Trial Title:
A Study of Lorlatinib in Combination With Ramucirumab in People With Lung Cancer
NCT ID:
NCT06007937
Condition:
Non Small Cell Lung Cancer
Metastatic
Recurrent
Conditions: Official terms:
Lung Neoplasms
Ramucirumab
Conditions: Keywords:
Lorlatinib
Ramucirumab
23-131
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Lorlatinib
Description:
Lorlatinib 100 mg orally daily
Arm group label:
Lorlatinib and ramucirumab
Intervention type:
Drug
Intervention name:
Ramucirumab
Description:
Ramucirumab 10 mg/kg intravenous infusion once every three weeks is a tolerable and safe
dose.
Arm group label:
Lorlatinib and ramucirumab
Summary:
This study will test the safety of the combination of ramucirumab and lorlatinib. The
researchers will test one or two different doses of lorlatinib in combination with
ramucirumab to find the drug combination dose that causes few or mild side effects in
participants. Once the researchers find this dose, they can test it in future
participants to see if it is effective in treating their metastatic ALK-rearranged NSCLC.
The researchers are also looking to see whether there are specific genes or DNA sequences
associated with a response to treatment with lorlatinib and ramucirumab.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Written informed consent
- Age >18 years old
- Metastatic or recurrent, biopsy-proven non-small cell lung cancer
- ALK fusion identified by next generation sequencing (NGS) or IHC on material
obtained from tumor or plasma
- Measurable (RECIST 1.1) indicator lesion not previously irradiated
- Karnofsky performance status (KPS) ≥ 70%
- Adequate organ function defined as follows: ANC ≥1.5 × 10^9 /L, platelets ≥100 ×
10^9/L, hemoglobin ≥ 9 g/dL, INR ≤ 1.5, PTT or aPTT <1.5x ULN, total bilirubin ≤ 1.5
× ULN (Patients with Gilbert's syndrome with a total bilirubin ≤2.0 times ULN and
direct bilirubin within normal limits are permitted), AST ≤ 3 × ULN, ALT ≤ 3 × ULN
or ≤ 5 x ULN in the setting of liver metastases, Cr ≤1.5 ULN or CrCl ≥ 40 mL/min. If
Cr is
≥ 1.5x ULN, a 24-hr urine collection to calculate creatinine clearance must be
performed
°The patient's urinary protein is ≤1+ on dipstick or routine urinalysis (UA); if
urine dipstick or routine analysis is ≥2+, a 24-hour urine collection for protein
must demonstrate <1000 mg of protein in 24 hours to allow participation in this
protocol).
- Patients on full-dose anticoagulation must be on a stable dose of oral anticoagulant
or low molecular weight heparin for a minimum of 14 days prior to trial enrollment
without signs of active bleeding or pathological condition that carries a high risk
of bleeding (eg, tumor invading major vessels or known varices). Patients on
warfarin must have an INR ≤ 3.0
- Patients must have recovered (Common Terminology Criteria for Adverse Events [CTCAE]
version 5 Grade ≤1) from the acute effects of prior therapy, except for residual
alopecia or peripheral neuropathy (up to grade 2 allowed)prior to start of therapy
- Patients in cohort 1 will be treatment-naïve in the metastatic setting. Prior
treatment with adjuvant chemotherapy is allowed
- Patients in cohort 2 will have progressed or be intolerant of at least one second
generation ALK TKI, including alectinib, brigatinib, or ceritinib.
- Patients may have received multiple ALK TKIs as well as chemotherapy, but one of
these treatments must have been with a second-generation ALK TKI.
- Because the teratogenicity of ramucirumab is not known, the patient, if sexually
active, must be postmenopausal, surgically sterile, or using effective contraception
(hormonal or barrier methods).
- Female patients of childbearing potential must have a negative serum pregnancy test
within 7 days prior to first dose of protocol therapy.
Exclusion Criteria:
- Prior lorlatinib or ramucirumab exposure
- Symptomatic, unstable brain metastasis requiring therapy with steroids or radiation
therapy. Patients with clinically stable brain metastases (previously treated or
untreated) are eligible
- Women who are breastfeeding or pregnant
- Major radiotherapy within 2 weeks of starting treatment on protocol
- Major surgery within 4 weeks of starting treatment on protocol or minor
surgery/subcutaneous venous access device placement within 7 days prior to the first
dose of protocol therapy
- Less than 3 weeks since previous chemotherapy, 4 weeks since immunotherapy, and 2
weeks from any investigational therapy
- Significant bleeding disorders or grade ≥3 bleeding episode within 12 weeks prior to
enrollment. Patients with history of gross hemoptysis (defined as bright red blood
of ≥1/2 teaspoon) within 8 weeks prior to enrollment will be excluded
- New or history of diagnosis of deep vein thrombosis (DVT) or pulmonary embolism (PE)
or other significant thromboembolic event in the 12 weeks prior to first dose of
protocol therapy. Patients with thromboembolic events diagnosed >12 weeks prior to
protocol therapy are eligible if on stable doses of anticoagulation as outlined
above. Venous port or catheter thrombosis or superficial venous thrombosis are not
considered significant events
- GI perforation and/or fistula or bowel obstruction within 6 months or risk factors
for perforation prior to enrollment
- Child-Pugh B or greater cirrhosis or cirrhosis (any degree) and a history of hepatic
encephalopathy or clinically meaningful ascites resulting from cirrhosis. Clinically
meaningful ascites is defined as ascites from cirrhosis requiring diuretics or
paracentesis
- Uncontrolled hypertension, defined as systolic BP ≥160 mm Hg or diastolic BP ≥100 mm
Hg, prior to initiating study treatment, despite hypertensive intervention
- Serious or non-healing wound, ulcer or bone fracture within 28 days of enrollment
- Radiologically documented evidence of major blood vessel invasion or encasement by
cancer or radiographic evidence of intratumor cavitation
- Active systemic bacterial infection (requiring intravenous [IV] antibiotics at time
of initiating study treatment), fungal infection, or detectable viral infection
(such as known human immunodeficiency virus positivity with known active hepatitis B
or C [for example, hepatitis B surface antigen positive]. Screening is not required
for enrollment.
- Arterial thrombotic event or arterial thromboembolic event, including myocardial
infarction, unstable angina, congestive heart failure ≥ NYHA class III,
cerebrovascular accident or transient ischemic attack, within 6 months prior to
enrollment
- Planned elective or major surgery during the trial
- Chronic therapy with any of the following within 7 days of enrollment:
- Antiplatelet agents (such as clopidogrel, ticlopidine, dipyridamole, or
anagrelide)
- Aspirin up to 325 mg/day is permitted
- Serious uncontrolled medical disorders or psychological conditions that would, in
the opinion of the investigator, limit the patient's ability to complete the study
or sign an informed consent document
- Patients with unavoidable strong CYP3A inducer or inhibitor use (see table 15.4 for
list of agents)
Gender:
All
Minimum age:
19 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Memorial Sloan Kettering Monmouth (All Protocol Activities)
Address:
City:
Middletown
Zip:
07748
Country:
United States
Status:
Recruiting
Contact:
Last name:
Gregory Riely, MD, PhD
Phone:
646-608-3913
Facility:
Name:
Memorial Sloan Kettering Bergen (All Protocol Activities)
Address:
City:
Montvale
Zip:
07645
Country:
United States
Status:
Recruiting
Contact:
Last name:
Gregory Riely, MD, PhD
Phone:
646-608-3913
Facility:
Name:
Memorial Sloan Kettering Cancer Center Suffolk - Commack (All Protocol Activities)
Address:
City:
Commack
Zip:
11725
Country:
United States
Status:
Recruiting
Contact:
Last name:
Gregory Riely, MD, PhD
Phone:
646-608-3913
Facility:
Name:
Memorial Sloan Kettering West Harrison (All Protocol Activities)
Address:
City:
Harrison
Zip:
10604
Country:
United States
Status:
Recruiting
Contact:
Last name:
Gregory Riely, MD, PhD
Phone:
646-608-3913
Facility:
Name:
Memorial Sloan Kettering Cancer Center (All Protocol Activities)
Address:
City:
New York
Zip:
10065
Country:
United States
Status:
Recruiting
Contact:
Last name:
Gregory Riely, MD, PhD
Phone:
646-608-3913
Contact backup:
Last name:
Alexander Drilon, MD
Phone:
646-608-3758
Investigator:
Last name:
Gregory Riely, MD, PhD
Email:
Principal Investigator
Facility:
Name:
Memorial Sloan Kettering Nassau (All Protocol Activities)
Address:
City:
Rockville Centre
Zip:
11570
Country:
United States
Status:
Recruiting
Contact:
Last name:
Gregory Riely, MD, PhD
Phone:
646-608-3913
Start date:
August 17, 2023
Completion date:
August 17, 2028
Lead sponsor:
Agency:
Memorial Sloan Kettering Cancer Center
Agency class:
Other
Collaborator:
Agency:
Eli Lilly and Company
Agency class:
Industry
Source:
Memorial Sloan Kettering Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06007937
http://www.mskcc.org/mskcc/html/44.cfm
