Health TrialsbyHealthPanel

Carfilzomib in Combination With Sotorasib for the Treatment of Patients With KRAS G12C Mutated Advanced or Metastatic Non-small Cell Lung Cancer

ConditionsAdvanced Lung Non-Small Cell CarcinomaMetastatic Lung Non-Small Cell CarcinomaStage III Lung Cancer AJCC v8Stage IV Lung Cancer AJCC v8
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorCity of Hope Medical Center

About this trial

This phase I trial tests the safety, side effects, and best dose of carfilzomib in combination with sotorasib in treating patients with KRAS G12C-mutated non-small cell lung cancer (NSCLC) that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). Carfilzomib is a drug that binds to and inhibits the activity of the protein complex that is responsible for degrading other damaged or unneeded proteins. The inhibition of this protein by carfilzomib can then cause tumor growth inhibition and cell death. Sotorasib is a drug that binds to and inhibits the activity of the KRAS G12C mutant. This may inhibit growth in KRAS G12C-expressing tumor cells. Combining carfilzomib and sotorasib may be a safe and effective treatment option for patients with KRAS G12C-mutated advanced or metastatic NSCLC.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Documented informed consent of the participant and/or legally authorized representative

Age: ≥ 18 years

Eastern Cooperative Oncology Group (ECOG) ≤ 2

Histologically confirmed NSCLC that is metastatic or advanced. The tumor must exhibit evidence of KRASG12C mutation which is determined by either a Clinical Laboratory Improvement Act (CLIA) certified ctDNA assay or by a CLIA certified tumor tissue assay

Disqualifiers

Chemotherapy or immunotherapy within 21 days prior to day 1 of protocol therapy

Radiation therapy within 14 days prior to day 1 of protocol therapy

KRAS inhibitor within 14 days prior to day 1 of protocol therapy

Investigational therapy within 28 days prior to day 1 of protocol therapy (or 5 half-lives, use whichever is shorter)

Trial design

Design model

Single group

Treatments tested in this trial

  • Biopsy

    Procedure/Surgery

    Undergo biopsy

  • Biospecimen Collection

    Procedure/Surgery

    Undergo collection of blood samples

  • Carfilzomib

    Drug

    Given IV

  • Computed Tomography

    Procedure/Surgery

    Undergo CT

  • Echocardiography

    Procedure/Surgery

    Undergo ECHO

  • Magnetic Resonance Imaging

    Procedure/Surgery

    Undergo MRI

  • Sotorasib

    Drug

    Given PO

Treatment groups

15 Participants
are divided into 1 treatment group
Group A: Treatment (carfilzomib, sotorasib)Experimental treatment 7 interventions

Trial outcomes

Primary outcomes

1

Incidence of dose limiting toxicities

The incidence of dose-limiting toxicities during cycle 1 will be used to determine the maximum tolerated dose and the recommended phase II dose of the comibination of carfilzomib and sotorasib. Will be described and graded at all dose levels using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0.

Time frame
During cycle 1 (each cycle is 28 days)
2

Incidence of grade 3 and 4 treatment-related toxicities

Grade 3 and 4 adverse events will be described and graded at all dose levels using the NCI CTCAE v5.0.

Time frame
Up to 30 days after completion of study treatment

Secondary outcomes

1

Objective response rate

Defined as the proportion of all subjects with confirmed partial response or complete response, according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Response rate will be summarized by frequencies and percentages, along with the corresponding exact 95% confidence intervals.

Time frame
From the start of treatment until disease progression/recurrence, assessed up to 30 days after completion of study treatment
2

Duration of response

Will be estimated using the Kaplan-Meier method.

Time frame
From treatment response to progression or death, assessed up to 30 days after completion of study treatment
3

Progression-free survival

Disease progression will be defined using RECIST version 1.1. Will be estimated using the Kaplan-Meier method.

Time frame
From day 1 of treatment until the criteria for disease progression is met or until death, assessed up to 30 days after completion of study treatment
4

Overall survival

Will be estimated using the Kaplan-Meier method.

Time frame
From the date of study enrollment to the date of death, assessed up to 30 days after completion of study treatment

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

City of Hope Medical Center

Lead sponsor

National Cancer Institute (NCI)

Collaborator

Source ClinicalTrials.gov
Apply now