Cabozantinib and temozolomide in patients with advanced progressive neuroendocrine tumors: a phase 2 study.
Mauro Cives, Giuseppina Della Vittoria Scarpati, Ottavia Clemente...
https://pubmed.ncbi.nlm.nih.gov/41963331Actively Recruiting
Phase 2
Age: 18Years +
All Genders
ID04893785
A Phase II Single Arm Trial Evaluating the Activity and Safety of Cabozantinib and Temozolomide Combination in Progressive Lung and GEP Neuroendocrine Neoplasms After Prior Treatments
Led by National Cancer Institute, Naples · Updated on 2024-06-18
35
Participants Needed
1
Research Sites
99 weeks
Total Duration
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AI-Summary
What this Trial Is About
Researchers are evaluating the combination of Cabozantinib and Temozolomide in patients with lung and gastro-entero-pancreatic neuroendocrine neoplasms (NENs) that have progressed after first-line treatments such as everolimus, sunitinib, or peptide receptor radionuclide therapy (PRRT). This phase II study aims to assess the safety and activity of this drug combination, addressing the need for new therapies in advanced NENs where standard second-line options are lacking. The study is sponsored by the National Cancer Institute, Naples. Participants will receive Cabozantinib 40 mg orally once daily alongside Temozolomide given at 100 mg/m2/day for seven days followed by seven days off, in repeated 4-week cycles. Treatment continues until disease progression, unacceptable side effects, withdrawal, or death. Patients must attend clinic visits on Days 1, 8, 14, and 22 of each cycle and have an end-of-treatment visit about 30 days after the last dose. After treatment, follow-up continues every three months to monitor survival and further therapies for up to 18 months or six months after the last patient stops treatment. During the study, participants will undergo regular assessments including imaging scans (CT, MRI, and optionally Gallium 68 PET scans) to measure tumor response using RECIST criteria. Researchers will collect data on overall response rate, progression-free survival, clinical benefit, overall survival, duration of response, and safety. They will also evaluate the predictive role of MGMT methylation status. The total study duration for each participant may be up to 42 months, including treatment and follow-up. Safety and tolerability will be closely monitored throughout the trial.
CONDITIONS
Brief Title
A Trial Evaluating the Activity and Safety of Combination Between Cabozantinib and Temozolomide in Lung and GEP-NENS Progressive After Everolimus, Sunitinib or PRRT (CABOTEM)
Who Can Participate
Age: 18Years +
All Genders
Eligibility Criteria
You may qualify if you...
- Patients aged 18 years or older
- Signed informed consent to participate
- Histological or cytological diagnosis of well differentiated Lung and GEP neuroendocrine neoplasms (NET G1, G2, G3) or large cell neuroendocrine carcinoma with Ki67 < 55%
- Disease progression within 12 months prior to study entry
- Measurable disease by RECIST 1.1 criteria on CT or MRI
- Adequate swallowing ability
- Both functional and non-functional tumors eligible
- Stable dose of somatostatin analogues for at least 2 months if used concurrently
- At least 4 weeks washout from prior targeted therapies
- At least 6 months washout from prior PRRT
- ECOG performance status 0 to 2
- Adequate bone marrow, liver, and renal function
- Recovery from prior treatment toxicities unless stable and nonsignificant
- Estimated life expectancy of at least 12 weeks
- Agreement to use effective contraception during and after study according to gender
- Negative pregnancy test for women of child-bearing potential
- Ability to understand and comply with study requirements
You will not qualify if you...
- Anticancer therapy within 4 weeks before study entry
- Previous treatment with Temozolomide or Cabozantinib
- Radiation therapy for bone metastasis within 2 weeks or other radiation within 4 weeks before recruitment
- PRRT within 6 months before study entry
- Ongoing complications from prior radiation therapy or surgery
- Untreated or unstable brain metastases or cranial epidural disease
- Therapeutic anticoagulation with oral anticoagulants or platelet inhibitors
- Chronic hepatitis B infection
- Chronic corticosteroid or immunosuppressive treatment
- Serious illnesses including gastrointestinal disorders with high risk of perforation, cavitating pulmonary lesions, lesions invading major blood vessels, significant bleeding risk, active infections including HIV/AIDS, serious non-healing wounds, malabsorption, uncontrolled hypothyroidism, dialysis requirement, organ transplantation
- Uncontrolled congestive heart failure or cardiac ejection fraction ≤ 40%
- Prolonged QT interval or congenital long QT syndrome
- Rare hereditary disorders affecting sugar metabolism
- Recent major surgery with incomplete wound healing
- Pregnant or lactating females
- History of other malignancies within 2 years except superficial skin cancers
- Serious or unstable medical or psychiatric conditions affecting safety or compliance
- Use of drugs contraindicated with Cabozantinib or Temozolomide according to product information
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
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Your Study Journey
Screening
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Treatment
Duration - Up to 42 months
Participants receive a combination of cabozantinib and temozolomide until disease progression, unacceptable toxicity, withdrawal of consent, or death, whichever comes first.
4 visits per 4-week cycle (Day 1, Day 8, Day 14, and Day 22)
Follow-up
Duration - Until 6 months after the last patient stops study treatment or up to 18 months after the last patient is randomised, whichever is sooner
Participants are followed up every 3 months during routine clinic appointments to collect data on further anti-cancer treatment and survival.
Visits every 3 months
Trial Site Locations
Total: 1 location
1
National Cancer Institute of Naples
Naples, Campania, Italy, 80131
Actively Recruiting
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Research Team
S
Salvatore Tafuto, MD
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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