >= 8 g/dL (within 14 days prior to registration)
Total bilirubin =< 1.5 x upper limit of normal (ULN) (within 14 days prior to registration)
Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3.0 x ULN (AST and/or ALT =< 5 ULN for patients with liver involvement) (within 14 days prior to registration)
Alkaline phosphatase =< 2.5 x ULN (=< 5 ULN for patients with documented liver involvement or bone metastases) (within 14 days prior to registration)
Serum creatinine =< 2.0 x ULN (within 14 days prior to registration)
Adequate renal function within 30 days prior to registration defined as follows: glomerular filtration rate (GFR) >= 40 mL/min/1.73 m^2
Upfront radiation therapy of symptomatic metastatic site (excluded brain metastases) is permissible if causing patient pain or impending fracture
Patients with bone metastases are eligible. However, to assess response after radiation for bone metastases, must order at least diagnostic CT scan to measure response
For women of childbearing potential, a negative serum or urine pregnancy test within 14 days prior to registration
Note: Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply
Women < 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy)
Women >= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses > 1 year ago, had chemotherapy-induced menopause with last menses > 1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy)
The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
Patients positive for human immunodeficiency virus (HIV) on effective anti-retroviral
therapy with undetectable viral load within 6 months and a stable regimen of
highly active anti-retroviral (HAART) HIV-positive patients must have no
requirement for concurrent antibiotics or antifungal agents for the prevention
of opportunistic infections

Exclusion Criteria

Metastatic disease invading the liver (> 3 metastases), heart or > 10 metastatic sites detectable after induction systemic therapy. Each visible bone metastasis on radiographic scan count as one site. For site of bony metastases, must order diagnostic CT scan for assessment of response
Intracranial, visible brain metastases on radiographic imaging before induction system therapy is excluded
History of autoimmune disease, including, but not limited to: systemic lupus erythematosus; rheumatoid arthritis; inflammatory bowel disease (e.g. Crohn's, ulcerative colitis); vascular thrombosis associated with antiphospholipid syndrome; Wegener's granulomatosis; Sjogren's syndrome; Guillain-Barre syndrome; multiple sclerosis; vasculitis; or glomerulonephritis. Note: the follow are eligible
Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone are eligible
Prior radiotherapy in the thorax that would result in overlapping radiation therapy (RT) fields, unless the overlapping fields meet dose constraints for this trial
Patients with controlled type 1 diabetes mellitus on a stable insulin regimen are eligible
Patients with eczema, psoriasis, lichen simplex chronicus of 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 not have ocular manifestations within the past year
Rash must cover less than 10% of body surface area (BSA)
Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free
for 5 years prior to randomization. Cancers with a negligible risk of
Disease is well controlled on topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, fluocinolone 0.01%, desonide 0.05%, alclometasone dipropionate 0.05%)
metastasis or death (e.g., expected 5-year OS > 90%) treated with expected
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 or oral steroids)
curative outcome are eligible (such as adequately treated carcinoma in situ of
Severe, active co-morbidity defined as follows
the cervix or oral cavity; localized prostate cancer treated surgically with
Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
curative intent, or ductal carcinoma in situ treated surgically with curative
Active tuberculosis
Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease
intent)
Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen [HBsAg] test and a positive anti-HBc [antibody to hepatitis B core antigen] antibody test) are eligible
Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA). (The HCV RNA test must be performed for patients who have a positive HCV antibody test)
Chronic obstructive pulmonary disease (COPD) requiring chronic oral steroid therapy of > 10 mg prednisone daily or equivalent at the time of registration. Inhaled corticosteroids are not exclusionary
Unstable angina and/or congestive heart failure requiring hospitalization within the last 3 months
History of recent myocardial infarction within 6 months prior to registration
Clinically significant interstitial lung disease
Women who are breastfeeding and unwilling to discontinue
History of allogeneic organ transplant
Patients who have had immunotherapy-induced pneumonitis
Known immunosuppressive disease, for example history of bone marrow transplant or
chronic lymphocytic leukemia (CLL)
Pregnancy: Administration of atezolizumab may have an adverse effect on pregnancy and
poses a risk to the human fetus, including embryo-lethality. Women of child-
bearing potential and men must agree to use adequate contraception (hormonal
or barrier method of birth control; abstinence) prior to study entry, for the
duration of study treatment, 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
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