CODEBREAK-IGR: Sotorasib in Previously Treated Locally Advanced or Metastatic NSCLC Subjects With Mutated KRAS p.G12C
Study Details
Study Description
Brief Summary
This study aims to provide a comprehensive understanding of sotorasib's mechanisms of action and resistance in NSCLC patients.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Sotorasib treatment Sotorasib : 120 mg, once a day, per os, until progression, unacceptable toxicity, death or lost to follow-up |
Drug: Sotorasib 120Mg Tab
Daily sotorasib treatment until progression, unacceptable toxicity, death, or lost to follow-up
|
Outcome Measures
Primary Outcome Measures
- Tumor response assessment [at 4 months after treatment start]
To evaluate tumor response at 4 months and decipher relevant biomarkers associated with primary (progression within the first 4 months) and acquired resistance to sotorasib (progression after 4 months).
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age higher than 18 years;
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ECOG less or equal to 1 at the time of screening;
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Pathologically documented, previously treated, locally-advanced and unresectable or metastatic NSCLC with KRAS p.G12C mutation confirmed through molecular testing (results of both tissue and liquid biopsy are accepted);
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Subjects will have progressed or experienced disease recurrence on or after receiving at least 1 prior systemic therapy for locally advanced and unresectable or metastatic disease.
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Life expectancy of longer than 3 months from the time of screening, in the opinion of the investigator;
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Patients must have lesions easily accessible to biopsy and must have accepted to perform pre-treatment, on-treatment and end-of-treatment biopsies;
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Have adequate bone marrow reserve and organ function, based on local laboratory data within 14 days prior to registration
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Patients must understand, sign and date the written informed consent from prior to any protocol-specific procedures performed.
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Patients should be able and willing to comply with study visits and procedures as per protocol.
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Patients must be affiliated to a Social Security System or beneficiary of the same.
Exclusion Criteria:
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Patient unwilling to participate to the biological investigations and to perform biopsies and blood sample collection as required in the protocol;
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Use of known cytochrome P450 (CYP) 3A4 or P-gp sensitive substrates (with a narrow therapeutic window), within 14 days or 5 half-lives of the drug or its major active metabolite, whichever is longer, prior to registration, that was not reviewed and approved by the principal investigator.
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Use of strong inducers of CYP3A4 (including herbal supplements such as St. John's wort) within 14 days or 5 half-lives (whichever is longer) prior to registration, that was not reviewed and approved by the principal investigator.
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Inadequate washout period prior to registration, defined as: Any cytotoxic chemotherapy, investigational agents or other anticancer drug(s) from a previous cancer treatment regimen or clinical study shorter than 14 days or 5 half-lives;
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Prior treatment with a KRAS inhibitor.
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Major surgery within 28 days of registration.
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Significant gastrointestinal disorder that results in significant malabsorption, requirement for intravenous alimentation, or inability to take oral medication.
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Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within 6 months prior to registration, unstable arrhythmias or unstable angina.
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Severe infections within 2 weeks prior to registration, but not limited to hospitalization for complications of infection, bacteremia or severe pneumonia. Prophylactic antibiotics are allowed.
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Baseline or unresolved pneumonitis from prior treatment;
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Current CTCAE version 5.0 grade higher or equal to 2 peripheral neuropathy.
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Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures at a frequency greater than monthly. Subjects with PleurX catheters in place may be considered for the study with Principal Investigator approval.
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Known history of Human Immunodeficiency Virus (HIV) infection
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Exclusion of hepatitis infection based on the following results and/or criteria:
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Positive hepatitis B surface antigen (HepBsAg) (indicative of chronic Hepatitis B or recent acute hepatitis B)
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Negative HepBsAg with a positive for hepatitis B core antibody (Hepatitis B core antibody testing is not required for screening, however if this is done and is positive, then hepatitis B surface antibody [Anti-HBs] testing is necessary.
Undetectable anti-HBs in this setting would suggest unclear and possible infection, and needs exclusion).
- Positive Hepatitis C virus antibody: Hepatitis C virus RNA by polymerase chain reaction is necessary. Detectable Hepatitis C virus RNA renders the subject ineligible.
- Leptomeningeal disease and active brain metastases. Subjects who have had brain metastases resected or have received whole brain radiation therapy or stereotactic radiosurgery ending at least 2 weeks prior to registration are eligible if they meet all of the following criteria:
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residual neurological symptoms grade less or equal to 2;
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on stable doses of dexamethasone or equivalent for at least 2 weeks, if applicable; and
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follow-up brain imaging performed within 30 days of enrollment shows no progression or new lesions appearing.
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Female subject is pregnant or breastfeeding or planning to become pregnant or breastfeed during treatment and for an additional 7 days after the last dose of sotorasib or during treatment if planning to become pregnant.
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Female subjects of childbearing potential unwilling to use 1 highly effective method of contraception during treatment and for an additional 7 days after the last dose of sotorasib
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Female subjects of childbearing potential with a positive pregnancy test assessed at Screening or day 1 by a serum pregnancy test and/or urine pregnancy test.
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Male subjects with a female partner of childbearing potential who are unwilling to practice sexual abstinence (refrain from heterosexual intercourse) or use contraception during treatment and for an additional 7 days after the last dose of sotorasib
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Male subjects with a pregnant partner who are unwilling to practice abstinence or use a condom during treatment and for an additional 7 days after the last dose of sotorasib
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Male subjects unwilling to abstain from donating sperm during treatment and for an additional 7 days after the last dose of investigational product.
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Any evidence of primary malignancy other than locally advanced or metastatic lung cancer at within 3 years of registration, except adequately resected non-melanoma skin cancer, curatively treated in-situ disease, or other solid tumors curatively treated;
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Participation in another clinical trial evaluating an experimental drug (except non-interventional research).
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Patient under guardianship or deprived of his liberty by a judicial or administrative decision or incapable of giving its consent.
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Hypersensitivity to the active substance or to any excipient
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Patients with hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Centre Léon Bérard | Lyon | France | 69373 | |
| 2 | AP-HM Hôpital Nord | Marseille | France | 13015 | |
| 3 | AP-HP Hôpital Tenon | Paris | France | 75020 | |
| 4 | Gustave Roussy | Villejuif | France | 94800 |
Sponsors and Collaborators
- Gustave Roussy, Cancer Campus, Grand Paris
Investigators
- Principal Investigator: Mihaela ALDEA, MD, Gustave Roussy, Cancer Campus, Grand Paris
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2021-006958-31
- 2021/3401