Patient with Lung and GEP-NENs progressive after SSAr, everolimus, sunitinib or PRRT. MedDRA version: 20.0 Level: HLT Classification code 10028196 Term: Multiple endocrine neoplasias System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Temodal
Product Name: Temozolomide
Product Code: [Temozolomide]
Pharmaceutical Form: Tablet
INN or Proposed INN: TEMOZOLOMIDE
Current Sponsor code: Temozolomide
Concentration unit: mg/m2 m
Sponsors
ISTITUTO NAZIONALE TUMORI - IRCCS FONDAZIONE PASCALE
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. 18 years and older patients 2. Signed informed consent prior to initiation of any study-specific procedures or treatment, as confirmation of the patient’s awareness and willingness to comply with the study requirements. 3. Documented histological or cytological diagnosis of well differentiated Lung and GEP-NENs (NET G1, NET G2, NET G3 in WHO 2017 classification) progressing after a first line of therapy with SSAs, sunitinib, everolimus, chemotherapy and/or PRRT or documented histological or cytological diagnosis of Large cells neuroendocrine carcinoma patients with Ki67=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1. Receipt of any type of anticancer therapy within 4 weeks before study entry. 2. Previous treatment with Temozolomide or cabozantinib 3. Radiation therapy for bone metastasis within 2 weeks, any other external radiation therapy within 4 weeks before recruitment. 4. Previous PRRT treatment: Systemic treatment with radionuclides within 6 months before study entry. 5. Subjects with clinically relevant ongoing complications from prior radiation therapy and/or surgery are not eligible. 6. Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery and stable for at least 3 months before study entry 7. Concomitant anticoagulation at therapeutic doses with oral anticoagulants or platelet inhibitors. 8. Chronic treatment with corticosteroids or other immuno-suppressive agents. 9. Serious illness other than cancer: a. Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation: i. Tumors invading the GI tract, active peptic ulcer disease, inflammatory bowel disease (eg, Crohn’s disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis or acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction ii. Abdominal fistula, GI perforation, bowel obstruction, intra-abdominal abscess within 6 months before recruitment. Note: Complete healing of an intra-abdominal abscess must be confirmed prior to recruitment. b. Cavitating pulmonary lesion(s) or endobronchial disease c. Lesion invading a major blood vessel including, but not limited to: inferior vena cava, pulmonary artery, or aorta. Subjects with lesions invading the portal vasculature are eligible. d. Clinically significant bleeding risk including the following within 3 months of recruitment: hematuria, hematemesis, hemoptysis of >0.5 teaspoon (>2.5 mL) of red blood, or other signs indicative of pulmonary hemorrhage, or history of other significant bleeding if not due to reversible external factors e. Other clinically significant disorders such as: i. Active infection requiring systemic treatment, known infection with human immunodeficiency virus (HIV), or known acquired immunodeficiency syndrome (AIDS)-related illness. ii. Serious non-healing wound/ulcer/bone fracture iii. Malabsorption syndrome iv. Uncompensated/symptomatic hypothyroidism v. Requirement for hemodialysis or peritoneal dialysis vi. History of solid organ transplantation 4. Uncontrolled congestive heart failure (NYHA II, III, IV). Patients with history of congestive heart failure who do not violate this exclusion criterion will undergo an evaluation of their cardiac ejection fraction prior to recruitment, preferably via gated equilibrium radionuclide ventriculography. The results from an earlier assessment (not exceeding 30 days prior to recruitment) may substitute the evaluation at the discretion of the Investigator, if no clinical worsening is noted. The patient’s measured cardiac ejection fraction in these patients must be >40% before recruitment. 5. QTcF > 470 msec for females and QTcF > 450 msec for males or congenital long QT syndrome. 6. Patients with rare hereditary problems of galattose intolerance, congenital lactase deficiency or glucose-galattose malabsorption. 7. Major surgery within 3 months before study entry. Complete wound healing from major surgery must have occurred 1 month before study entry and from minor surge
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of the combination of cabozantinib and one-week-on one-week-off temozolomide, based on overall response rate (ORR).;Secondary Objective: 1.To assess the activity of the combination of cabozantinib and one-week-on one-week-off temozolomide according to Progression Free Survival (PFS), Clinical Benefit Rate (CBR), Overall Survival (OS), duration of response (DOR). 2.To assess the safety and tolerability of the combination of cabozantinib and one-week-on one-week-off temozolomide. 3.To assess the predictive role of MGMT Methylation Status on response to the combination of cabozantinib and one-week-on one-week-off temozolomide. 4.To assess the activity of the combination of cabozantinib and one-week-on one-week-off temozolomide at 1 year from the start of the treatment.;Primary end point(s): ORR (as assessed by RECIST v1.1) defined by complete response (CR) or partial response (PR).;Timepoint(s) of evaluation of this end point: 2 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): PFS (as assessed by RECIST v1.1) defined as time from study entry to first evidence of disease progression or death due to any cause. CBR (as assessed by RECIST v1.1) defined by complete response (CR) or partial response (PR) or stable disease (SD). OS defined as time from study entry to death due to any cause or to study termination. DOR defined as time from study entry to change in response from CR or PR to Stable Disease (SD) or Progressive Disease (SD) (as assessed by RECIST v1.1). Safety and tolerability as assessed by adverse events according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 MGMT Methylation Status will be assessed and any correlation with the efficacy endpoints will be evaluated. 1 year overall survival (OS);Timepoint(s) of evaluation of this end point: 1 year | — |
Countries
Italy
Contacts
Public ContactSC ONCOLOGIA CLINICA SPERIMENTALE A
ISTITUTO NAZIONALE TUMORI IRCCS FONDAZIONE G. PASCALE
Outcome results
None listed