Phase II Study of Durvalumab ,Doxorubicin, and Ifosfamide in Pulmonary Sarcomatoid Carcinoma

NCT04224337 | Completed Phase 2

• 1 other identifier: PSC2
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

To evaluate the efficacy and safety of durvalumab in combination with doxorubicin and ifosfamide in patients with PSC.

Conditions

Carcinoma, Non-Small-Cell Lung

Outcome Measures

Primary Outcomes (1)

• Response rate (RR)

  modified RECIST1.1, a percentage and is calculated by dividing the number of patients who achieved a response (complete or partial) by the total number of evaluable patients in the study

  24 months

Secondary Outcomes (3)

• Progression-free survival (PFS)

  24 months

• Overall survival (OS)

  24 months

• Adverse event

  24 months

Other Outcomes (1)

• biomarker

  24 months

Study Arms (1)

Experimental

EXPERIMENTAL

Durvalumab + doxorubicin + ifosfamide

Drug: Durvalumab + doxorubicin + ifosfamide

Interventions

Durvalumab + doxorubicin + ifosfamide DRUG

Durvalumab: 1500mg via IV infusion on day 1 Q3W for 4 cycles followed by durvalumab monotherapy 1500mg via IV infusion Q4W for up to a maximum 12 months Doxorubicin 20mg/m2 via IV infusion on day 1 to day 3 Q3W (up to 4 cycles) Ifosfamide: 1.5g/m2 (with mesna) via IV infusion on day 2 to day 4 Q3W (up to 4cycles)

Experimental

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Age ≥ 20 years at time of study entry.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• 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).
• A patient with at least one measurable lesion by RECIST1.1.
• 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.
• Body weight \>40kg
• 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)
• 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:

You may not qualify if:

• Participation in another clinical study with an investigational product during the last 3weeks.
• A patient with no measurable disease.
• History of diverticulitis, intra-abdominal abscess, gastrointestinal obstruction, abdominal carcinomatosis which are known risks factors for bowel perforation.
• 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.
• Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies) ≤ 3 weeks 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.
• 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.
• 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.
• 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.
• 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.
• 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

Sponsors & Collaborators

• Seoul National University Hospital: lead

Study Sites (1)

Seoul National University Hospital

Seoul, Seoul, South Korea

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

durvalumab; Doxorubicin; Ifosfamide

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Cyclophosphamide; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Bhumsuk Keam, Ph.D.

  Seoul National University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Assistant Professor

Study Record Dates

• First Submitted: January 8, 2020
• First Posted: January 13, 2020
• Study Start: June 11, 2020
• Primary Completion: August 14, 2023
• Study Completion: May 7, 2025
• Last Updated: December 31, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)