Pulmonary sarcomatoid_MEDI4736+Treme

• ClinicalTrials.gov Identifier: NCT03022500
• Recruitment Status: Unknown
• First Posted: January 16, 2017
• Last Update Posted: June 7, 2018
• Sponsor: Seoul National University Hospital
• Information provided by (Responsible Party): Bhumsuk Keam, Seoul National University Hospital

Study Description

Brief Summary:

To understand efficacy of Durvalumab(MEDI4736)+ Tremelimumab in Metastatic/relapsed pulmonary sarcomatoid carcinoma

Condition or disease	Intervention/treatment	Phase
Durvalumab + Tremelimumab Combination Treatment, Pulmonary Sarcomatoid Carcinoma, NSCLC	Drug: durvalumab + tremelimumab	Phase 2

Detailed Description:

This is a phase II multi-center, open-label study to evaluate efficacy and safety of durvalumab + tremelimumab combination treatment in patients with pulmonary sarcomatoid carcinoma

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 18 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Durvalumab + Tremelimumab in Pulmonary Sarcomatoid Carcinoma
• Actual Study Start Date: May 18, 2017
• Estimated Primary Completion Date: January 2020
• Estimated Study Completion Date: August 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: durvalumab + tremelimumab; Durvalumab: 1.5g Q4W plusTremelimumab: 75mg Q4W up to 4cycle then Durvalumab 750mg Q2W, till PD or unacceptable toxicity.	Drug: durvalumab + tremelimumab; Durvalumab: 1.5g Q4W plus Tremelimumab: 75mg Q4W up to 4cycle then Durvalumab 750mg Q2W, till PD or unacceptable toxicity.

Outcome Measures

Primary Outcome Measures :

1. Response rate (RR) [ Time Frame: 24month ]
   modified RECIST1.1

Secondary Outcome Measures :

1. Progression-Free Survival (PFS) [ Time Frame: 24month ]
2. Overall Survival (OS) [ Time Frame: 24month ]
3. Toxicity [ Time Frame: 24month ]
   number of patients with treatment-related AE as assessed by NCI CTCAE version 4.0

Other Outcome Measures:

1. biomarker [ Time Frame: 24month ]
   TGS(NGS)

Eligibility Criteria

• Ages Eligible for Study: 20 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Age ≥ 20 years
2. ECOG PS ≤1
3. 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),the patients are eligible)
4. Initial metastatic cases or recurrent cases after curative treatment (any chemotherapy line is allowed)
5. A patient with at least one measurable lesion of which the diameter is confirmed to be ≥ 10mm in spiral CT or multi-detector CT (MD CT), or ≥ 20 mm in conventional CT (it should be used by a consistent method during the study period).
6. If patients have brain metastasis with neurological symptom, they should be stabilized neurologically with prior radiotherapy or surgery for the brain metastasis (no neurologic symptom in progress and without further steroid treatment)
7. Adequate hematologic (neutrophil count ≥ 1,500 cells/mm3, platelets ≥ 100,000 cells/mm3), hepatic (transaminase ≤ upper normal limit(UNL)x2.5, bilirubin level ≤ UNLx1.5), and renal (creatinine ≤ UNL) function
8. A patient with the willingness to comply with the study protocol during the study period and capable of complying with it.
9. A patient who signed the informed consent prior to the participation of the study and who understands that he/she has a right to withdrawal from participation in the study at any time without any disadvantages - Absolute neutrophil count 1,500 cells/mm3, platelets 100,000 cells/mm3
10. Expected survival ≥ 3 months
11. Female subjects must either be of non-reproductive potential (ie, post-menopausal by history: ≥60 years old and no menses for ≥1 year without an alternative medical cause; or history of hysterectomy, or history of bilateral tubal ligation, or history of bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry.

Exclusion Criteria:

1. A patient with no measurable disease
2. chronic systemic steroid therapy or on any other form of immunosuppressive medication
3. has received a live-virus vaccination within 30 days of planned treatment start
4. history of diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction, abdominal carcinomatosis which are known risks factors for bowel perforation
5. active symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis
6. severe hypersensitivity reaction to treatment with another monoclonal antibody (mAb)
7. 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
8. prior treatment with any other anti-programmed cell death protein-1 (anti-PD-1), or PD Ligand-1 (PD-L1) or PD Ligand-2 (PD-L2) agent or anti CTLA4 agents (including durvalumab and tremelimumab)
9. active infection requiring therapy
10. history of Human Immunodeficiency Virus (HIV)
11. active Hepatitis B or C (inactive healthy carriers of HBV with appropriate prophylactic antiviral agents are allowed)
12. symptomatic ascites or pleural effusion
13. pneumonitis that has required a course of oral steroids to assist with recovery, or a history of interstitial lung disease
14. pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study
15. History of active tuberculosis
16. History of allogeneic organ transplant. Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab or tremelimumab, 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
17. Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) ≤ 21 days prior to the first dose of study drug
18. History of allogeneic organ transplant
19. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any subject known to have evidence of acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent
20. Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 180 days after the last dose of durvalumab + tremelimumab combination therapy or 90 days after the last dose of durvalumab monotherapy, whichever is the longer time period

Contacts and Locations

Locations

Korea, Republic of

Department of Internal Medicine, Seoul National University Hospital

Seoul, Korea, Republic of, 110-744

Sponsors and Collaborators

Seoul National University Hospital

Investigators

• Principal Investigator: Bhumsuk Kim, Ph.D.; Seoul National University Hospital

More Information

• Responsible Party: Bhumsuk Keam, Clinical Assistant Professo, Seoul National University Hospital
• ClinicalTrials.gov Identifier: NCT03022500
• Other Study ID Numbers: PSC
• First Posted: January 16, 2017
• Last Update Posted: June 7, 2018
• Last Verified: June 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided
• Plan Description: anticipated as research paper

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Durvalumab; Tremelimumab; Antineoplastic Agents, Immunological; Antineoplastic Agents