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)

NCT04893785 | Recruiting Phase 2 DMC

• 1 other identifier: CABOTEM
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of CABOTEM study is to demonstrate the safety and activity of the Cabozantinib and Temozolomide combination in Lung and GEP-NENs patients, progressing after a first line therapy, including target therapies (everolimus, sunitinib) and / or chemotherapy, in the approved setting.

Conditions

Lung Neuroendocrine Neoplasm; GEP Neuroendocrine Tumor

Outcome Measures

Primary Outcomes (1)

• To assess the efficacy of the combination of cabozantinib and one-week-on/one-week-off temozolomide, based on overall response rate (ORR).

  Overall Response Rate (ORR) (as assessed by RECIST v1.1) defined by complete response (CR) or partial response (PR).

  Up to 42 months

Secondary Outcomes (7)

• To assess the activity of the combination of cabozantinib and one-week-on one-week-off temozolomide according to Progression Free Survival (PFS)

  Up to 42 months

• To assess the activity of the combination of cabozantinib and one-week-on one-week-off temozolomide according to Clinical Benefit Rate (CBR)

  Up to 42 months

• To assess the activity of the combination of cabozantinib and one-week-on one-week-off temozolomide according to Overall Survival (OS)

  Up to 42 months

• To assess the activity of the combination of cabozantinib and one-week-on one-week-off temozolomide according to duration of response (DOR)

  Up to 42 months

• To assess the safety and tolerability of the combination of cabozantinib and one-week-on one-week-off temozolomide

  Up to 42 months

Study Arms (1)

Cabozantinib and Temozolomide

EXPERIMENTAL

All patients will receive: * Cabozantinib 40 mg os QD * Temozolomide 100 mg/m2/day seven days followed by seven days of stop (regimen one week on / one week off).

Drug: Cabozantinib and Temozolomide

Interventions

Cabozantinib and Temozolomide DRUG

Patients enrolled will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever comes first. Patients will be required to attend clinic on Day 1, Day 8, Day 14 and Day 22 of every 4 week cycle. Patients will return to clinic at 30 days (+/- 5 days) of their last dose of cabozantinib or temozolomide (whichever is discontinued last), for an end of treatment visit. Following their end of treatment visit patients will be followed-up 3-monthly during routine clinic appointments to collect data on further anti-cancer treatment and survival. Follow-up will continue until 6 months after the last patient stops study treatment or up to 18 months after the last patient is randomised, whichever is sooner.

Cabozantinib and Temozolomide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years and older patients.
• 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.
• 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\< 55% progressed after platinum-based first line chemotherapy.
• Subjects must have evidence of progressed disease, radiologically documented in the 12 months previous study entry.
• Subjects must have evidence of measurable disease as determined by the investigator. Target lesions must have shown evidence of disease progression by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 criteria in the 12 months prior to study entry. Patients must have measurable disease per RECIST 1.1 by computer tomography (CT) scan or magnetic resonance imaging (MRI). Gallium 68 PET Scan can be considered useful before and during the treatment.
• Subject must have adequate swallowing capacity.
• Subjects with functional (associated with a clinical hormone syndrome) and non functional tumors are eligible for the study.
• The concurrent use of somatostatin analogues is allowed provided that the patient has been on a stable dose for at least two months.
• At least 4 weeks of wash-out from previous targeted therapies.
• At least 6 months of wash-out from previous PRRT treatment.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2.
• Subjects must have adequate organ function, including the following:
• Bone marrow reserve consistent with: absolute neutrophil count (ANC) ≥1.5 x109/L; platelet count ≥ 100 x 109/L; haemoglobin ≥ 9 g/dL;
• Hepatic: total bilirubin ≤ 1.5 x upper limit of normal (ULN), transaminases (aspartate aminotransferase/serum glutamic oxaloacetic transaminase \[AST/SGOT\] and alanine aminotransferase/serum glutamic pyruvic transaminase \[ALT/SGPT\]) ≤ 2.5 x ULN (\< 5 x ULN if liver metastases are present);
• Renal: normal serum creatinine or calculated creatinine clearance ≥ 60 mL/min (Cockroft-Gault formula);

You may not qualify if:

• Receipt of any type of anticancer therapy within 4 weeks before study entry.
• Previous treatment with Temozolomide or cabozantinib
• Radiation therapy for bone metastasis within 2 weeks, any other external radiation therapy within 4 weeks before recruitment.
• Previous PRRT treatment: Systemic treatment with radionuclides within 6 months before study entry.
• Subjects with clinically relevant ongoing complications from prior radiation therapy and/or surgery are not eligible.
• 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
• Concomitant anticoagulation at therapeutic doses with oral anticoagulants or platelet inhibitors.
• Chronic hepatitis B infection (both active or not).
• Chronic treatment with corticosteroids or other immuno-suppressive agents.
• Serious illness other than cancer including, but not limited to, the following conditions:
• Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation: i.e. 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.
• Cavitating pulmonary lesion(s) or endobronchial disease
• 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.
• 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

Sponsors & Collaborators

• National Cancer Institute, Naples: lead

Study Sites (1)

National Cancer Institute of Naples

Naples, Campania, 80131, Italy

RECRUITING

MeSH Terms

Conditions

Gastro-enteropancreatic neuroendocrine tumor

Interventions

cabozantinib; Temozolomide

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Central Study Contacts

Salvatore Tafuto, MD

CONTACT

081 5903 680; s.tafuto@istitutotumori.na.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2021
• First Posted: May 20, 2021
• Study Start: June 15, 2021
• Primary Completion: January 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: June 18, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)