Study of the Combination of Tivantinib Plus Pemetrexed and Carboplatin

NCT02049060 | Completed Phase 1

• 1 other identifier: ONC-2011-001
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, open-label, mono-centric, phase I-Ib trial of Tivantinib in combination with Pemetrexed and Carboplatin as first-line therapy in patients with advanced or metastatic cancer suitable for a Carboplatin and Pemetrexed regimen as part of their specific therapy.

Conditions

Malignant Pleural Mesothelioma; Nonsquamous Nonsmall Cell Neoplasm of Lung

Keywords

MPM; NSCLC

Outcome Measures

Primary Outcomes (1)

• To determine the dose limiting toxicities (DLTs) of Tivantinib

  1.To determine the dose limiting toxicities (DLTs) of Tivantinib given orally twice daily on a continuous schedule in combination with Carboplatin and Pemetrexed administered intra-venous every 3 weeks.

  18 months

Secondary Outcomes (7)

• To determine the pharmacokinetics profile of Tivantinib in combination with Carboplatin and Pemetrexed

  18 months

• To assess the preliminary anti-tumor activity of Tivantinib with PFS

  18 months

• To assess the preliminary anti-tumor activity of Tivantinib with RECIST

  18 months

• To evaluate dynamic changes in blood levels

  18 months

• To evaluate the expression of biomarkers

  18 months

Study Arms (1)

Tivantinib+carboplatino+pemetrexed

EXPERIMENTAL

•- 1 level: Tivantinib 120 mg p.o. BID + Carboplatin AUC 5 i.v. day 1 every 3 weeks + Pemetrexed 500 mg/mq i.v. day 1 every 3 weeks •0 level: Tivantinib 240 mg p.o. BID + Carboplatin AUC 5 i.v. day 1 every 3 weeks + Pemetrexed 500 mg/mq i.v. day 1 every 3 weeks •+ 1 level: Tivantinib 360 mg p.o. BID + Carboplatin AUC 5 i.v. day 1 every 3 weeks + Pemetrexed 500 mg/mq i.v. day 1 every 3 weeks

Drug: Tivantinib

Interventions

Tivantinib DRUG

•- 1 level: Tivantinib 120 mg p.o. BID + Carboplatin AUC 5 i.v. day 1 every 3 weeks + Pemetrexed 500 mg/mq i.v. day 1 every 3 weeks •0 level: Tivantinib 240 mg p.o. BID + Carboplatin AUC 5 i.v. day 1 every 3 weeks + Pemetrexed 500 mg/mq i.v. day 1 every 3 weeks •+ 1 level: Tivantinib 360 mg p.o. BID + Carboplatin AUC 5 i.v. day 1 every 3 weeks + Pemetrexed 500 mg/mq i.v. day 1 every 3 weeks

Also known as: ARQ 197

Tivantinib+carboplatino+pemetrexed

Eligibility Criteria

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

You may qualify if:

• Patients must be diagnosed with MPM or non squamous NSCLC.
• Age \> 18.
• ECOG Performance Status 0-1 and life expectancy of at least 12 weeks.
• Measurable and/or evaluable lesions according to modified RECIST criteria \[51\].
• Written informed consent.
• Patients must be accessible for treatment and follow up. Patients registered on this trial must be treated and followed at the participating center.
• Patients must use effective contraception during the study lasting at least one month after the end of treatment for both sexes.
• Laboratory requirements:
• Neutrophils \>1.5 x 109/L and Platelets \>100 x 109/L
• Total bilirubin \<1.5 time the upper-normal limits (UNL) of the Institutional normal values, AST (SGOT) and ALT (SGPT) \< 2.5 x UNL, or \<5 x UNL in case of liver metastases, alkaline phosphatase \<2.5 x UNL, \< 5 x UNL in case of liver metastases, \<10 x UNL in case of bone metastases.
• Creatinine clearance \>50 mL/min

You may not qualify if:

• Any prior chemotherapy (including intracavitary administration).
• Symptomatic and/or unstable pre-existing brain metastases.To be enrolled in the study , subjects must have confirmation of stable disease by MRI or computer tomography (CT) scan within 4 weeks from day 1 of cycle 1 of treatment and have CNS metastases well controlled by steroids, anti - epileptics or other symptom-relieving medications
• Serious non-healing wound or ulcer.
• Evidence of bleeding diathesis or coagulopathy.
• Uncontrolled hypertension.
• Clinically significant (i.e. active) cardiovascular disease, for example cerebrovascular accidents (\<6 months), myocardial infarction (\< 6 months), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication.
• Current treatment with anticoagulants for therapeutic purposes.
• Treatment with any investigational drug within 30 days prior to enrolment.
• Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of basal cell carcinoma or cervical cancer in situ
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study treatment start, or anticipation of the need for major surgical procedure during the course of the study.
• Pregnant or lactating women. Women of childbearing potential with either a positive or no pregnancy test at baseline. Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential. Sexually active males and females (of childbearing potential) unwilling to practice contraception during the study.

Sponsors & Collaborators

• Armando Santoro, MD: lead

Study Sites (1)

Istituto Clinico Humanitas

Rozzano, Milan, 20089, Italy

Location

MeSH Terms

Conditions

Mesothelioma, Malignant

Interventions

ARQ 197

Condition Hierarchy (Ancestors)

Mesothelioma; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Armando Santoro, MD

  Istituto Clinico Humanitas

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigators

Study Record Dates

• First Submitted: May 24, 2013
• First Posted: January 29, 2014
• Study Start: January 1, 2013
• Primary Completion: May 1, 2016
• Study Completion: December 1, 2017
• Last Updated: January 22, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)