Phase II study of durvalumab, doxorub icin, and ifosfamide in pulmonary sarcomatoid carcinoma
- Conditions
- Neoplasms
- Registration Number
- KCT0004531
- Lead Sponsor
- Seoul National University Hospital
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot yet recruiting
- Sex
- All
- Target Recruitment
- 34
1.Patients with histologically confirmed NSCLC with the histology of sarcomatoid carcinoma (WHO criteria for sarcomatoid carcinoma is used; carcinoma with spindle and/or giant cells, pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma, carcinosarcoma, pulmonary blastoma). If the NSCLC patients showed sarcomatoid carcinoma histology in re-biopsy sample (so called epithelial-mesenchymal transition (EMT) phenomenon), such patients are eligible.
2.Age > 20 years at time of study entry.
3.Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
4.Initial metastatic cases or recurrent cases after curative treatment (up to 2 previous lines are allowed, and patients who experienced immune-checkpoint inhibitors are also allowed).
5.A patient with at least one measurable lesion by RECIST1.1.
6.Asymptomatic brain metastasis. If patients have brain metastasis with neurological symptom, they should be stabilized neurologically with prior radiotherapy or surgery for the brain metastasis.
7. Body weight >40kg
8.Adequate normal organ and marrow function as defined below:
?Haemoglobin =9.0 g/dL
?Absolute neutrophil count (ANC) > 1,500 /mm3
?Platelet count =100,000/mm3)
?Serum bilirubin =1.5 x upper limit of normal (ULN).
?AST (SGOT)/ALT (SGPT) =2.5 x ULN unless liver metastases are present, in which case it must be =5x ULN
Measured creatinine clearance (CL) >40 mL/min or Calculated creatinine CL>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976)
9.Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. 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).
10.Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
11.Must have a life expectancy of at least 12 weeks
12.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
1.Participation in another clinical study with an investigational product during the last 3weeks.
2.A patient with no measurable disease.
3.History of diverticulitis, intra-abdominal abscess, gastrointestinal obstruction, abdominal carcinomatosis which are known risks factors for bowel perforation.
4.Active autoimmune disease within the past 2 years (NOTE: Subjects with vitiligo, Grave’s disease, or psoriasis not requiring systemic treatment –within the past 2 years- are not excluded) or a documented history of autoimmune disease or syndrome that requires systemic steroids or immunosuppressive agents.
5.Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies) = 14 days prior to the first dose of study drug If sufficient wash-out time has not occurred due to the schedule or PK properties of an agent, a longer wash-out period will be required, as agreed by AstraZeneca/MedImmune and the investigator.
6.Any unresolved toxicity NCI CTCAE Grade =2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria.
- Patients with Grade =2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
- Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Study Physician.
7.Any concurrent chemotherapy, IP, or biologic therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
8. Major surgical procedure within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.
9. History of allogenic organ transplantation.
10. Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid.
11. 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
12. Uncontrolled current 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 AEs or compromise the ability of t
Study & Design
- Study Type
- Interventional Study
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Response rate
- Secondary Outcome Measures
Name Time Method Progression-Free Survival;Overall Survival;Toxicity