A Trial Comparing Selpercatinib to Chemotherapy in Patients with Non-Small Cell Lung Cancer
- Conditions
- Male or female patients with advanced, treatment-naïve RET Fusion-Positive Non-Squamous NSCLCMedDRA version: 21.1Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-001979-36-GR
- Lead Sponsor
- Eli Lilly and Company
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 261
1.Histologically or cytologically confirmed Stage IIIB-IIIC or Stage IV NSCLC that is not suitable for radical surgery or radiation therapy. The histology of the tumor must be predominantly nonsquamous. Squamous cell and/or mixed small cell/nonsmall cell histology is not permitted.
2.Must have a RET gene fusion in tumor using PCR or NGS. Results in blood using NGS are also acceptable.
•The RET gene fusion result should be generated from a laboratory with CLIA, ISO/IEC, CAP, or other similar certification that clearly denotes the presence of a RET alteration. Blood results must be determined on a platform that meets these standards and is also Lilly approved.
•In all cases, the presence of the RET fusion must be confirmed upon review of the pathology report by Lilly or designee prior to enrollment.
3.Must have measurable disease per RECIST 1.1 as assessed by the investigator. Target lesions situated in a previously irradiated area are considered measurable if progression has been determined in such lesions, and the location of previously irradiated lesions is clearly documented.
4.Must have Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2.
5.Must have life expectancy of at least 3 months.
6.Must have adequate organ function, as defined subsequently. These values must be met during the baseline visit prior to randomization.
7.Ability to swallow capsules.
Contraception
8.Men with partners of childbearing potential or women of childbearing potential must agree to use a highly effective contraceptive method (e.g., intrauterine device or birth control pill) during treatment with study drug and for 6 months following the last dose of study drug. In addition, male subjects on selpercatinib should use a condom while on study treatment and males randomized to Arm B should use a condom while on study treatment and for 91 days following the last dose of pemetrexed.
Note: Unless not allowed by local regulations, women of childbearing potential who are abstinent (if this is complete abstinence, as their preferred and usual lifestyle) or in a same-sex relationship (as part of their preferred and usual lifestyle) must agree to either remain abstinent or stay in a same-sex relationship without sexual relationships with males. Periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods), declaration of abstinence just for the duration of a trial, and withdrawal are not acceptable methods of contraception.
9.Women of childbearing potential must:
•Have a negative pregnancy test (serum or urine, consistent with local regulations) documented within 24 hours prior to treatment with study drug.
•Not be breast-feeding during treatment and for at least 4 months after the last dose of study drug.
Informed consent
10.The participant must be capable of demonstrating an understanding of the nature, significance, and implications of participation in the trial and giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
Age
11.Are of an acceptable age to provide informed consent according to local regulations and are at least 18 years of age.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 125
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 125
1.Have additional validated oncogenic drivers in NSCLC, if known.
2.Have symptomatic central nervous system (CNS) metastases, carcinomatous meningitis, or untreated spinal cord compression. Any previous definitive treatment or glucocorticoid therapy to treat CNS metastases must be completed at least 2 weeks prior to randomization and patients must be neurologically stable for 2 weeks prior to randomization.
3.Have clinically significant active cardiovascular disease or history of myocardial infarction within 6 months prior to planned start of study treatment or prolongation of the QT interval corrected for heart rate using Fridericia’s formula (QTcF) >470 msec on more than 1 ECG obtained during the baseline period.
4.Have uncontrolled, disease-related, pericardial effusion or pleural effusion.
5.Have a history of human immunodeficiency virus ([HIV]; known HIV 1/2 antibodies positive). If the medical history, symptoms, and/or laboratory values suggest the patient may have HIV, appropriate assessments should be conducted to determine if the patient should be excluded.
6.Have known active Hepatitis B or C.
7.Have active, uncontrolled, systemic bacterial, viral, or fungal infection that requires treatment or have serious ongoing intercurrent illness that is not controlled, despite optimal treatment. Screening for chronic conditions is not required.
8.Have clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal absorption of the study drug.
9.Other malignancy unless nonmelanoma skin cancer, carcinoma in situ of the cervix or other in situ cancers, or a malignancy diagnosed =2 years previously and not currently active. Patients receiving adjuvant hormone therapy for breast or prostate cancer with no evidence of disease are eligible.
10.Has had any of the following prior to randomization:
•Prior systemic therapy for metastatic disease. Patients who received adjuvant or neoadjuvant therapy are eligible if the last dose of the systemic treatment was completed at least 6 months prior to randomization.
•Major surgery within 3 weeks prior to planned start of study treatment.
•Radiotherapy for palliation within 1 week of the first dose of study treatment or any radiotherapy within 6 months prior to the first dose of study treatment if more than 30 Gy to the lung.
•Any unresolved toxicities from prior therapy greater than Common Terminology Criteria in Adverse Events (CTCAE) Grade 1 at the time of starting study treatment except for alopecia and Grade 2, prior therapy related neuropathy.
11.Are taking a concomitant medication that is known to cause QTc prolongation
12.Require chronic treatment with steroids. Intermittent use of inhaled steroids for asthma or local steroid injections is allowed. Replacement therapy is not considered a form of chronic treatment and does not need to be excluded. However, immunosuppressive therapy within 1 week prior to the first dose of study medication is not permitted.
13.Have received a live vaccine within 30 days prior to the first dose of trial treatment. Seasonal flu vaccines that do not contain live virus are permitted.
14.Are unable to interrupt nonsteroidal anti-inflammatory drugs (NSAIDs) 2 days before (5 days for long-acting NSAIDs), the day of, and 2 days following administration of pemetrexed.
15.Are currently enrolled in any other clinical study involving an investigational product or any other type of medical research j
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method