Clinical Trials /

Procaspase Activating Compound-1 (PAC-1) in the Treatment of Advanced Malignancies - Component 1

NCT02355535

Description:

This Phase I dose escalation study will evaluate Procaspase Activating Compound-1 (PAC-1), a small molecule that activates procaspase -3 to caspase-3, resulting in apoptosis of cancer cells, in patients with advanced malignancies. As of March 1, 2019, only patients with neuroendocrine tumors will be enrolled in Component 1 of this study. PAC-1 is taken orally on days 1-21 of a 28-day cycle. The maximum tolerated dose (MTD) of PAC-1 (5 dose levels) will be determined using a modified-Fibonacci dose-escalation 3+3 design. Treatment continues until disease progression, unacceptable toxicity, physician discretion, or patient refusal.

Related Conditions:
  • Lymphoma
  • Malignant Solid Tumor
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Procaspase Activating Compound-1 (PAC-1) in the Treatment of Advanced Malignancies - Component 1
  • Official Title: (STM-03) Phase I Study of Procaspase Activating Compound-1 (PAC-1) in the Treatment of Advanced Malignancies - Component 1

Clinical Trial IDs

  • ORG STUDY ID: 2015-0057
  • NCT ID: NCT02355535

Conditions

  • Solid Tumor
  • Pancreatic Neuroendocrine Tumor
  • Neuroendocrine Tumors

Interventions

DrugSynonymsArms
PAC-1Procaspase Activating Compound-1Open label

Purpose

This Phase I dose escalation study will evaluate Procaspase Activating Compound-1 (PAC-1), a small molecule that activates procaspase -3 to caspase-3, resulting in apoptosis of cancer cells, in patients with advanced malignancies. As of March 1, 2019, only patients with neuroendocrine tumors will be enrolled in Component 1 of this study. PAC-1 is taken orally on days 1-21 of a 28-day cycle. The maximum tolerated dose (MTD) of PAC-1 (5 dose levels) will be determined using a modified-Fibonacci dose-escalation 3+3 design. Treatment continues until disease progression, unacceptable toxicity, physician discretion, or patient refusal.

Trial Arms

NameTypeDescriptionInterventions
Open labelExperimentalUsing a dose-escalation design, PAC-1 is administered orally on days 1-21, at the assigned dose, of a 28-day cycle.
  • PAC-1

Eligibility Criteria

        Inclusion Criteria:

          1. Male or female ≥ 18 years of age

          2. Diagnosis of advanced solid tumor or hematologic malignancy (limited to lymphoma) that
             has failed or become intolerant to standard therapy

          3. Has measurable disease, defined as at least 1 tumor that fulfills the criteria for a
             target lesion according to RECIST 1.1, or lymphoma that fulfills the Deauville PET
             Criteria

          4. Has an ECOG PS of 0, 1, or 2

          5. Has total bilirubin < 1.5 mg/dL, serum albumin > 3.0 gm/dL, AST and ALT < 1.5 ULN or <
             3 x ULN for subjects with known hepatic metastases

          6. Has serum creatinine < 1.5 × ULN

          7. Has hemoglobin ≥ 10 g/dL, ANC ≥ 1.5 × 109/L, and platelet count ≥ 100 × 109/L

          8. Must be able to take oral medication and to maintain a fast as required for 2 hours
             before and 1 hour after capsule(s) administration

          9. Must be willing and able to comply with study

         10. Has read, understood, and signed the ICF

         11. Women of childbearing potential must not be pregnant or breast-feeding. In addition, a
             medically acceptable method of birth control must be used or total abstinence. Women
             who are postmenopausal for at least 1 year or surgically sterile (bilateral tubal
             ligation, bilateral oophorectomy, or hysterectomy) are not considered to be WOCP

         12. Men who are not surgically or medically sterile must agree to use an acceptable method
             of contraception. Male patients with female sexual partners who are pregnant, possibly
             pregnant, or who could become pregnant during the study must agree to use condoms at
             least one month after the last dose of study drug. Total abstinence for the same study
             period is an acceptable alternative

         13. Prior systemic treatments for metastatic disease are permitted but may not be ongoing,
             including targeted therapies, biologic response modifiers, chemotherapy, hormonal
             therapy, or investigational therapy

         14. Willingness to donate blood for biomarker studies related to the type of therapies
             used in this trial and the tumor types being treated

        Exclusion Criteria:

          1. Had surgery within 4 weeks prior to study treatment except for minor procedures
             (hepatic biliary stent placement is allowed)

          2. Gliomas are excluded, as well as any history of brain metastases, seizures or
             underlying brain injury

          3. May not have received cytotoxic chemotherapy, targeted therapies, biologic response
             modifiers, chemotherapy, and hormonal therapy within the last 3 weeks, or nitrosureas
             within the last 6 weeks prior to study treatment.

          4. Has a history of blood clots, pulmonary embolism, or DVT unless controlled by
             anticoagulant treatment

          5. Has a history of an arterial thromboembolic event within the prior six months
             including CVA, TIA, MI, or unstable angina

          6. Has uncontrolled HIV or hepatitis B or C

          7. Has any clinically significant infection

          8. Has any other severe, uncontrolled medical condition, including uncontrolled DM or
             unstable CHF

          9. Radiation therapy to more than 25% of the bone marrow

         10. Prior allogeneic bone marrow or organ transplantation

         11. > Grade 1 peripheral neuropathy within 14 days before enrollment.

         12. Patient has received other investigational drugs with 14 days before enrollment

         13. Other severe acute or chronic medical or psychiatric conditions or laboratory
             abnormality that may increase the risk associated with study participation

         14. Abnormalities on 12-lead electrocardiogram (ECG) considered by the investigator to be
             clinically significant (such as acute ischemia, left bundle branch block, ventricular
             arrhythmias) or baseline prolongation of the rate-corrected QT interval (e.g.,
             repeated demonstration of QTc interval > 480 milliseconds)

         15. Presence of any non-healing wound, fracture, or ulcer

         16. Has any condition that, in the opinion of the investigator, might jeopardize the
             safety of the patient or interfere with protocol compliance

         17. Has any mental or medical condition that prevents the patient from giving informed
             consent
      
Maximum Eligible Age:85 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerated Dose
Time Frame:Up to 30 days post last dose
Safety Issue:
Description:The primary objective of this study component is to determine the maximum tolerated dose (MTD) of PAC-1 in patients with advanced, previously treated malignancy, by evaluation of toxicity and tolerability.

Secondary Outcome Measures

Measure:Adverse Effects
Time Frame:Up to 30 days post final dose
Safety Issue:
Description:Characterize adverse effects (AE) of PAC-1 in patients with advanced malignancy.
Measure:Disease Response based on RECIST Criteria for patients with solid tumors
Time Frame:Up to 8 weeks following final dose
Safety Issue:
Description:Evaluate clinical response of PAC-1 in patients with solid tumors (RECIST v 1.1).
Measure:Disease Response based on Deauville PET Criteria for patients with lymphoma
Time Frame:Up to 8 weeks following final dose
Safety Issue:
Description:Evaluate clinical response of PAC-1 in patients with lymphoma (Deauville PET Criteria).

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Vanquish Oncology, Inc.

Trial Keywords

  • refractory
  • intolerant
  • solid tumors
  • PNET
  • neuroendocrine

Last Updated

March 8, 2019