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Phase II trial of atezolizumab (MPDL3280A) plus carboplatin and paclitaxel in patients with metastatic or recurrent thymic carcinoma

Marble study

Takehito Shukuya

Juntendo University Hospital

3-1-3 Hongo, Bunkyo-ku, Tokyo

tshukuya@juntendo.ac.jp

Takehito Shukuya

Juntendo University Hospital

3-1-3 Hongo, Bunkyo-ku, Tokyo

+81-3-3813-3111

tshukuya@juntendo.ac.jp

Not Recruiting

June. 30, 2022

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

(1) Thymic carcinoma diagnosed histologically.
(2) Diagnosed as Masaoka stage III/IVa/IVb ineligible for radical surgery or radiotherapy, or recurrence after radical surgery or radiotherapy.
(3) No history of drug therapy (cytotoxic anticancer drug, immunotherapy, etc.) for thymic carcinoma.
- However, if the subject received postoperative adjuvant chemotherapy after radical surgery or chemoradiotherapy and received cytotoxic anticancer drugs, the subject is eligible if at least 6 months have passed since the last administration of the drug therapy.
(4) Age at the time of enrollment is 20 years or older.
(5) ECOG Performance Status (PS) is 0 - 1 at the time of enrollment.
(6) Patients must have measurable disease according to RECIST version 1.1.
- However, if only a lesion with a history of radiotherapy can be considered as a measurable lesion, the lesion may be considered as a measurable lesion if it shows a clear tendency to enlarge after radiotherapy.
(7) Laboratory tests performed within 14 days prior to registration meet the following criteria (The same day of the week two weeks prior is acceptable based on the registration date. Delay due to national holidays is acceptable).
- Neutrophil count: >=1,500 /mm3
- Hemoglobin: >= 9.0 g/dL
- Platelet count: >=100,000 /mm3
- AST: =<100 IU/L (=<200 IU/L if liver metastases present)
- ALT: =<100 IU/L (=<200 IU/L for liver metastasis)
- Total bilirubin: =<1.5 mg/dL (=<3.0 mg/dL for indirect hyperbilirubinemia)
- Creatinine clearance: >=45 mL/min (estimated by Cockcroft-Gault formula or measured by 24-hour urine storage method. If the estimated value is less than 45 mL/min, the patient is eligible if the measured value by 24-hour urine collection is 45 mL/min or more.)
- SpO2: >=90%.
- PT-INR: =<1.5 (?3.0 if anticoagulation with warfarin is used)
(8) Expected survival of at least 12 weeks.
(9) Patient has received sufficient explanation and understanding of the disease, its symptoms, and the details of this study, and has given written consent to participate in the study.

(1) Active multiple primary neoplasms.
- Duplication of carcinoma in situ (intraepithelial carcinoma) or intramucosal carcinoma that is considered to be cured by local treatment is not included in active multiple primary neoplasms (duplication of carcinoma).
(2) The patient has symptomatic brain metastasis or carcinomatous meningitis.
- If brain metastases are present, the patient is eligible if asymptomatic or if more than 15 days have passed since local treatment and corticosteroids are less than 10 mg/day of prednisolone equivalent.
(3) Patients are eligible if they have undergone local treatment (radiotherapy: within 14 days, major surgery: within 28 days) within the specified number of days prior to enrollment.
- Radiotherapy: 15 days or more, major surgery: 29 days or more
(4) Patient has a local infection requiring drainage or other surgical procedures or an active systemic infection.
(5) Active hepatitis B, hepatitis C, or HIV infection.
- If the patient is HBs antigen negative and HBs antibody or HBc antibody positive, HBV DNA level is measured and the virus level is less than 20 IU/mL (1.3 Log IU/mL), the patient is eligible.
- If the patient is positive for HCV antibody, he/she is excluded.
(6) Patients have interstitial pneumonia that is clearly evident on imaging.
(7) Pleural/pericardial effusions, or ascites requiring treatment.
- Patients with pleural/pericardial effusions, or ascites that do not require continuous drainage or are clinically stable after drainage are eligible.
(8) Patients with autoimmune diseases or with a history of autoimmune diseases requiring corticosteroid therapy.
- However, vitiligo, alopecia, hypothyroidism (if stable with hormone therapy), type 1 diabetes (if stable with hormone therapy), dermatological disease not requiring systemic therapy, inactive disease stable for more than 5 years (requires research administration office confirmation), celiac disease stable with diet therapy only Celiac disease that is stable on diet alone is eligible.
(9) Patients with non-autoimmune diseases requiring continuous systemic administration (oral or intravenous) of corticosteroids at a dose higher than 10 mg/day of prednisolone equivalent, or on immunosuppressive drugs.
(10) Patient has serious complications such as unstable angina pectoris, congestive heart failure, peptic ulcer, cerebral ischemic attack, uncontrolled hypertension, arrhythmia, or diabetes mellitus.
(11) Hypersensitivity to any of the ingredients or additives of carboplatin, paclitaxel, or atezolizumab.
(12) Pregnant women, lactating women, and women with a positive pregnancy test. Men and women who are pregnant, lactating women, and women who have had a positive pregnancy test or who do not intend to use contraception.
(13) Patients who are currently participating in another clinical trial and receiving an investigational drug, or who participated in another clinical trial and received an investigational drug or used an investigational medical device within 8 weeks prior to the first administration of the investigational drug. or patients who have received treatment with a PD-1 pathway inhibitor in the past.
(14) Other patients who are judged to be inappropriate by the investigator or subinvestigator.

Both

patients with metastatic or recurrent thymic carcinoma

- Induction therapy consists of carboplatin (AUC 6 mg/mL/min, day 1) + paclitaxel (200 mg/m2, day 1) + atezolizumab (1,200 mg, day 1) every 3 weeks (every 21 days) for 4 to 6 cycles. (The number of cycles of induction therapy will be determined at the discretion of the investigator or subinvestigator.)
- Patients with no progression on RECIST (other than PD) on post-induction imaging will receive atezolizumab (1,200 mg, day 1) every 3 weeks (every 21 days) for 1 cycle as maintenance therapy.

Objective Response Rate

- Objective Response Rate (ORR) (physician's judgment)
- Disease Control Ratio (DCR) (central image determination)
- Disease Control Ratio (physician's judgment)
- Progression-free survival (PFS) (median image)
- Progression-free survival (judged by physician)
- Duration of response (median imaging)
- Duration of response (physician's judgment)
- Overall Survival (OS)

Yes

If the coordinating physician or the person who conducts the clinical trial judges that secondary use of data obtained in the clinical trial is beneficial for integrated analysis, meta-analysis, etc., the secondary use of data excluding personal information is permitted.

none