Non-Small Cell Lung CancerPhase 2NCT05400577
Sotorasib in KRAS G12C Mutated, Resectable, Stage Ib-IIIA NSCLC
A Phase 2 study testing Sotorasib, 960 mg, oral daily dose for 4 weeks (28 days) in people with Non-Small Cell Lung Cancer, run by Fox Chase Cancer Center at 1 site in United States.
Trial summary
This is a single arm study, conducted at two centers, of neoadjuvant sotorasib in treatment naïve patients with stage Ib-IIIa NSCLC. The study will accrue 25 patients in all. Patients must have been deemed surgically resectable and physiologically fit for surgery by a thoracic surgeon prior to enrollment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Small Cell Lung Cancer
- What is being tested?
- Sotorasib, 960 mg, oral daily dose for 4 weeks (28 days)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Jul 2022to 1 Feb 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have non-squamous NSCLC with KRAS G12C mutation identified through molecular testing (local assessment), AJCC 8 stages Ib, IIa, IIb, IIIa (single nodal station) and assessment by a thoracic surgeon that the patient is potentially resectable and physiologically operable. Lymph nodes should be pathologically staged, if feasible, prior to enrollment.
- No prior NSCLC anticancer therapy
- Must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension in accordance with RECIST criteria v. 1.1 as described in detail in section 11.0.
- Age > 18 years.
- ECOG performance status 0 or 1
- Must have the ability to take oral medications and willing to record daily adherence to investigational product utilizing a sponsor-provided dosing diary
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- Subjects must have normal organ and marrow function as defined below
- Absolute neutrophil count > 1,000/mcL
- Platelets > 75,000/mcL
- Total bilirubin < 1.5 x ULN (< 2.0 x ULN for subjects with documented Gilbert's syndrome or < 3.0 x ULN for whom the indirect bilirubin level suggests an extrahepatic source of elevation)
- AST/ALT (SGOT/SGPT) < 2.5 times institutional normal limits
- Creatinine clearance Estimated glomerular filtration rate based on MDRD (Modification of Diet in Renal Disease) calculation >=30 ml/min/1.73 m2
- Prothrombin time (PT) or partial thromboplastin time (PTT) < 1.5 x ULN, OR International normalized ratio (INR) <1.5 or within target range if on anticoagulation therapy
- Ability to understand and willingness to sign a written informed consent and HIPAA consent document
Who cannot join
- Any prior therapy directed at NSCLC and Previous treatment with a direct KRAS G12C inhibitor.
- Patients receiving any other investigational agents.
- Patients with uncontrolled intercurrent illness, that would in the opinion of the investigator, would pose a risk to subject safety or interfere with the study evaluation, informed consent, procedures, primary endpoint or study completion. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Patients with non-invasive malignancies (e.g. in situ cervical cancer) ARE eligible.
- History of allergic reactions attributed to compound of similar chemical or biologic composition to the agent used in this study.
- Patients receiving any medications or substances that are strong inhibitors or inducers of sotorasib ineligible. Please refer to section 5.2 for details about excluded therapies and restrictions.
- Major surgery (as assessed by treating clinician) within 28 days of study registration.
- Pregnant or breast feeding. Refer to section 4.4 for further detail.
Trial locations and contacts
1 site in 1 country.
United States1 site
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
About this study
Official title: Neoadjuvant Sotorasib in KRAS G12C Mutated, Resectable, Stage Ib-IIIA Non-Small Cell Lung Cancer (NSCLC)
This is a single arm study, conducted at two centers, of neoadjuvant sotorasib in treatment naïve patients with stage Ib-IIIa NSCLC. The study will accrue 25 patients in all. Patients must have been deemed surgically resectable and physiologically fit for surgery by a thoracic surgeon prior to enrollment.
Read the detailed description
There will be a two-part consent, including consent for KRAS testing and consent for treatment on trial. Testing for a KRAS G12C mutation in patients with resectable, stage Ib-IIIa NSCLC is currently not standard of care. Patients who are otherwise felt to be good candidates for this study, after review in multidisciplinary thoracic tumor board, will be screened for KRAS G12C after signing informed consent for screening. Next generation sequencing will be performed on standard of care diagnostic biopsy tissue for EGFR (standard of care) as well as KRAS mutations. Patients who are found to have a KRAS G12C mutation, will be eligible for the study intervention.
This is a single arm study, conducted at two centers, of neoadjuvant sotorasib in treatment naïve patients with stage Ib-IIIa NSCLC. The study will accrue 25 patients in all. Patients must have been deemed surgically resectable and physiologically fit for surgery by a thoracic surgeon prior to enrollment. In addition, every patient will be discussed in multidisciplinary thoracic tumor board prior to enrollment, with medical oncology, radiation oncology and surgical oncology physicians present, to determine the optimal treatment approach. All patients must undergo baseline tumor staging, including pretreatment biopsy, pathological evaluation of mediastinal lymph nodes (if indicated) by means of bronchoscopy or mediastinoscopy, chest and brain imaging (CT chest with contrast and CT head with contrast or MRI brain); PET and diagnostic CT chest will be repeated within 7 days before surgery. Subjects will take sotorasib dosed at 960 mg daily by mouth with or without food for 4 weeks (28 days) prior to surgery. Changes in tumor size will be evaluated by Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. The primary objective of this study is to determine the rate of MPR. Primary tumors will be assessed, using the recently published International Association for the Study of Lung Cancer guidelines, for percentage of residual viable tumor identified on routine hematoxylin and eosin (H\&E) staining, and tumor with no more than 10% viable tumor cells will be considered to have a MPR.
Once patients have completed neoadjuvant therapy, they will undergo surgery, followed by standard of care adjuvant therapy as deemed fit by their treating physician. Data on disease assessment during patients' standard of care visits post-surgery will be collected to evaluate their DFS. All patients will be accrued in 18 months.
- Conditions
- Non-Small Cell Lung Cancer
- Being tested
- Sotorasib, 960 mg, oral daily dose for 4 weeks (28 days)
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sotorasib, 960 mg, oral daily dose for 4 weeks (28 days)Drug
Sotorasib, 960 mg, oral daily dose for 4 weeks (28 days)
| Study group | Role | What they receive |
|---|---|---|
| Sotorasib, 960 mg, oral daily dose for 4 weeks (28 days) | Experimental | Not described Receives: Drug: Sotorasib, 960 mg, oral daily dose for 4 weeks (28 days) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Major pathologic response
Major pathologic response is defined as a resection specimen with < or = to 10% viable tumor cells in patients treated with neoadjuvant sotorasib for KRAS G12C mutated, stage Ib-IIIa NSCLC
Measured: 2 months
Secondary outcomes (1)
Determine the safety, feasibility and tolerability of neoadjuvant sotorasib therapy in patients with surgically resectable KRAS G12C mutant NSCLC
Safety is assessed by all treatment-emergent adverse events and treatment-related adverse events. All adverse events will be assessed by the NCI CTCAE v5.0.
Measured: 1 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jun 2022
- Study start13 Jul 2022
- Primary completion1 Jan 2024 (estimated)
- Study completion1 Feb 2024 (estimated)
Why it stopped: Grantor withdrew support due to slow accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-Small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by Fox Chase Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fox Chase Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Hossein Borghaei, DO, Principal investigator, Fox Chase Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05400577
- Sponsor's protocol ID
- TH-180
- Status last verified
- Jul 2023
- First submitted
- 29 Apr 2022
- Last updated
- 17 Jul 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neoadjuvant Sotorasib in KRAS G12C Mutated, Resectable, Stage Ib-IIIA Non-Small Cell Lung Cancer (NSCLC)
- ClinicalTrials.gov ID
- NCT05400577
- Acronym / sponsor ID
- TH-180
- Conditions
- Non-Small Cell Lung Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Grantor withdrew support due to slow accrual
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Fox Chase Cancer CenterUniversity, hospital or other
- Study start
- 13 Jul 2022 (actual)
- Primary completion
- 1 Jan 2024 (estimated)
- Study completion
- 1 Feb 2024 (estimated)
- First posted
- 1 Jun 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a single arm study, conducted at two centers, of neoadjuvant sotorasib in treatment naïve patients with stage Ib-IIIa NSCLC. The study will accrue 25 patients in all. Patients must have been deemed surgically resectable and physiologically fit for surgery by a thoracic surgeon prior to enrollment.
Detailed description
There will be a two-part consent, including consent for KRAS testing and consent for treatment on trial. Testing for a KRAS G12C mutation in patients with resectable, stage Ib-IIIa NSCLC is currently not standard of care. Patients who are otherwise felt to be good candidates for this study, after review in multidisciplinary thoracic tumor board, will be screened for KRAS G12C after signing informed consent for screening. Next generation sequencing will be performed on standard of care diagnostic biopsy tissue for EGFR (standard of care) as well as KRAS mutations. Patients who are found to have a KRAS G12C mutation, will be eligible for the study intervention.
This is a single arm study, conducted at two centers, of neoadjuvant sotorasib in treatment naïve patients with stage Ib-IIIa NSCLC. The study will accrue 25 patients in all. Patients must have been deemed surgically resectable and physiologically fit for surgery by a thoracic surgeon prior to enrollment. In addition, every patient will be discussed in multidisciplinary thoracic tumor board prior to enrollment, with medical oncology, radiation oncology and surgical oncology physicians present, to determine the optimal treatment approach. All patients must undergo baseline tumor staging, including pretreatment biopsy, pathological evaluation of mediastinal lymph nodes (if indicated) by means of bronchoscopy or mediastinoscopy, chest and brain imaging (CT chest with contrast and CT head with contrast or MRI brain); PET and diagnostic CT chest will be repeated within 7 days before surgery. Subjects will take sotorasib dosed at 960 mg daily by mouth with or without food for 4 weeks (28 days) prior to surgery. Changes in tumor size will be evaluated by Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. The primary objective of this study is to determine the rate of MPR. Primary tumors will be assessed, using the recently published International Association for the Study of Lung Cancer guidelines, for percentage of residual viable tumor identified on routine hematoxylin and eosin (H\&E) staining, and tumor with no more than 10% viable tumor cells will be considered to have a MPR.
Once patients have completed neoadjuvant therapy, they will undergo surgery, followed by standard of care adjuvant therapy as deemed fit by their treating physician. Data on disease assessment during patients' standard of care visits post-surgery will be collected to evaluate their DFS. All patients will be accrued in 18 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sotorasib, 960 mg, oral daily dose for 4 weeks (28 days) | Experimental | Drug: Sotorasib, 960 mg, oral daily dose for 4 weeks (28 days) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Patients must have non-squamous NSCLC with KRAS G12C mutation identified through molecular testing (local assessment), AJCC 8 stages Ib, IIa, IIb, IIIa (single nodal station) and assessment by a thoracic surgeon that the patient is potentially resectable and physiologically operable. Lymph nodes should be pathologically staged, if feasible, prior to enrollment.
- No prior NSCLC anticancer therapy
- Must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension in accordance with RECIST criteria v. 1.1 as described in detail in section 11.0.
- Age > 18 years.
- ECOG performance status 0 or 1
Key exclusion criteria (7 listed)
- Any prior therapy directed at NSCLC and Previous treatment with a direct KRAS G12C inhibitor.
- Patients receiving any other investigational agents.
- Patients with uncontrolled intercurrent illness, that would in the opinion of the investigator, would pose a risk to subject safety or interfere with the study evaluation, informed consent, procedures, primary endpoint or study completion. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Patients with non-invasive malignancies (e.g. in situ cervical cancer) ARE eligible.
- History of allergic reactions attributed to compound of similar chemical or biologic composition to the agent used in this study.
- Patients receiving any medications or substances that are strong inhibitors or inducers of sotorasib ineligible. Please refer to section 5.2 for details about excluded therapies and restrictions.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sotorasib, 960 mg, oral daily dose for 4 weeks (28 days)Sotorasib, 960 mg, oral daily dose for 4 weeks (28 days) | Drug | Sotorasib, 960 mg, oral daily dose for 4 weeks (28 days) |
Primary outcome
Major pathologic response
Time frame: 2 months
Major pathologic response is defined as a resection specimen with < or = to 10% viable tumor cells in patients treated with neoadjuvant sotorasib for KRAS G12C mutated, stage Ib-IIIa NSCLC
1 secondary outcome
Determine the safety, feasibility and tolerability of neoadjuvant sotorasib therapy in patients with surgically resectable KRAS G12C mutant NSCLC
Time frame: 1 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hossein Borghaei, DO principal investigator
Fox Chase Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sotorasib, 960 mg, oral daily dose for 4 weeks (28 days) in people with Non-Small Cell Lung Cancer, run by Fox Chase Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 17 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Major pathologic response (time frame: 2 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jul 2023.