Clinical trial NCT04122911: Temozolomide for Second-Line Treatment of Neuroendocrine Carcinomas
Official title: A Phase II Single Arm Trial Evaluating the Efficacy and Safety of Temozolomide for Second-Line Treatment of Neuroendocrine Carcinomas Progressing After First-Line Platinum- Based Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Neuroendocrine Carcinomas
Keywords: Temozolomide
second-line chemotherapy
Lead sponsor: National Cancer Institute, Naples
Sponsor class: OTHER
First posted: 2019-10-10
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To assess the efficacy and safety of Temozolomide for second-line treatment of Neuroendocrine Carcinomas progressing after first-line Platinum-based therapy.


Eligibility criteria: Inclusion Criteria:

* 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.
* Patients ≥18 years of age.
* Histologically confirmed Metastatic Neuroendocrine Carcinoma (Ki67\>20% Ki67 must be quantified in percentage) with documented progression of disease per investigator assessment following or during first-line platinum-based treatment.
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2.
* At least 28 days since prior radiation therapy or surgery and recovery from treatment.
* Patients must have measurable disease which must be evaluable per RECIST v1.1.
* Estimated life expectancy of ≥12 weeks.

Exclusion Criteria:

* - Patients \< 18 years of age
* Diagnosis of well differentiated G1/G2 NEN
* Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would prevent the patient from meeting the study requirements.
* Serious active infection requiring i.v. antibiotics and/or hospitalization at study entry.
* Patients who are treated with any medicinal product that contraindicates the use of the study drug, may interfere with the planned treatment, affects patient compliance or puts the patient at high risk for treatment-related complications.
* Pregnant or lactating females. Serum pregnancy test to be assessed within 7 days prior to study treatment start, or within 14 days with a confirmatory urine pregnancy test within 7 days prior to study treatment start. Women of childbearing potential (defined as \<2 years after last menstruation and not surgically sterile) not using effective, non-hormonal means of contraception (intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly). Perimenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential
* Patients with meningeal carcinomatosis
* Patients with organ allografts requiring immunosuppression
* Patients with known positive HIV status
* Patients with a hypersensitivity to Temozolomide or Dacarbazine
* Any laboratory values at baseline as follows:

Hematology:

1. Absolute Neutrophil Count (ANC) \<1.5x109/L or 1500/mm3
2. Platelet count \<100x109/L
3. Hemoglobin \<8 g/dL (Note: hemoglobin levels may be supported by transfusion or erythropoietin or other approved hematopoietic growth factors).

Coagulation:

1. International Normalized Ratio (INR) \>1.5 except for patients on stable anticoagulant therapy
2. Activated Partial Thromboplastin Time (aPTT) ≥1.5 times upper limit of normal (ULN) or greater than the lower limit of the therapeutic range Note: The use of full-dose oral or parenteral anticoagulants is permitted as long as the INR or aPTT is within therapeutic limits (according to the medical standard in the institution) and the patient has been on a stable dose of anticoagulants for at least two weeks at the time of Day 1, Cycle 1.

Serum chemistry:

1. Total bilirubin \>1.5 times ULN
2. Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) \>2 times ULN (\>5 times ULN for patients with known liver involvement)
3. Alkaline Phosphatase (ALP) \>2 times ULN (\>5 times ULN for patients with known liver involvement and \>7 times ULN for patients with known bone involvement).

Primary outcomes:
measure: Overall response rate (ORR)
timeFrame: 6 months
Secondary outcomes:
measure: Second Line Progression Free Survival (PFS)
timeFrame: 12 months
measure: Overall survival (OS)
timeFrame: 12 months
measure: Clinical Benefit Rate (CBR)
timeFrame: 12 month
measure: Safety and tolerability - Incidence of treatment-related adverse events (AE).
timeFrame: 1 month
measure: Safety and tolerability - Incidence of abnormal laboratory test results
timeFrame: 1 month
measure: Safety and tolerability - Incidence of abnormal vital signs
timeFrame: 1 month
measure: Safety and tolerability - Incidence of abnormal ECG readings
timeFrame: 1 month
measure: Quality of Life (QoL) - QoL will be assessed using the European Organization for Research and Trial in Cancer QOL core (EORTC QLQ-C30) questionnaire (version 3) [Quality of life questionnaire - QLQ]
timeFrame: 1 month
measure: Quality of Life (QoL) - QoL will be assessed using disease specific modules for Neuroendocrine Tumors (NET), the EORTC QLQ GINET21 (EORTC QLQ Gastrointestinal Neuroendocrine Tumors 21).
timeFrame: 1 month
Other outcomes:
Locations:
city: Napoli
country: Italy
facility: Istituto Tumori di Napoli - Fondazione G. Pascale
state: Campania
Study officials:
References: