Overview

A Study of ABTL0812 in Pancreatic Cancer

Status:
Not yet recruiting
Trial end date:
2023-03-30
Target enrollment:
0
Participant gender:
All
Summary
A Randomized 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.
Phase:
Phase 1/Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Ability Pharmaceuticals SL
Collaborator:
The Cleveland Clinic
Treatments:
Albumin-Bound Paclitaxel
Gemcitabine
Paclitaxel
Criteria
Inclusion Criteria:

- Patients ≥18 years of age

- 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 AST (SGOT) ≤ 2.5 times x upper limit of normal (ULN) and 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:

Inclusion criteria:

Patients fulfilling the following criteria are eligible for participation in the study:

- Patients ≥18 years of age

- 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 AST (SGOT) ≤ 2.5 times x upper limit of normal (ULN) and 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:

Patients who meet one of more of the following criteria are not eligible:

- Patients with neuroendocrine tumors or cystic neoplasms are excluded

- 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 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.