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A Study of ABTL0812 in Pancreatic Cancer (Pancreatic)

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ClinicalTrials.gov Identifier: NCT03417921
Recruitment Status : Not yet recruiting
First Posted : January 31, 2018
Last Update Posted : June 25, 2019
Sponsor:
Collaborator:
The Cleveland Clinic
Information provided by (Responsible Party):
Ability Pharmaceuticals SL

Tracking Information
First Submitted Date  ICMJE January 22, 2018
First Posted Date  ICMJE January 31, 2018
Last Update Posted Date June 25, 2019
Estimated Study Start Date  ICMJE December 1, 2019
Estimated Primary Completion Date March 30, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 29, 2018)
Emergent Adverse Events [ Time Frame: 1 year ]
Related Adverse Events as Assessed by CTCAE v4.03
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03417921 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of ABTL0812 in Pancreatic Cancer
Official Title  ICMJE 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
Brief 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.
Detailed Description

This is an open-label, randomized phase I/II multicenter study to evaluate ABTL0812 in combination with gemcitabine and nab-paclitaxel at first line therapy. Patients will be assigned to the following groups during the study conduct:

  • GROUP A: You will receive the standard treatment of chemotherapy and the investigational drug ABTL0812.
  • GROUP B: You will receive the standard treatment of chemotherapy.

For GROUP A:

Phase I: A 3+3 de-escalation design followed by an expansion phase will be performed

  • ABTL0812 will be administered chronically daily. Potential dose levels are 1300 mg tid, 1000 mg tid, 650 mg tid and 500 mg tid. Intrapatient escalation or de-escalation is not permitted. A run-in period of one week for ABTL0812 is planned before starting the first cycle of chemotherapy.
  • Chemotherapy will be administered on 28-day cycles: gemcitabine 1000 mg/m2 + nab-paclitaxel 125 mg/m2 on days 1, 8 and 15.
  • If any, or all, the components of the chemotherapeutic regimen must be interrupted for any reason (excluding disease progression), ABTL0812 will be administered as maintenance therapy until disease progression, onset of unacceptable drug toxicities, or patient/physician's request to discontinue.

Phase II:

  • ABTL0812 will be administered chronically daily at the Recommended Phase 2 Dose (RP2D). A run-in period of one week for ABTL0812 is planned before starting the first cycle of chemotherapy.
  • Chemotherapy will be administered on 28-day cycles: gemcitabine 1000 mg/m2 IV + nab-paclitaxel 125 mg/m2 IV on days 1, 8 and 15
  • If any, or all, the components of the chemotherapeutic regimen must be interrupted for any reason (excluding disease progression), ABTL0812 will be administered as maintenance therapy until disease progression, onset of unacceptable drug toxicities, or patient/physician's request to discontinue.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Pancreatic Cancer
Intervention  ICMJE
  • Drug: ABTL0812
    ABTL0812 in combination with gemcitabine and nab-paclitaxel
  • Drug: Gemcitabine and nab-paclitaxel
    Gemcitabine and nab-paclitaxel as standard pattern
Study Arms  ICMJE
  • Experimental: ARM A
    ABTL0812 (starting 1,300 mg tid orally) in combination with gemcitabine and nab-paclitaxel will be administered to patients with pancreatic cancer
    Interventions:
    • Drug: ABTL0812
    • Drug: Gemcitabine and nab-paclitaxel
  • Active Comparator: ARM B
    Gemcitabine and nab-paclitaxel will be administered to patients with pancreatic cancer as standard pattern
    Intervention: Drug: Gemcitabine and nab-paclitaxel
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: September 27, 2018)
110
Original Estimated Enrollment  ICMJE
 (submitted: January 29, 2018)
46
Estimated Study Completion Date  ICMJE March 30, 2023
Estimated Primary Completion Date March 30, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Marc Cortal +93603141706 contact@abilitypharma.com
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03417921
Other Study ID Numbers  ICMJE ABT-C6-2017
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Ability Pharmaceuticals SL
Study Sponsor  ICMJE Ability Pharmaceuticals SL
Collaborators  ICMJE The Cleveland Clinic
Investigators  ICMJE
Principal Investigator: Davendra Sohal Cleveland Clinics
PRS Account Ability Pharmaceuticals SL
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP