A Phase I/II Study of ABTL0812 (Pancreatic)

Pancreatic Cancer Clinical Trial

— Pancreatic  

Official title:

A Phase I/II Open Label Study to Assess the Efficacy and Safety of ABTL0812 in Combination With Gemcitabine and Nab-paclitaxel in Patients With Advanced Metastatic Pancreatic Cancer at First Line Therapy

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03362892
• Other study ID #: ABT-C6-2017
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• First received: November 30, 2017
• Last updated: December 5, 2017
• Start date: July 1, 2018
• Est. completion date: July 1, 2021

Study information

• Verified date: November 2017
• Source: Ability Pharmaceuticals SL
• Contact: Marc Cortal
• Phone: 603706141
• Email: marc.cortal[@]abilitypharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A phase I/II open label study to assess the efficacy and safety of ABTL0812 in combination with gemcitabine and nab-paclitaxel in patients with advanced metastatic pancreatic cancer at first line therapy and as maintenance therapy after chemotherapy

Description:

This is a phase I/II study with differentiated endpoints for each phase. For phase I, primary endpoint will be focused on safety and for phase II, primary endpoint will be focused on efficacy.

Phase I:

Primary • To assess safety and tolerability and to identify the maximum tolerated dose (MTD), dose-limiting toxicities (DLT) and the Recommended Phase II Dose (RP2D) of ABTL0812 plus gemcitabine + nab-paclitaxel at first line therapy.

Secondary

• To evaluate the efficacy of ABTL0812 plus gemcitabine + nab-paclitaxel and as maintenance therapy after chemotherapy

• To evaluate the pharmacokinetics of ABTL0812 alone and in combination with gemcitabine + nab-paclitaxel

• To evaluate biomarkers to monitor activity ABTL0812 in combination with gemcitabine + nab-paclitaxel

Phase II:

Primary

• To evaluate progression-free survival at 6 months (PFS-6m) according to RECIST guidelines.

Secondary

• To evaluate PFS and PFS-12m

• To evaluate tumor response according to Response Evaluation Criteria in Solid Tumors (RECIST) guidelines

• To evaluate overall survival (OS)

• To assess safety and tolerability of ABTL0812 plus gemcitabine + nab-paclitaxel according to CTACE v4.03

• To evaluate the pharmacokinetics of ABTL0812 alone and in combination with gemcitabine + nab-paclitaxel

• To evaluate the pharmacodynamics of ABTL0812 in blood alone and in combination with gemcitabine + nab-paclitaxel

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 46
• Est. completion date: July 1, 2021
• Est. primary completion date: July 1, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Willing and able to provide informed consent

• Ability and willingness to comply with study visits, treatment, testing, and to comply with the protocol

• Patient has histologically or cytologically confirmed metastatic adenocarcinoma of the pancreas. The definitive diagnosis of metastatic pancreatic adenocarcinoma will be made by integrating the histopathological data within the context of the clinical and radiographic data. Patients with islet cell neoplasms are excluded. Initial diagnosis of metastatic disease must have occurred =6 weeks prior to inclusion in the study.

• Patient has one or more metastatic tumors measurable by CT scan (or MRI, if patient is allergic to CT contrast media).

• Patient has not received previous radiotherapy, surgery, chemotherapy or investigational therapy for the treatment of metastatic disease. Prior treatment with 5-FU or gemcitabine administered as a radiation sensitizer in the adjuvant setting is allowed, provided at least 6 months have elapsed since completion of the last dose and no lingering toxicities are present.

• Patient has not received cytotoxic doses of gemcitabine or any other chemotherapy in the adjuvant setting

• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.

• Adequate hematologic function, measured as:

• absolute neutrophil count = 1.5x109/L

• platelet count = 100x109/L

• hemoglobin = 9.0 g/dL

• Total bilirubin = 1.5 x ULN

• Albumin = 1.5 x ULN

• Aspartate transaminase (AST) (SGOT) = 2.5 times x upper limit of normal (ULN) and Alanine transaminase (ALT) (SGPT) < 2.5 times x upper limit of normal (=5 times the ULN in patients with evidence of liver metastases)

• Alkaline phosphatase = 2.5 times ULN (=5 times the ULN in patients with evidence of liver metastases)

• Serum creatinine =1.5 ULN

• Have adequate tumor tissue available (either archival or new tumor biopsy) for biomarker analyses. The most recently collected tumor tissue sample should be provided, if available.

• Life expectancy = 12 weeks in the opinion of the investigator

• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 guidelines with at least one "target lesion" to be used to assess response. Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented

• Contraception: All female patients will be considered to be of childbearing potential unless they are postmenopausal (at least 12 months' consecutive amenorrhea, in the appropriate age group and without other known or suspected cause), or have been sterilized surgically. Female patients of childbearing potential must agree to use two forms of highly effective contraception methods during the study and for a period of 6 months following the last administration of the study drug. Male patients and their female partners, who are of childbearing potential and are not practicing total abstinence, must agree to use two forms of highly effective contraception during the study and for a period of 6 months following the last administration of the study drug.

• Toxicities incurred as a result of previous anticancer therapy (radiation therapy, chemotherapy, or surgery) must be resolved to = grade 1 (as defined by Common Terminology Criteria for Adverse Events version 4.03).

Exclusion Criteria:

• Patient has received previous radiotherapy, surgery, chemotherapy or investigational therapy for the treatment of metastatic disease. Prior treatment with 5-FU or gemcitabine administered as a radiation sensitizer in the adjuvant setting is allowed, provided at least 6 months have elapsed since completion of the last dose and no lingering toxicities are present. Patients having received cytotoxic doses of gemcitabine or any other chemotherapy in the adjuvant setting are not eligible for this study

• Patient has only locally advanced disease.

• Patients has symptomatic brain metastases. Patients with asymptomatic brain metastases can be included in the study if they are kept on stable doses of steroids for a period of 1 month prior to study entry provided they don't have peripheric neuropathy grade 2 or superior.

• Patients previously treated with an inhibitor of the Phosphoinositide 3-kinase/Protein kinase B/mechanistic target of rapamycin (PI3K/Akt/mTOR) pathway

• Patients has gastrointestinal abnormalities including inability to take oral medications, malabsorption syndromes or other clinically significant gastrointestinal abnormalities that may impair the absorption of the investigational medicinal product.

• Pregnancy or lactation. Serum pregnancy test to be performed within 7 days prior to study treatment start.

• Patients had myocardial infarction within = 12 months prior to study entry, symptomatic congestive heart failure (New York Heart Association > class II), unstable angina pectoris, or unstable cardiac arrhythmia requiring medication.

• Evidence of pre-existing uncontrolled hypertension. Patients whose hypertension is controlled by antihypertensive therapies are eligible.

• Patients has active Hepatitis B or C or human immunodeficiency virus (HIV) infection with non-controlled disease according to the treating physician.

Patients with any other medical conditions (such as psychiatric illness, infectious diseases, abnormal physical examination or laboratory findings) that in the opinion of the investigator may interfere with the planned treatment, affect patient compliance or place the patient at high risk from treatment-related complications.

Related Conditions & MeSH terms

• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Drug:
• sodium 2-hydroxylinoleate
sodium 2-hydroxylinoleic (starting 1,300 mg tid orally) in combination with gemcitabine and nab-paclitaxel will be given to patients with advanced metastatic pancreatic cancer

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Ability Pharmaceuticals SL

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Emergent Adverse Events	Related Adverse Events as Assessed by CTCAE v4.03	2 years
Secondary	Progression Free Survival (PFS)	Progression Free Survival (PFS) based on tumor assessment by CT-Scan according to RECIST criteria version 1.1. performed at baseline and at every other treatment visit, starting at 3rd SOC cycle	2 years