Trial Title:
A Pilot Phase II Study of Maintenance Cabozantinib Plus Pembrolizumab for Patients With Metastatic Squamous Non-Small Cell Lung Cancer (sqNSCLC)
NCT ID:
NCT05613413
Condition:
Metastatic Squamous Non-Small Cell Lung Carcinoma
Conditions: Official terms:
Carcinoma, Non-Small-Cell Lung
Pembrolizumab
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Cabozantinib 40 MG
Description:
Cabozantinib is taken my mouth
Arm group label:
Single
Intervention type:
Drug
Intervention name:
Pembrolizumab 200mg
Description:
Pembrolizumab is given intravenously
Arm group label:
Single
Intervention type:
Drug
Intervention name:
Pembrolizumab 400mg
Description:
Pembrolizumab is given intravenously
Arm group label:
Single
Summary:
This is a phase II study to assess the efficacy, safety, and Health Related Quality of
Life (HRQoL) of combination cabozantinib and pembrolizumab as maintenance therapy for
patients with metastatic squamous Non Small Cell Lung Cancer(sqNSCLC) who have received 4
cycles of induction therapy with pembrolizumab, carboplatin, and nab-paclitaxel or
paclitaxel
Detailed description:
This is a phase II study to assess the efficacy, safety, and Health Related Quality of
Life (HRQoL) of combination cabozantinib and pembrolizumab as maintenance therapy for
patients with metastatic sqNSCLC who have received 4 cycles of induction therapy with
pembrolizumab, carboplatin, and nab-paclitaxel or paclitaxel and achieved disease control
following induction therapy defined as complete response, partial response, or stable
disease per Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1 criteria.
Subjects with disease control would proceed to maintenance therapy with pembrolizumab and
cabozantinib.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Written informed consent and HIPAA authorization for release of personal health
information prior to registration. NOTE: HIPAA authorization may be included in the
informed consent or obtained separately.
2. Age ≥ 18 years at the time of consent.
3. ECOG Performance Status of 0, 1, or 2 within 28 days prior to registration
4. Life expectancy of 6 months or greater as determined by the site investigator.
5. Subjects with histologically or cytologically confirmed squamous non-small cell lung
cancer (sqNSCLC).
6. Subjects with stage IV NSCLC as defined by American Joint Committee on Cancer (AJCC)
8th Edition who have not received prior therapy for stage IV NSCLC. Patients with
locally advanced or recurrent disease who are candidates for first-line induction
systemic therapies for stage IV NSCLC are also allowed.
• Only patients with disease control, defined as complete response (CR), partial
response (PR), or stable disease (SD) to induction therapy will be allowed to
receive maintenance cabozantinib plus pembrolizumab arm of trial. Patients who have
progression of disease (POD) following induction therapy will proceed to second-line
therapy of local clinician's choice. Only those patients who proceed to maintenance
cabozantinib and pembrolizumab therapy will be evaluable for primary and secondary
objectives.
7. Subjects whose tumors have been tested for PD-L1 expression.
8. Demonstrate adequate organ function as defined below. All screening labs to be
obtained within 14 days prior to registration.
System Laboratory Value Hematological. White blood cell (WBC) ≥ 2.5K/uL Absolute
Neutrophil Count (ANC) ≥ 1,500/uL without the support of Filgrastim or ≥ 1,000/L in
subjects with constitutional neutropenia Hemoglobin (Hgb) ≥ 9 g/dL Platelets (Plt) ≥
100,000/µL without transfusion. Renal Serum creatinine Calculated creatinine
clearance1 ≤ 1.5 mg/dL
≥ 40 mL/min; for subjects with serum creatinine > 1.5 mg/dL Urine protein/creatinine
ratio (UPCR) ≤ 1 mg/mg (≤ 113.2 mg/mmol), or 24-h urine protein ≤ 1 g Hepatic Total
Bilirubin2 OR Direct Bilirubin ≤ 1.5 × upper limit of normal (ULN) or ≤ 3 × ULN for
subjects with Gilbert's disease
≤ ULN for subjects with total bilirubin levels > 1.5 x ULN Aspartate
aminotransferase (AST) ≤ 3 × ULN or ≤ 5 x ULN for subjects with known hepatic
metastasis Alanine aminotransferase (ALT) ≤ 3 × ULN or ≤ 5 x ULN for subjects with
known hepatic metastasis Alkaline phosphatase (ALP) ≤ 3 × ULN or ≤ 5 x ULN with
documented bone metastases.
Serum albumin ≥ 2.8 g/dl Coagulation International Normalized Ratio (INR)
- 1.3 × ULN; For subjects receiving warfarin or LMWH, the subjects must, in the
site investigator's opinion, be clinically stable with no evidence of active
bleeding while receiving anticoagulant therapy. The INR for these subjects may
exceed 1.3 × ULN if that is the goal of anticoagulant therapy.
1 Cockcroft-Gault formula will be used to calculate creatinine clearance (See
SPM) 2 Except in patients with Gilbert's syndrome who must have a total
bilirubin less than 3.0 mg/dl.
9. Recovery to baseline or ≤ Grade 1 CTCAE v5.0 from toxicities related to any prior
treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive
therapy.
10. Sexually active fertile subjects and their partners must agree to use medically
accepted methods of contraception (e.g., barrier methods, including male condom,
female condom, or diaphragm with spermicidal gel) during the course of the study and
for 4 months after the last dose of cabozantinib and 4 months after the last dose of
pembrolizumab.
11. Females of childbearing potential must have a negative serum pregnancy test within 3
days prior to registration. Female subjects of childbearing potential must not be
pregnant at screening. Female subjects are considered to be of childbearing
potential unless one of the following criteria is met: documented permanent
sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or
documented postmenopausal status (defined as 12 months of amenorrhea in a woman > 45
years-of-age in the absence of other biological or physiological causes. In
addition, females < 55 years-of-age must have a serum follicle stimulating (FSH)
level > 40 mIU/mL to confirm menopause). Note: Documentation may include review of
medical records, medical examinations, or medical history interview by study site.
12. As determined by the enrolling physician or protocol designee, subjects should be
capable of understanding and complying with the protocol requirements and must have
signed the informed consent document.
13. Willingness and ability to comply with scheduled visits, treatment plans, laboratory
tests, and other study procedures.
Exclusion Criteria:
1. Active infection requiring systemic therapy.
2. Pregnant or breastfeeding. NOTE: breast milk cannot be stored for future use while
the mother is being treated on study.
3. Prior treatment with cabozantinib.
4. Receipt of any type of small molecule kinase inhibitor (including investigational
kinase inhibitor) within 2 weeks before first dose of study treatment.
5. Receipt of any type of cytotoxic, biologic or other systemic anticancer therapy
(including investigational) within 4 weeks before first dose of study treatment.
6. Radiation therapy for bone metastasis within 2 weeks or any other radiation therapy
within 4 weeks before first dose of study treatment. Systemic treatment with
radionuclides within 6 weeks before first dose of study treatment. Subjects with
clinically relevant ongoing complications from prior radiation therapy are not
eligible.
7. Radiologically documented evidence of major blood vessel invasion or encasement by
cancer.
8. Radiographic evidence of central cavitating pulmonary lesion(s) or known
endotracheal or endobronchial disease manifestation. Patients with peripheral
cavitary lesions prior to induction therapy may be enrolled but will only be allowed
to continue maintenance therapy on trial if they have disease control and resolution
of cavitation after induction therapy. The development of cavitation recurrence or
new intra-thoracic cavitations during maintenance therapy will require Cabozantinib
to be stopped during maintenance therapy.
9. Patients with targetable genomic aberrations for which FDA-approved targeted therapy
is available (e.g. ROS1, MET exon 14 skipping mutations, BRAFV600E, ALK, EGFR, ALK,
RET, and NTRK fusions).
10. The subject has uncontrolled, significant intercurrent or recent illness including,
but not limited to, the following conditions:
1. Cardiovascular disorders:
i. Congestive heart failure New York Heart Association Class 3 or 4, unstable angina
pectoris, serious cardiac arrhythmias.
ii. Uncontrolled hypertension defined as sustained blood pressure (BP) > 140 mm Hg
systolic or > 90 mm Hg diastolic despite optimal antihypertensive treatment.
iii. Stroke (including transient ischemic attack [TIA]), myocardial infarction (MI), or
other ischemic event, or thromboembolic event (e.g., deep venous thrombosis, pulmonary
embolism) within 6 months before first dose of study treatment.
iv. Subjects with a diagnosis of incidental, subsegmental PE or DVT within 6 months are
allowed if stable, asymptomatic, and treated with a stable dose of permitted
anticoagulation for at least 1 week before first dose of study treatment.
b. Gastrointestinal (GI) disorders including those associated with a high risk of
perforation or fistula formation: i. The subject has evidence of tumor invading the GI
tract, active peptic ulcer disease, inflammatory bowel disease (e.g., Crohn's disease),
diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute
pancreatitis, acute obstruction of the pancreatic duct or common bile duct, or gastric
outlet obstruction.
ii. Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess
within 6 months before first dose of study treatment. Note: Complete healing of an
intra-abdominal abscess must be confirmed before first dose of study treatment.
c. Other clinically significant disorders that would preclude safe study participation.
i. Serious non-healing wound/ulcer/bone fracture. ii. Malabsorption syndrome. iii.
Uncompensated/symptomatic hypothyroidism. iv. Moderate to severe hepatic impairment
(Child-Pugh B or C). v. Requirement for hemodialysis or peritoneal dialysis. vi. Any
condition requiring systemic treatment with either steroid therapy (>10 mg daily
prednisone equivalent) or any other form of immunosuppressive therapy within 2 weeks
prior to first dose of study treatment.
1. Note: Inhaled, intranasal, intra-articular, or topical steroids are permitted.
Adrenal replacement steroid doses > 10 mg daily prednisone equivalent are permitted.
Transient short-term use of systemic corticosteroids for allergic conditions (e.g.,
contrast allergy) is also allowed.
10. Clinically significant hematuria, hematemesis, or hemoptysis of > 0.5 teaspoon (2.5
ml) of red blood, or other history of significant bleeding (e.g., pulmonary
hemorrhage) within 12 weeks before first dose of study treatment.
11. Known brain metastases or cranial epidural disease unless adequately treated with
radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks
prior to first dose of study treatment after radiotherapy or at least 4 weeks prior
to first dose of study treatment after major surgery (e.g., removal or biopsy of
brain metastasis). Subjects must have complete wound healing from major surgery or
minor surgery before first dose of study treatment. Eligible subjects must be
neurologically asymptomatic and without corticosteroid treatment at the time of
first dose of study treatment.
12. Concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin
inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet
inhibitors (e.g., clopidogrel). Allowed anticoagulants are the following:
1. Prophylactic use of low-dose aspirin for cardio-protection (per local applicable
guidelines) and low-dose low molecular weight heparins (LMWH).
2. Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors
rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who
are on a stable dose of the anticoagulant for at least 1 week before first dose of
study treatment without clinically significant hemorrhagic complications from the
anticoagulation regimen or the tumor.
13. Administration of a live, attenuated vaccine within 30 days before first dose
of study treatment.
14. The subject has uncontrolled, significant intercurrent or recent illness,
including, but not limited to, an active or history of autoimmune disease or
immune deficiency; idiopathic pulmonary fibrosis, organizing pneumonia,
pneumonitis; active infection requiring systemic treatment, infection with
human immunodeficiency virus (HIV), AIDS-related illness, acute or chronic
hepatitis B or C infection, positive test for tuberculosis, moderate to severe
hepatic impairment (Child-Pugh B or C).
15. Previously identified allergy or hypersensitivity to components of the study
treatment formulations or history of severe infusion-related reactions to
monoclonal antibodies. Subjects with rare hereditary problems of galactose
intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption are
also excluded.
16. Any other active malignancy at time of first dose of study treatment or
diagnosis of another malignancy within 3 years prior to first dose of study
treatment that requires active treatment, except for locally curable cancers
that have been apparently cured, such as basal or squamous cell skin cancer,
superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or
breast.
17. Major surgery (e.g., laparoscopic nephrectomy, GI surgery, removal or biopsy of
brain metastasis) within 2 weeks before first dose of study treatment. Minor
surgeries within 10 days before first dose of study treatment. Subjects must
have complete wound healing from major surgery or minor surgery before first
dose of study treatment. Subjects with clinically relevant ongoing
complications from prior surgery are not eligible.
a. NOTE: Hepatic biliary stent placement, PleurX catheter, port placement, ureteral stent
or other minor surgeries are allowed. NOTE: Subject must have adequately recovered from
the toxicity and/or complications of major surgery prior to study registration, as
determined by the treating physician.
18. Previously received a solid organ transplant or allogeneic progenitor/stem cell
transplant.
19. Previous exposure or known allergy to cabozantinib or any of its excipients.
20. Inability to swallow tablets or unwillingness or inability to receive IV
administration.
21. Corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms per
electrocardiogram (ECG) within 14 days before first dose of study treatment.
Furthermore, subjects with a history of additional risk factors for torsades de
pointes (e.g., long QT syndrome) are also excluded [add reference for Fridericia
formula].
a. Note: If a single ECG shows a QTcF with an absolute value > 500 ms, two additional
ECGs at intervals of approximately 3 min must be performed within 30 min after the
initial ECG, and the average of these three consecutive results for QTcF will be used to
determine eligibility.
22. Other severe acute or chronic medical or psychiatric condition or laboratory
abnormality that may increase the risk associated with study participation or
investigational product administration, interfere with protocol compliance, or may
interfere with the interpretation of study results and, in the judgment of the
investigator, would make the subject inappropriate for enrollment in this study.
23. Any mental or medical condition that prevents the subject from giving informed
consent or participating in the trial.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Ryan Nguyen
Address:
City:
Chicago
Zip:
60612
Country:
United States
Status:
Recruiting
Contact:
Last name:
Ryan Nguyen, DO
Phone:
312-996-1581
Email:
rnguye8@uic.edu
Contact backup:
Last name:
Arielle Guzman, MPH
Phone:
312-355-8838
Email:
abguzma2@uic.edu
Start date:
December 28, 2022
Completion date:
September 2028
Lead sponsor:
Agency:
University of Illinois at Chicago
Agency class:
Other
Source:
University of Illinois at Chicago
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05613413
