Analysis of Survival Status of KRAS Mutation Advanced Non-small Cell Lung Cancer (KILLER)

Analysis of Survival Status of KRAS Mutation Advanced Non-small Cell Lung Cancer Based on NGS Test Results in Hunan Province, China

This study aims to analyze the survival condition of different groups about non-small cell lung cancer patients with KRAS mutations. These groups are made according to the treatment regime, brain metastases and KRAS alterations.

Study Overview

• Status: Recruiting
• Conditions: Non-small Cell Lung Cancer; KRAS G12D; KRAS G12R; KRAS G12V; KRAS G12C; KRAS G12Y; KRAS G13N
• Intervention / Treatment: Drug: Chemotherapy.

Detailed Description

This study aims to analyze the survival condition of different groups about non-small cell lung cancer patients with KRAS mutations. These groups are made according to the treatment regime, brain metastases and KRAS alterations.

All the groups were assessed to chemotherapy, chemotherapy plus immunotherapy, clinical trials etc.

• Study Type: Observational
• Enrollment (Estimated): 1500

Contacts and Locations

• Study Contact: Name: Yongchang Zhang, MD; Phone Number: +8613873123436 +8613873123436; Email: zhangyongchang@csu.edu.cn
• Study Contact Backup: Name: Nong Z Yang, MD; Phone Number: +8613873123436 +8613055193557; Email: yangnong0217@163.com

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410013
      • Recruiting
      • Hunan Cancer Hospital
      • Contact: Yongchang Zhang, MD; Phone Number: +86 731 89762321; Email: zhangyongchang@csu.edu.cn
      • Contact: Nong Yang, MD; Phone Number: +86 731 89762323; Email: yangnong0217@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Advanced non-small cell lung cancer with KRAS mutation confirmed by NGS in Hunan Province, China.

Description

Inclusion Criteria:

1. Understand the requirements and contents of the clinical trial, and provide a signed and dated informed consent form.
2. Age ≥ 18 years.
3. Histopathology or cytology confirmed metastatic non-small cell lung cancer without systemic treatment.
4. KRAS mutations confirmed by an accredited local laboratory.
5. ECOG 0 - 1.
6. Predicted survival ≥ 12 weeks.
7. Adequate bone marrow hematopoiesis and organ function
8. Presence of measurable lesions according to RECIST 1.1.
9. Subjects with stable brain metastases may be included in the study.

Exclusion Criteria:

1. Prior systemic therapy for locally advanced or metastatic disease.

2. Subjects who have received any of the following treatments must be excluded:

   • Treatment with molecules such as EGFR, VEGFR antibodies within 4 weeks prior to the first dose of study drug.
   • Have received radiation within 14 days prior to the first dose or have not recovered from radiation-related toxicity. Chest and extra-brain palliative radiotherapy, stereotactic radiosurgery, and stereotactic body radiotherapy may be performed 7 days prior to the first dose.
   • Ongoing (or inability to discontinue) possibly potent CYP1A2, CYP3A inhibitor (1 week), or inducer (2 weeks) drug therapy or herbal supplements within 1-2 weeks prior to the first dose.
3. Presence of spinal cord compression or meningeal metastasis.
4. History of other malignant tumors within 2 years.
5. Adverse events (except alopecia of any degree) of CTCAE > grade 1 due to prior treatment (e.g., adjuvant chemotherapy, radiotherapy, etc.) prior to the first dose.
6. History of stroke or intracranial hemorrhage within 6 months prior to the first dose.
7. The presence of any severe or poorly controlled systemic disease, including poorly controlled hypertension and active bleeding in the judgment of the investigator.
8. Subjects with persistent or active infection, including but not limited to hepatitis B (HBV), hepatitis C (HCV), human immunodeficiency virus (HIV) and COVID-19 infection.
9. Heart-related diseases or abnormalities
10. Past history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis requiring steroid therapy or interstitial lung disease with active clinical symptoms, immune pneumonia caused by immunotherapy.
11. Refractory nausea and vomiting, chronic gastrointestinal disease, difficulty swallowing drugs, or inability to adequately absorb sunvozertinib or anlotinib due to previous bowel resection.
12. Live vaccine was given 2 weeks before the first medication.
13. Women who are breastfeeding or pregnant.
14. Hypersensitivity to the test drug and the ingredients.
15. Other conditions assessed by the investigator to be unsuitable for participation in the study.

Study Plan

How is the study designed?

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cohorts 1; Non-small cell lung cancer patients with KRAS mutation were treated with chemotherapy.	Drug: Chemotherapy.; pemetrexed, 500mg/m2, ivgtt every 21 day.; Other Names: pemetrexed
Cohorts 2; Non-small cell lung cancer patients with KRAS mutation were treated with chemotherapy plus Immune checkpoint inhibitors.	Drug: Chemotherapy.; pemetrexed, 500mg/m2, ivgtt every 21 day.; Other Names: pemetrexed
Cohorts 3; Non-small cell lung cancer patients with KRAS mutation were treated with chemotherapy, Immune checkpoint inhibitors plus bevacizumab.	Drug: Chemotherapy.; pemetrexed, 500mg/m2, ivgtt every 21 day.; Other Names: pemetrexed
Cohorts 4; Non-small cell lung cancer patients with KRAS mutation were treated from clinical trials.	Drug: Chemotherapy.; pemetrexed, 500mg/m2, ivgtt every 21 day.; Other Names: pemetrexed
Cohorts 5; Non-small cell lung cancer patients with KRAS mutation were not treated for anything.	Drug: Chemotherapy.; pemetrexed, 500mg/m2, ivgtt every 21 day.; Other Names: pemetrexed

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	To assess overall survival, define as first dose to the death of the subject due to any cause.	Time from first subject dose to study completion, or up to 36 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	PFS defines as first dose to first documented disease progression assessed by investigator or death due to any cause.	Time from first subject dose to study completion, or up to 36 months.

Collaborators and Investigators

• Sponsor: Hunan Province Tumor Hospital
• Investigators: Principal Investigator: Yongchang Zhang, MD, zhangyongchang@csu.edu.cn

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2018
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: August 23, 2018
• First Submitted That Met QC Criteria: August 23, 2018
• First Posted (Actual): August 27, 2018

Study Record Updates

• Last Update Posted (Actual): May 31, 2024
• Last Update Submitted That Met QC Criteria: May 29, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Folic Acid Antagonists; Pemetrexed
• Other Study ID Numbers: 20180176

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No