Clinical trial NCT04059874: Treatment of Non-small Cell Lung Cancer With PD-1 Monoclonal Antibody Combined With Donafenib Toluene Sulfonate
Official title: To Assess the Safety and Efficacy of Third-line and Above Therapy of Patients With Local Advanced or Metastatic NSCLC With Combined Treatment With Launched Recombinant Humanized Anti-PD-1 Monoclonal Antibody and Donafenib Tosilate
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Non-small Cell Lung Cancer
Keywords: non-small cell lung cancer
Lead sponsor: First Affiliated Hospital of Zhejiang University
Sponsor class: OTHER
First posted: 2019-08-16
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: This is a single-center, open, single-arm, exploratory phase Ib trial
Primary purpose: TREATMENT

Brief summary: To assess the safety and efficacy of third-line and above therapy of patients with local advanced or metastatic non-small cell lung cancer (NSCLC) with combined treatment with launched recombinant humanized anti-PD-1 monoclonal antibody and Donafenib Tosilate

Detailed description: Donafenib has a multi-target and dual anti-tumor effect, similar to sorafenib toluene sulfonate, and its effect is similar to that of sorafenib toluene sulfonate. Donafenib has the potential to be effective in the treatment of cancer, including advanced non-small cell lung cancer. PD-1 inhibitor has become a new therapy for advanced non-small cell lung cancer because of its strong specificity, definite efficacy, small side effects and long time of tumor control.

This is a single-center, open, single-arm, exploratory phase Ib trial. There were two dosages of donafenib (100mg qd and 100mg bid, respectively). Three to six subjects were enrolled in the dosages of 100mg qd. The investigators determined that the dosages of 100mg bid were well tolerated

Eligibility criteria: Inclusion Criteria:

1、18 years age or older ,male or female

2、Histologically or cytologically confirmed diagnosis of local advanced or metastatic NSCLC

3、Previously received with two or more systemic Antitumor treatments (Chemotherapy or targeted therapy). Chemotherapy treatments must include a two-drug regimen containing platinum, patients with EGFR TKI drug resistance and unknow T790M mutation, after AZD9291 treatment patients with T790M mutation could be enrolled

4、At least one measurable lesion as defined by RECIST 1.1. A previously irradiated site lesion may only be counted as a target lesion if there is clear sign of progression since the irradiation

5、Asymptomatic patients with uncontrolled brain metastases or brain metastases involving the pia mater

6、Patients must have recovered from all toxicities related to prior anticancer therapies to ≤ 2 (CTCAE v5.0). AE of Neurology must be ≤ 1

7、Life expectancy ≥ 12 weeks

8、ECOG performance status 0-1

Exclusion Criteria:

1. Small cell lung cancer (including small lung cancer mixed with non-small cell lung cancer)
2. Patients at risk of bleeding treated with antiangiogenic drugs
3. Subjects who are using immunosuppressive agents, or systemic, or absorbable topical hormone therapy for immunosuppressive purposes (dose \>10mg/ dprednisone or other therapeutic hormones) and who continue to use it for 2 weeks prior to enrollment
4. Patients with active, known or suspected autoimmune diseases, including tuberculosis, HIV infection, active hepatitis, etc.
5. Patients with previous and current objective evidence of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radioactive pneumonia, drug-related pneumonia, severe impairment of lung function, etc
6. Women who are pregnant or lactating, or who are unwilling to use contraception during the trial

Primary outcomes:
measure: safety assessments
timeFrame: From signing ICF to 30 days after the end of treatment
Secondary outcomes:
measure: Effective evaluation
timeFrame: Continue treatment until the end of treatment，an average of 12 months
measure: Overall response rate
timeFrame: Continue treatment until the end of treatment，an average of 12 months
measure: Disease control rate
timeFrame: Continue treatment until the end of treatment，an average of 12 months
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The First Affiliated Hospital of College of Medicine Zhejiang University
state: Zhejiang
Study officials:
affiliation: First Affiliated Hospital of Zhejiang University
name: Jianying Zhou, MD
role: PRINCIPAL_INVESTIGATOR
References: