Durvalumab and Tremelimumab in Combination with Platinum-based Chemotherapy for the Treatment of Patients with Untreated Extensive-Stage Small Cell Lung Cancer
- For Nebraska, age of consent is >=19 years old
- Histologically or cytologically confirmed ES-SCLC
- Tumor biopsy or cytology should be obtained within 8 weeks of initiation of treatment
- Brain metastases; must be asymptomatic or treated and stable, off steroids for at least 1 month prior to study treatment (one month time frame needed due to the high dose of steroids needed to treat these type of patients)
- Have not received any prior therapy for small cell lung cancer (SCLC), except palliative radiation. If the patient received radiation, there must be measurable disease outside the radiation field
- Measurable disease or evaluable disease based on RECIST version 1.1
- Eastern Cooperative Oncology Group (ECOG) = 2
- Body weight > 30 kg
- No active secondary malignancy. Patients with other prior malignancies will be included, provided they have been disease-free for at least five years
- Absolute neutrophil count (ANC) >= 1,500/ul (within 7 days prior to starting treatment)
- Platelet count >= 100,000/mm^3 (within 7 days prior to starting treatment)
- Hemoglobin >= 9.0 g/dL (within 7 days prior to starting treatment)
- Serum creatinine less than 1.5 times the upper limits of normal (within 7 days prior to starting treatment)
- Measured creatinine clearance (CL) > 40 mL/min (within 7 days prior to starting treatment) or calculated creatinine clearance CL > 40 mL/min by the Cockcroft-Gault formula or by 24-hour urine collection for determination of creatinine clearance (within 7 days prior to starting treatment)
- Serum aspartate transaminase (AST) and alanine transferase (ALT) less than 1.5 times the upper limits of normal (within 7 days prior to starting treatment in the absence of liver metastasis)
- Serum alkaline phosphatase less than 2.5 times the upper limits of normal (within 7 days prior to starting treatment in the absence of liver metastasis)
- Serum bilirubin =< 1.5 X institutional upper limit of normal (ULN) (within 7 days prior to starting treatment in the absence of liver metastasis)
- In the presence of liver metastasis, hepatic function (serum AST, ALT and alkaline phosphatase less than or equal to 5.0 times the upper limits of normal) (within 7 days prior to starting treatment)
- Women of childbearing potential must have a pregnancy test (urine or serum) proven negative within 14 days prior to registration. Evidence of post-menopausal status or 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)
- Able to comply with the protocol for the duration of the study, which includes undergoing treatment, attending all scheduled visits
- Able to return for treatment and follow-up visits as specified in the protocol including treatment, scheduled visits, and examinations including follow up
- Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization (e.g., Health Insurance Portability and Accountability Act in the US, European Union [EU] Data Privacy Directive in the EU) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations
- Participation in another clinical study with an investigational product during the last 28 days
- Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
- Any previous chemotherapy and /or immunotherapy for SCLC
- Any live attenuated vaccine =< 30 days before first doses of study drugs. * Note: Patients, if enrolled, should not receive live vaccine whilst receiving investigational product (IP) and up to 30 days after the last dose of IP
- Current or prior use (=< 14 days before first doses of study drugs) of immunosuppressive medication. The following are exceptions to this criterion: * Intranasal/inhaled corticosteroids topical steroids, or local steroid injections (e.g., intra articular injection) * Systemic corticosteroids =< 10 mg prednisone equivalent * Steroids as premedication for hypersensitivity reactions (e.g., computed tomography [CT] scan premedication)
- Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment * Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable
- Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP * Note: Local surgery of isolated lesions for palliative intent is acceptable
- History of allogenic organ transplantation
- History of another primary malignancy except for: * Malignancy treated with curative intent and with no known active disease >= 5 years before the first dose of IP and of low potential risk for recurrence * Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease * Adequately treated carcinoma in situ without evidence of disease
- History of leptomeningeal carcinomatosis
- Paraneoplastic syndrome (PNS) of autoimmune nature, requiring systemic steroids or clinical symptomatology suggesting worsening of PNS
- Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis [TB] testing in line with local practice), human immunodeficiency virus (HIV) (positive HIV 1/2 antibodies), hepatitis B (known positive HBV surface antigen [HBsAg] result) and C * Patients with a past or resolved hepatitis B virus (HBV) infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible * Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA)
- Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.]). The following are exceptions to this criterion: * Patients with vitiligo or alopecia * Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement * Any chronic skin condition that does not require systemic therapy * Patients without active disease in the last 5 years may be included but only after consultation with the study physician * Patients with celiac disease controlled by diet alone
- Uncontrolled intercurrent illness, including but not limited to ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring adverse events (AEs) or compromise the ability of the patient to give written informed consent
- History of active primary immunodeficiency
- Any patient, in the opinion of the treating physician, will not be able to tolerate treatment or the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions and requirements
- Pregnancy, breastfeeding or planning to be pregnant or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy (cohort 1) or 180 days after the last dose of durvalumab + tremelimumab combination therapy (cohort 2)
- Known allergies, hypersensitivity, or intolerance to any of the study medications, excipients, or similar compounds
- Prior randomization or treatment in a previous durvalumab and/or tremelimumab clinical study regardless of treatment arm assignment
I. Evaluate the safety and tolerability profile of durvalumab plus (+) tremelimumab in combination with carboplatin and etoposide in extensive-stage small cell lung cancer (ES-SCLC) and performance status of 2 (PS2) based on the percentage of grade 3 or higher dose-limiting toxicities.
I. Overall survival (OS).
II. Progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
III. Objective response rate (ORR) according to RECIST 1.1.
IV. Duration of response (DOR).
V. Changes in Eastern Cooperative Oncology Group (ECOG) performance status.
VI. Characterize the immunogenicity of durvalumab + tremelimumab.
VII. Health-related quality of life (QOL) measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30).
OUTLINE: If the Cohort 1 treatment is found to be tolerable, patients will be assigned to Cohort 2.
COHORT I: Patients receive carboplatin intravenously (IV) on day 1 and etoposide IV on days 1, 2, and 3. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. With cycles 3 and 4, patients also receive durvalumab IV over 1 hour on day 1. Treatment with durvalumab repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.
COHORT II: Patients receive carboplatin IV on day 1 and etoposide IV on days 1, 2, and 3. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. With cycles 3 and 4, patients also receive tremelimumab IV over 1 hour and durvalumab IV over 1 hour on day 1. Treatment with durvalumab and tremelimumab continues every 3 weeks for another 2 cycles (cycles 5 and 6) after end of carboplatin and etoposide treatment. After cycle 6, patients receive durvalumab IV over 1 hour every 4 weeks in the absence of disease progression or unacceptable toxicity.
Trial Phase Phase I
Trial Type Treatment
University of Nebraska Medical Center
- Primary ID 275-19
- Secondary IDs NCI-2020-01503
- Clinicaltrials.gov ID NCT03963414