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Procaspase Activating Compound-1 (PAC-1) in the Treatment of Advanced Malignancies - Component 2

This study is currently recruiting participants.
Verified October 2017 by Vanquish Oncology, Inc.
Sponsor:
ClinicalTrials.gov Identifier:
NCT03332355
First Posted: November 6, 2017
Last Update Posted: November 7, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
University of Illinois at Chicago
Information provided by (Responsible Party):
Vanquish Oncology, Inc.
  Purpose
The primary objectives of this study are to determine the maximal tolerated dose (MTD) of PAC-1 in combination with temozolomide in patients with high grade glioma: glioblastoma multiforme (GBM) or anaplastic astrocytoma after progression following standard first line therapy (Component 2), by evaluation of toxicity and tolerability.

Condition Intervention Phase
Glioblastoma Multiforme Anaplastic Astrocytoma Drug: PAC-1 Compound Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Intervention Model Description:
PAC-1 in combination with temozolomide (Component 2): after the MTD is established for single agent PAC-1 in Component 1, a modified-Fibonacci dose-escalation 3+3 design starts in Component 2, at a PAC-1 dose one level lower than the MTD of PAC-1 established in the single agent PAC-1 component (i.e., Component 1) and 150 mg/m2 dose of temozolomide given for the 5 days starting at day 8 of cycle 1 in cohorts of 3-6 patients. The combination cohort that reaches MTD will expanded to at least 9 patients, similar to the PAC-1 alone cohort at MTD.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: (STM-03) Phase I Study of Procaspase Activating Compound-1 (PAC-1) in the Treatment of Advanced Malignancies - Component 2

Resource links provided by NLM:


Further study details as provided by Vanquish Oncology, Inc.:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) [ Time Frame: During treatment cycle 1 (first 28 days) ]
    MTD, defined as the highest tolerated dose of PAC-1 tested in combination with temozolomide in patients with high grade glioma.


Secondary Outcome Measures:
  • Adverse Effects [ Time Frame: Up to 30 days post final dose ]
    Toxicity will be graded using the Common Terminology Criteria for Adverse Events version 4 (CTCAE v4)

  • Disease Response [ Time Frame: Through study completion, an average of one year ]
    Disease response will be assessed by RANO criteria.


Estimated Enrollment: 9
Actual Study Start Date: October 1, 2017
Estimated Study Completion Date: June 30, 2019
Estimated Primary Completion Date: December 31, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PAC-1 in combination with temozolomide
Temozolomide (PO) will be dosed at 150 mg (adjusted for body size area [m2]) daily for 5 days starting on day 8 at cycle 1, and then for each successive cycle. In Component 2, the first PAC-1 dose will be 1 dose level lower than the PAC-1 MTD established in Component 1, and the maximum dose will not exceed 450 mg. PAC-1 will be taken in the morning on days 1-21 in each 28-day cycle.
Drug: PAC-1 Compound
PAC-1 in combination with temozolomide (Component 2): after the MTD is established for single agent PAC-1 in Component 1, a modified-Fibonacci dose-escalation 3+3 design starts in Component 2, at a PAC-1 dose one level lower than the MTD of PAC-1 established in the single agent PAC-1 component (i.e., Component 1). PAC-1 will be taken in the morning on days 1-21 in each 28 day cycle. Temozolomide 150 mg/m2 dose is given for the 5 days starting at day 8 of cycle 1 in cohorts of 3-6 patients. The combination cohort that reaches MTD will expanded to at least 9 patients, similar to the PAC-1 alone cohort at MTD.
Other Name: Temozolamide

Detailed Description:
PAC-1 in combination with temozolomide (Component 2): after the MTD is established for single agent PAC-1 in Component 1, a modified-Fibonacci dose-escalation 3+3 design starts in Component 2, at a PAC-1 dose one level lower than the MTD of PAC-1 established in the single agent PAC-1 component (i.e., Component 1) and 150 mg/m2 dose of temozolomide given for the 5 days starting at day 8 of cycle 1 in cohorts of 3-6 patients. The combination cohort that reaches MTD will expanded to at least 9 patients, similar to the PAC-1 alone cohort at MTD. For all dose cohorts, pharmacokinetics of PAC-1 will be assessed following doses administered on days 1 and 11 of the first cycle. Temozolomide pharmacokinetics will be performed on Day 11 of the first cycle.
  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 (Component 1 - single agent PAC-1) Note: Gliomas are excluded from Component 1 (see exclusion #19)
  3. Diagnosis of high grade glioma: glioblastoma multiforme (GBM) or anaplastic astrocytoma after progression following treatment with standard first line therapy (Component 2 - PAC-1 in combination with temozolomide).
  4. Has measurable disease, defined as at least 1 tumor that fulfills the criteria for a target lesion according to RECIST 1.1 (Component 1).
  5. For patients in study Component 2 measurable disease RANO criteria will be used.
  6. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 (see Appendix 4)
  7. Has adequate hepatic function defined as total bilirubin < 1.5 mg/dL, serum albumin > 3.0 gm/dL, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 1.5 × upper limit of normal (ULN) or < 3 x ULN for subjects with known hepatic metastases
  8. Has adequate renal function defined as serum creatinine < 1.5 × ULN
  9. Has adequate bone marrow function defined as a hemoglobin ≥ 10 g/dL, absolute neutrophil count (ANC) ≥ 1.5 × 109/L, and platelet count ≥ 100 × 109/L
  10. Patients taking antiepileptic drugs (AED) must be on stable doses of AED for at least two weeks prior to registration and have no episode of seizures for at least 14 days prior to registration. Because some AEDs enhance or inhibit enzymes that may affect PAC-1 metabolism, those AEDs will not be permitted in this study. The AEDs that are and are not permissible are in Appendix 6.
  11. Patient 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
  12. Must be willing and able to comply with study visits and procedures
  13. Has read, understood and signed the informed consent form (ICF) approved by the Institutional Review Board/Independent Ethics Committee (IRB/IEC)
  14. Women of childbearing potential (WOCP) must not be pregnant (confirmed by a negative pregnancy test, with a serum B-HCG with a sensitivity of 50 mL U/L within 7 days of study treatment) or breast-feeding. In addition, a medically acceptable method of birth control must be used such as an oral, implantable, injectable, or transdermal hormonal contraceptive, an intrauterine device (IUD), use of a double barrier method (condoms, sponge, diaphragm, or vaginal ring with spermicidal jellies or cream), or total abstinence during the study participation and for one month after last dose of study drug(s). 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.
  15. 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.
  16. 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 (see Exclusion #20).
  17. 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:

  18. Had surgery within 4 weeks prior to study treatment except for minor procedures (hepatic biliary stent placement is allowed)
  19. For Component 1 (PAC-1 alone), gliomas are excluded, as well as any history of brain metastases, seizures or underlying brain injury (e.g., traumatic brain injury, or hemorrhagic or ischemic stroke)
  20. Patients 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.
  21. Has a known hypersensitivity to temozolomide (this criterion applies only in Component 2)
  22. Has a history of blood clots, pulmonary embolism, or deep vein thrombosis unless controlled by anticoagulant treatment (patient must be on stable dose for 2 weeks)
  23. Has a history of an arterial thromboembolic event within the prior six months including cerebrovascular accident, transient ischemic attack, myocardial infarction, or unstable angina.
  24. Has uncontrolled human immunodeficiency virus (HIV) (defined as HIV RNA >500 copies/ml and CD4+ count<200/mm3 on antiretroviral therapy) infection or hepatitis B (defined as ALT > 1 x ULN, and HBV DNA >2000 IU/ml) or hepatitis C (defined as ALT > 1 x ULN, persistent viremia on antiviral therapy) infections.
  25. Has any clinically significant infection, i.e., any acute viral, bacterial, or fungal infection that requires specific treatment (anti-infective treatment has to be completed ≥ 7 days prior to study entry)
  26. Has any other severe, uncontrolled medical condition, including uncontrolled diabetes mellitus (defined as a Hemoglobin A1C≥ 9% in patients with a prior history of diabetes, 28 days prior to study ) or clinical signs of unstable congestive heart failure (Stage III-IV of the New York Heart Association Functional Classification) (Appendix 5).
  27. Radiation therapy to more than 25% of the bone marrow. Whole pelvic radiation is considered to be over 25%.
  28. Prior allogeneic bone marrow or organ transplantation.
  29. > Grade 1 peripheral neuropathy within 14 days before enrollment.
  30. Pregnant or breastfeeding - temozolomide is Pregnancy Category D - can cause fetal harm. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
  31. Patient has received other investigational drugs within 14 days prior to study treatment.
  32. Other severe acute or chronic medical or psychiatric conditions or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for enrollment in this study.
  33. 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).
  34. Presence of any non-healing wound, fracture, or ulcer within 28 days prior to the first dose of study drug.
  35. Has any condition that, in the opinion of the investigator, might jeopardize the safety of the patient or interfere with protocol compliance
  36. Has any mental or medical condition that prevents the patient from giving informed consent or participating in the trial
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03332355


Contacts
Contact: Ted Tarasow, PhD 510-219-6200 Ted.Tarasow@VanquishOncology.com
Contact: Harvey Arbit, Pharm.D. 651-454-3178 harvey@arbitconsulting.com

Locations
United States, Illinois
University of Illinois at Chicago Recruiting
Chicago, Illinois, United States, 60612
Contact: Oana C Danciu, M.D.         
United States, Maryland
Johns Hopkins Cancer Center Recruiting
Baltimore, Maryland, United States, 21231
Contact: Matthias Holdhoff, M.D.         
United States, Minnesota
Regions Hospital Recruiting
Saint Paul, Minnesota, United States, 55101
Contact: Richard Peterson, MD    651-254-3572    Richard.A.Peterson@HealthPartners.Com   
Principal Investigator: Richard Peterson, MD         
Sub-Investigator: Daniel Anderson, MD         
Sub-Investigator: Kurt Demel, MD         
Sub-Investigator: Randolph Hurley, MD         
Sub-Investigator: Balkrishna Jahagirdar, MD         
Sub-Investigator: Pryia Kumar, MD         
Sub-Investigator: Steven McCormack, MD         
Sub-Investigator: Gary Shapiro, MD         
Sub-Investigator: Peter Hurley, MD         
Sub-Investigator: Stephanie Kroon, PA-C         
Sub-Investigator: Angela Martizna, RN         
Sub-Investigator: Joanna Hill         
Sponsors and Collaborators
Vanquish Oncology, Inc.
University of Illinois at Chicago
Investigators
Principal Investigator: Oana C Danciu, M.D. Unversity of Illinois at Chicago
  More Information

Responsible Party: Vanquish Oncology, Inc.
ClinicalTrials.gov Identifier: NCT03332355     History of Changes
Other Study ID Numbers: 2017-0058
First Submitted: October 16, 2017
First Posted: November 6, 2017
Last Update Posted: November 7, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Vanquish Oncology, Inc.:
glioblastoma multiforme
anaplastic astrocytoma
high grade glioma
temozolomide
PROCASPASE ACTIVATING COMPOUND-1 (PAC-1)
advanced malignancy
maximal tolerated dose (MTD)

Additional relevant MeSH terms:
Neoplasms
Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Temozolomide
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents