A Prospective Phase II Trial of Pembrolizumab Plus Lenvatinib in Advanced Adrenal Cortical Carcinoma After Failure of Platinum- and Mitotane-Based Chemotherapy (ACCOMPLISH)
- Conditions
- Neoplasms
- Registration Number
- KCT0006789
- Lead Sponsor
- ational Cancer Center
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 30
1.Male/female participants who are at least 19 years of age on the day of signing informed consent with histologically confirmed diagnosis of adrenal cortical carcinoma will be enrolled in this study.
2.Patients with locally advanced, recurrent, or metastatic disease not amenable to surgery, radiotherapy, or combined modality therapy with curative intent.
3.Patients who have received prior systemic therapy including combined mitotane and cisplatin-based chemotherapy as a palliative aim systemic therapy in advanced setting, and have had disease progression within 6 months of the last dose of the most recent systemic therapy. Patients who discontinued prior therapy due to intolerable toxicities can be included.
4.Patients who have refused cytotoxic chemotherapy can be included.
5.Patients should have measurable disease according to RECIST v1.1 meeting the following criteria:
a. at least 1 lesion of =10 mm in the longest diameter for a non-lymph node or =15 mm in the short-axis diameter for a lymph node that is serially measurable according to RECIST using CT or MRI
b. lesions that have had external beam radiotherapy or other loco-regoinal therapies such as radiofrequency ablastion must show subsequent evidence of substantial size increase to be deemed a target lesion.
6.Subject must have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 1
7.Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP=150/90 mmHg at screening and no change in hypertensive medications within 1 week prior to the cycle 1 day 1.
8.Adequate renal function defined as creatinine =1.5 times the upper limit of normal (×ULN) or calculated creatinine clearance =30 ml/min per the Cockcroft and Gault formula
9.Adequate bone marrow function:
a.Absolute neutrophil count (ANC)=1500/mm3 (=1.5×103/µL)
b.platelets=100,000/ mm3 (=100×109/L)
c.hemoglobin=9.0 g/dL
10.adequate blood coagulation function defined by international Normlized Ratio (INR)=1.5 unless participant is receiving anticoagulation therapy
11.adequate liver function defined by:
a.total bilirubin =1.5×ULN except for unconjugated hyperbilirubinemia of Gilbert’s syndrome
b.alkaline phosphatase (ALP), alanine aminotransferase (ALT), and asparate aminotransferase (AST)=3×ULN (in the case of liver metastases =5×ULN), unless there are bone metastases. Subject with ALP values >3×ULN and known to have bone metastases can be included.
12.Life expectancy more than 3 months
13.Patients should agree to discontinue mitotane
14.Females of childbearing potential must agree to use a highly effective method of contraception for the entire study period and for 120 days after study discontinuation (see appendix 7)
15.Male participants who are partners of women of childbearing potential must use a condom plus spermicide and their female partners if of childbearing potential must use a highly effective method of contraception (see inclusion criterion #14 and appendix 7) beginning at least 1 mentrual cycle prior to starting study drugs, throughout the entire study period, and for 120 days after the last dose of study drug, unless the male subjects are totally sexually abstinent or have undergone a successful vasectomy with confirmed azoospermia or unless the female partners have been sterilized surgically or are otherwise proven sterile.
16.Have provided archival tumor tissue sample or newly
1.Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
2.Has received prior therapy with any VEGFR TKI or monoclonal antibody targeting VEGF pathway.
3.Has received major surgery within 2 weeks of start of study intervention. Participants must have recovered from any toxicity and/or complications from major surgery prior to starting therapy.
4.Previous radiotherapy to the only measurable lesion: but previous radiotherapy will be permitted unless the lesion is the only measurable lesion.
5.Subjects having >1+ proteinuria on urinalysis will undergo 24-hour urine collection for quantitative assessment of proteinuria. Subjects with urine protein =1g/24-hour will be ineligible.
6.Gastrointestinal malabsorption, gastrointestinal obstruction, or any other condition that might affect the absorption of lenvatinib.
7.Significant cardiovascular impairment within 6 months of the first dose of study drug. History of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction or stroke, cardiac arrhythmia associated with significant cardiovascular impairment, or a left ventricular ejection fracture (LVEF) below the institutional normal range as determined by MUGA or echocardiogram.
8.Prolongation of QTc interval to >480 msec
9.Bleeding or thrombotic disorders or subjects at risk for severe hemorrhage. The degree of tumor invasion/infiltration of major blood vessels should be considered because of the potential risk of severe hemorrhage associated with tumor shrinkage/necrosis following lenvatinib therapy.
10.Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette–Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
11.Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
12.Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.The use of physiologic doses of corticosteroids may be approved at the discretion of treating physician. In mitotane treated subject, adrenal insufficiency happens inevitably and required dose of corticosteroid is higher than usual due to altered metabolism of corticosteroid.48 Therefore, the decision on whether the dose of maintenance corticosteroid is acceptable for enrollment depends on investigator.
13.Has a known additional malignancy that is progressing or has required active treatment within the past 2 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded. Clinically insignificant or curatively treated localiz
Study & Design
- Study Type
- Interventional Study
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method The primary endpoint of this trial is the ORR. ORR is defined as the proportion of subjects who have complete response or partial response according to RECIST v1.1 criteria
- Secondary Outcome Measures
Name Time Method 1)PFS: The distribution of PFS will be estimated using Kaplan–Meier methodology. Median time to PFS and 95% CI will be provided for each treatment cohort.;2)OS: All events of death will be included, regardless of whether the event occurred while the subject was still taking study drug, or after the subject discontinued study drug. If a subject has no record of death, then the data will be censored at the date the subject was last known to be alive, or the data cutoff date, whichever is earlier. The distribution of OS will be estimated using Kaplan–Meier methodology.