Platinum-Based Chemotherapy Plus Ramucirumab in Patients With Advanced NSCLC Who Have Progressed on First Line Anti-PD-1 Immunotherapy

NCT03904108 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: IRB2019-00094
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

This is a non-randomized, phase-II study of platinum doublet chemotherapy plus ramucirumab in patients with advanced NSCLC who have progressed on first line anti-PD-1 Immunotherapy. Up to 25 evaluable participants will be enrolled over a period of 2 years. Seven patients will be recruited at the first stage .Eligible patients would include those treated with a PD-1 inhibitor as primary therapy and exhibit evidence of disease progression, but maintain a good performance status. The investigators hypothesize that immune therapy acts as chemo-sensitizer and patients treated with standard platinum-based combination chemotherapy with the addition of the anti-angiogenic agent Ramucirumab, after immunotherapy will have higher response rates

Conditions

Carcinoma, Non-Small-Cell Lung

Keywords

NSCLC; Immunotherapy; Ramucirumab; anti-PD-1

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Objective Response Per RECIST 1.1 as Assessed by Central Imaging

  Objective response (OR) is the occurrence of CR or PR as the best overall response. OR will be based on responses confirmed using the subsequent 6-weekly scan. OR is based on the Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

  ≥18 weeks, up to maximum of 12 months

• Number of Participants With Treatment Related Dose Delay or Treatment Discontinuation

  Adverse events will be recorded in relation to each cycle of treatment and graded according to CTCAE criteria. The toxicity co-primary outcome measure for the trial is defined as the occurrence of a treatment-related dose delay or treatment discontinuation due to toxicity

  Through study completion, up to a maximum of 12 months. Serious AEs: Up to 90 days after last dose of study treatment, Other AEs: Up to 30 days after last dose of study treatment

Study Arms (1)

Ramucirumab

EXPERIMENTAL

Ramucirumab 10 mg/kg IV day 1, every 3 weeks for 4 cycles

Drug: Ramucirumab

Interventions

Ramucirumab DRUG

platinum doublets chemotherapy plus ramucirumab, intravenously(IV)

Also known as: cyramza, BLA 125477

Ramucirumab

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed stage IV NSCLC per 8th IASCL (International Association for the Study of Lung Cancer) of squamous and non-squamous histology, with progression on first line anti-PD1 immunotherapy.
• Oligo-metastatic stage IV patients who received concurrent chemotherapy with thoracic radiation, followed by durvalumab consolidation and had progression of disease.
• Locally advanced un-resectable NSCLC patients who received concurrent chemotherapy with thoracic radiation, followed by durvalumab consolidation and had progression of disease.
• Males or females at least 18 years of age.
• ECOG (Eastern Cooperative Oncology Group) performance status of 0 or 1.
• Measureable disease by CT or MRI per RECIST 1.1 criteria.
• Life expectancy of at least 3 months.
• Resolution of all clinically significant toxic effects of prior anticancer therapy to Grade ≤1 by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.0.
• The participant must have adequate organ function, defined as:
• Total bilirubin less than or equal to the upper limit of normal value (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x ULN, or ≤5 x ULN if the transferase elevation was due to liver metastases.
• Serum creatinine ≤1.5 x ULN or calculated creatinine clearance ≥50 mL/min (per the Cockcroft-Gault formula or equivalent and/or 24-hour urine collection \[Cockcroft-Gault glomerular filtration rate = (140-age) \* (Wt in kg) \* (0.85 if female) / (72 \* Cr) where "Cr" is serum creatinine\]).
• Absolute neutrophil count (ANC) ≥1.5 x 103/μL (≥1.5 x 109/L), hemoglobin ≥10.0 g/dL (≥ 6.2 mmol/L), and platelets ≥100 x 103/μL (≥100 x 109/L).
• International Normalized Ratio (INR) less than or equal to 1.5, or prothrombin time and partial thromboplastin time less than or equal to 1.5 x ULN.
• The participant does not have cirrhosis at a level of Child-Pugh B (or worse) or cirrhosis (any degree) and a history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis. Clinically meaningful ascites is defined as ascites resulting from cirrhosis and requiring ongoing treatment with diuretics and/or paracentesis.
• Urinary protein is ≤1+ on dipstick or routine urinalysis (UA). If urine dipstick or routine analysis indicated proteinuria ≥2+, then a 24-hour urine must be collected and must demonstrate \<1000 mg of protein in 24 hours to allow participation in the study.

You may not qualify if:

• Participant has received prior cytotoxic therapy or targeted oral agents for the treatment of their stage IV NSCLC. Participants with oligo-metastatic stage IV disease who received concurrent chemotherapy with thoracic radiation, followed by durvalumab consolidation with disease progression were eligible.
• Participant has an EGFR (epidermal growth factor receptor) sensitizing mutation, ALK translocation and/or an ROS-1 gene rearrangement.
• Participant has undergone major surgery within 28 days prior to screening, or subcutaneous venous access device placement within 7 days prior to screening. Furthermore, any partcipant with postoperative bleeding complications or wound complications from a surgical procedure performed in the last 2 months will be excluded.
• Participant has untreated CNS (central nervous system) metastases. Participants with treated brain metastases were eligible if they were clinically stable with regard to neurologic function, off steroids after cranial irradiation (whole brain radiation therapy, focal radiation therapy, and stereotactic radiosurgery) ending at least 2 weeks prior to screening, or after surgical resection performed at least 28 days prior to screening. No evidence of Grade ≥1 CNS hemorrhage based on pretreatment MRI or IV contrast CT scan (performed within 21 days before screening).
• There is radiologically documented evidence of major blood vessel invasion or encasement by cancer.
• There is radiographic evidence of intra-tumor cavitation, regardless of tumor histology.
• Participant has a history of uncontrolled hereditary or acquired thrombotic disorder.
• Participant has a history of gross hemoptysis (defined as bright red blood or ≥1/2 teaspoon) within 2months prior to screening.
• Participant has clinically relevant congestive heart failure (CHF; NYHA II-IV) or symptomatic or poorly controlled cardiac arrhythmia.
• Participant has experienced any arterial thrombotic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, within 6 months prior to screening.
• Participant has uncontrolled arterial hypertension ≥150 / ≥90 mm Hg despite standard medical management.
• Participant has a serious or non-healing wound, ulcer, or bone fracture within 28 days prior to screening.
• Participant has significant bleeding disorders, vasculitis, or experienced Grade 3-4 gastrointestinal (GI) bleeding within 3 months prior to screening.
• History of GI perforation and/or fistulae within 6 months prior to screening.
• Participant has bowel obstruction,history or presence of inflammatory enteropathy or extensive intestinal resection (hemicolectomy or extensive small intestine resection with chronic diarrhea), Crohn's disease, ulcerative colitis, or chronic diarrhea.

Sponsors & Collaborators

• ROGER S KERESZTES MD: lead

Study Sites (1)

Stony Brook University

Stony Brook, New York, 11794, United States

Location

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MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Ramucirumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. Roger Keresztes
• Organization: Stony Brook University

roger.keresztes@stonybrookmedicine.edu

631-638-1000

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Associate Professor

Study Record Dates

• First Submitted: April 2, 2019
• First Posted: April 4, 2019
• Study Start: June 27, 2019
• Primary Completion: July 27, 2020
• Study Completion: July 27, 2020
• Last Updated: May 26, 2022
• Results First Posted: May 26, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)