A Phase 2 Study of Ramucirumab in Combination with Weekly Docetaxel in Patients with Lung Cancer Following Disease Progression after Prior Platinum-based Chemotherapy
- Conditions
- Stage IV non-small cell lung cancer (NSCLC)MedDRA version: 19.0Level: LLTClassification code 10025048Term: Lung cancer non-small cell recurrentSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-001317-25-ES
- Lead Sponsor
- illy S.A.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 50
- Patients who have had disease progression from prior platinum-based chemotherapy regimen for locally advanced or metastatic NSCLC.
- Prior immunotherapy for NSCLC is allowed.
- Age of at least 18 years at the time of signing informed consent.
- The patient has an Eastern Cooperative Oncology Group performance status of 0 or 1.
- The patient has histologically or cytologically confirmed NSCLC.
- The patient has metastatic NSCLC disease (Stage IV) at the time of first dose of study treatment.
-Patients have measurable disease at the time of first dose of study treatment documented by computed tomography (CT) scan or magnetic resonance imaging (MRI).
- The patient has resolution to Grade =1 by NCI-CTCAE, Version 4.0, of all clinically significant toxic effects of prior locoregional therapy, surgery, or other anticancer therapy.
- The patient has adequate organ function
- The patient’s urinary protein is <2+ on dipstick or routine urinalysis (UA). If urine dipstick or routine analysis indicates proteinuria =2+, then a 24-hour urine must be collected and must demonstrate <2 g of protein in 24 hours to allow participation in the study.
- For male patients, are sterile (including vasectomy confirmed by post vasectomy semen analysis) or agree to use a highly effective method of contraception (2 methods preferred, or per country requirements, whichever is more strict), and to not donate sperm starting with the first dose of study treatment, during the study, and for at least 6 months following the last dose of study treatment or country requirements, whichever is longer.
- For female patients, are surgically sterile, postmenopausal, or agree to use a highly effective method of contraception (2 methods preferred, or per country requirements, whichever is more strict) during the study and for 6 months following the last dose of study treatment or country requirements, whichever is longer.
- Female patients of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to first dose of study treatment.
- The patient has a life expectancy of =3 months.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30
- Prior therapy with docetaxel or ramucirumab.
- The patient has received more than 1 prior chemotherapy regimen for locally advanced or metastatic NSCLC; however, prior maintenance chemotherapy for locally advanced or metastatic NSCLC is allowed.
- The patient's tumour contains small cell lung cancer.
- The patient has undergone major surgery within 28 days prior to first dose of study treatment, or subcutaneous venous access device placement within 7 days prior to first dose of study treatment. Furthermore, any patient with postoperative bleeding complications or wound complications from a surgical procedure performed in the last 2 months will be excluded.
- The patient has a 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.
- The patient has peripheral neuropathy Grade =2 (NCI-CTCAE v 4.0).
- The patient has an elective or a planned major surgery during the course of the trial.
- The patient is receiving concurrent treatment with other anticancer therapy, including other chemotherapy, immunotherapy, hormonal therapy, chemoembolization, or targeted therapy.
- The patient has symptomatic, active, or untreated central nervous system (CNS) metastases. Brain metastases that are asymptomatic, stable and not requiring steroid use, and previously treated by radiation are allowed (refer to Exclusion Criterion [19]). The patient may have no evidence of Grade =1 CNS hemorrhage based on pretreatment MRI or I.V. contrast CT scan (performed within 21 days before first dose of study treatment).
- The patient has radiologically documented evidence of major blood vessel invasion or encasement by cancer.
- The patient has radiographic evidence of intratumor cavitation, regardless of tumor histology.
- The patient has a history of uncontrolled hereditary or acquired thrombotic disorder.
- The patient is receiving chronic therapy with nonsteroidal anti-inflammatory drugs (NSAIDs; for example, indomethacin, ibuprofen, naproxen, or similar agents) or other antiplatelet agents (for example, clopidogrel, ticlopidine, dipyridamole, and anagrelide). Aspirin use at doses up to 325 mg/day is permitted.
- Patients with a history of gross hemoptysis (defined as bright red blood or =1/2 teaspoon) within 2 months prior to first dose of study treatment.
- The patient has clinically relevant congestive heart failure (New York Heart Association Class II-IV) or symptomatic or poorly controlled cardiac arrhythmia.
- The patient has experienced any arterial thrombotic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, within 6 months prior to first dose of study treatment.
- The patient has uncontrolled arterial hypertension =150 / =90 mm Hg despite standard medical management.
- The patient has had a serious or nonhealing wound, ulcer, or bone fracture =28 days prior to first dose of study treatment.
- The patient has significant bleeding disorders, vasculitis, or experienced Grade 3-4 gastrointestinal (GI) bleeding within 3 months prior to first dose of study treatment.
- History of GI perforation and / or fistulae within 6 months prior to first dose of study treatment.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess safety, as measured by the rate of Grade =3 neutropenia, of ramucirumab in combination with weekly docetaxel in all patients;Secondary Objective: - To assess safety, as measured by the rate of febrile neutropenia, of ramucirumab in combination with weekly docetaxel in all patients<br>- To assess efficacy of ramucirumab in combination with weekly docetaxel in all patients<br>- To assess safety and efficacy of ramucirumab in combination with weekly docetaxel in patients who have received prior immunotherapy for NSCLC and in patients who have not received prior immunotherapy for NSCLC<br>- To assess the PK of ramucirumab;Primary end point(s): Safety: Grade =3 neutropenia;Timepoint(s) of evaluation of this end point: Grade =3 neutropenia will be assessed at the Primary Analysis when there are at least 31 patients who have completed at least 12 weeks of study treatment or have had progressive disease, or discontinued study treatment due to toxicity.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): - Safety (include but are not limited to): febrile neutropenia, TEAEs, SAEs, and deaths<br>- ORR per RECIST 1.1<br>- PFS<br>- OS<br>- Minimum serum concentration of ramucirumab;Timepoint(s) of evaluation of this end point: The secondary endpoints will be assessed at the final analysis when at least 50 patients have completed at least 12 weeks of study treatment or have had progressive disease, or discontinued study treatment due to toxicity.