K-SAB Trial - Sotorasib Followed by SBRT to 1-3 Lesions in Advanced NSCLC With KRASG12C Mutation

NCT06127940 | Unknown Phase 1 DMC

• 1 other identifier: K-SAB
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this interventional study is to learn about the combination of sotorasib and stereotactic radiation therapy (SBRT) in patients with metastatic non-small cell lung cancer (NSCLC) with KRASG12C mutations. The main question it aims to answer is: • can SBRT be safely delivered in patients treated with sotorasib Participants will be treated with sotorasib for an 8-week-induction period and if the patient has stable disease or partial response, 1-3 of the remaining lesions will be irradiated with SBRT and sotorasib will then be contiuned after irradiation. The patients will then be followed and evaluated for toxicity to identify if grade 3-5 toxicity attributed to SBRT occurs within 6 months post SBRT. Tumour effects measured according to RECIST v1.1 will also be evaluated.

Conditions

Non-small Cell Lung Cancer Metastatic

Keywords

Stereotactic body radiation therapy; KRAS-G12C mutation; NSCLC

Outcome Measures

Primary Outcomes (1)

• Safety - Grade 3 - 5 toxicity attributed to SBRT

  The number of patients presenting with grade 3-5 toxicity (attributed to SBRT) within 6 months post SBRT.

  6 months post SBRT

Secondary Outcomes (5)

• Progression free survival

  1 year

• Duration of response

  1 year

• Overall survival

  1 year

• Overall toxicity related to SBRT

  1 year

• Overall toxicity related to sotorasib

  1 year

Other Outcomes (1)

• Exploratory outcome

  1 year

Study Arms (1)

Radiotherapy + sotorasib

EXPERIMENTAL

Sotorasib is administered as an 8-week-introduction treatment and if response on a CT-scan is observed (stable disease or partial response), the patient is treated with stereotactic radiation therapy (SBRT) to 1-3 of the remaining lesions.

Radiation: Stereotactic body radiation therapy (SBRT); Drug: Temporary Stopping

Interventions

Stereotactic body radiation therapy (SBRT) RADIATION

SBRT is delivered using institutional standard dosing while sotorasib is withheld during radiation.

Also known as: Sotorasib

Radiotherapy + sotorasib

Temporary Stopping DRUG

Temporary stop of sotorasib during SBRT

Radiotherapy + sotorasib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histological or cytological confirmed advanced NSCLC
• KRASG12C mutation
• Previous at least one line of treatment with immune- or/and chemotherapy or contraindications for immune- and/or chemotherapy.
• Adequate organ function to tolerate sotorasib (see section 6.1 and 6.2 for details)
• lesions technically amenable to SBRT with 15 Gy x 3, 10 Gy x 5, or 7-8 Gy x 5.
• Adequate organ function to tolerate SBRT:
• o Fulfilment of dose constraints to adequate organs at risk
• ECOG performance status (PS) 0-1
• FEV1 ≥1 litre (only applicable for lung targets)
• Age ≥ 18 years
• Measurable lesions according to RECIST

You may not qualify if:

• Leptomeningeal carcinosis (on MRI or in cerebrospinal fluid) or metastases in the central nervous system
• Previous RT for any cancer within the last 3 years possibly interfering with the planned RT within this study
• Life expectancy of less than 6 months
• Inability to understand given information or undergo study procedures according to protocol
• Has evidence or a past medical history of interstitial lung disease or active, non-infectious pneumonitis or known pulmonary fibrosis
• Woman who 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
• Women of childbearing potential (WOCBP) unwilling to use a highly effective method of contraception during treatment and for an additional 7 days after the last dose of sotorasib. WOCBP using hormonal contraceptives should also use a barrier method
• WOCBP with a positive pregnancy test assessed at screening or day 1 by a serum pregnancy test and/or urine pregnancy test
• Centrally located pulmonary target (i.e., within 1 cm of the main bronchi or intermedius bronchus) and targets located within 1 cm of the gut, for SBRT
• 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 study day 1 that was not reviewed and approved by the principal investigator
• 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 study day 1 that was not reviewed and approved by the principal investigator
• Use of proton pump inhibitors (PPIs) within 3 days or H2-receptor antagonists within 1 day prior to study intervention
• Use of warfarin. Use of Direct-Acting Oral Anticoagulants (DOAC) within 14 days or 5 half-lives, whichever is longer, prior to study day 1. Other anticoagulation may be allowed with principal investigator approval.

Sponsors & Collaborators

• Karolinska University Hospital: lead
• Sahlgrenska University Hospital: collaborator
• Amgen: collaborator

Study Sites (1)

Karolinska University Hospital

Stockholm, Solna, 17176, Sweden

RECRUITING

MeSH Terms

Interventions

Radiosurgery; sotorasib; GC Temporary Stopping

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Karin Lindberg, MD, PhD

  Karolinska University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Karin Lindberg, MD, PhD

CONTACT

+46851770000; karin.lindberg@ki.se

Reka Conrad, PhD

CONTACT

+46851770000; reka.conrad@regionstockholm.se

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Model Details: Single arm phase I study

Study Record Dates

• First Submitted: October 4, 2023
• First Posted: November 13, 2023
• Study Start: October 15, 2023
• Primary Completion: June 1, 2025
• Study Completion: January 1, 2026
• Last Updated: November 13, 2023

Record last verified: 2023-11

Locations

SE (1)