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

NCT02355535 | Completed Phase 1 DMC

• 1 other identifier: 2015-0057
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Solid Tumor; Pancreatic Neuroendocrine Tumor; Neuroendocrine Tumors

Keywords

refractory; intolerant; solid tumors; PNET; neuroendocrine

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose

  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.

  Up to 30 days post last dose

Secondary Outcomes (3)

• Adverse Effects

  Up to 30 days post final dose

• Disease Response based on RECIST Criteria for patients with solid tumors

  Up to 8 weeks following final dose

• Disease Response based on Deauville PET Criteria for patients with lymphoma

  Up to 8 weeks following final dose

Study Arms (1)

Open label

EXPERIMENTAL

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

Drug: PAC-1

Interventions

PAC-1 DRUG

PAC-1 is taken orally on days 1-21 of a 28-day cycle.

Also known as: Procaspase Activating Compound-1

Open label

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female ≥ 18 years of age
• Diagnosis of advanced solid tumor or hematologic malignancy (limited to lymphoma) that has failed or become intolerant to standard therapy
• 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
• Has an ECOG PS of 0, 1, or 2
• 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
• Has serum creatinine \< 1.5 × ULN
• Has hemoglobin ≥ 10 g/dL, ANC ≥ 1.5 × 109/L, and platelet count ≥ 100 × 109/L
• 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
• Must be willing and able to comply with study
• Has read, understood, and signed the ICF
• 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
• 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
• 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
• Willingness to donate blood for biomarker studies related to the type of therapies used in this trial and the tumor types being treated

You may not qualify if:

• Had surgery within 4 weeks prior to study treatment except for minor procedures (hepatic biliary stent placement is allowed)
• Gliomas are excluded, as well as any history of brain metastases, seizures or underlying brain injury
• 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.
• Has a history of blood clots, pulmonary embolism, or DVT unless controlled by anticoagulant treatment
• Has a history of an arterial thromboembolic event within the prior six months including CVA, TIA, MI, or unstable angina
• Has uncontrolled HIV or hepatitis B or C
• Has any clinically significant infection
• Has any other severe, uncontrolled medical condition, including uncontrolled DM or unstable CHF
• Radiation therapy to more than 25% of the bone marrow
• Prior allogeneic bone marrow or organ transplantation
• \> Grade 1 peripheral neuropathy within 14 days before enrollment.
• Patient has received other investigational drugs with 14 days before enrollment
• Other severe acute or chronic medical or psychiatric conditions or laboratory abnormality that may increase the risk associated with study participation
• 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)
• Presence of any non-healing wound, fracture, or ulcer

Sponsors & Collaborators

• Vanquish Oncology, Inc.: lead
• University of Illinois at Chicago: collaborator

Study Sites (3)

University of Illinois at Chicago

Chicago, Illinois, 60612, United States

Location

Johns Hopkins Kimmel Cancer Center

Baltimore, Maryland, 21231, United States

Location

Regions Hospital

Saint Paul, Minnesota, 55101, United States

Location

Related Publications (1)

• Danciu OC, Holdhoff M, Peterson RA, Fischer JH, Liu LC, Wang H, Venepalli NK, Chowdhery R, Nicholas MK, Russell MJ, Fan TM, Hergenrother PJ, Tarasow TM, Dudek AZ. Phase I study of procaspase-activating compound-1 (PAC-1) in the treatment of advanced malignancies. Br J Cancer. 2023 Mar;128(5):783-792. doi: 10.1038/s41416-022-02089-7. Epub 2022 Dec 5.

  PMID: 36470974 DERIVED

MeSH Terms

Conditions

Adenoma, Islet Cell; Neuroendocrine Tumors; Neuroectodermal Tumors, Primitive

Condition Hierarchy (Ancestors)

Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Pancreatic Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neoplasms, Neuroepithelial

Study Officials

• Oana C Danciu, M.D.

  University of Illinois at Chicago

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: January 30, 2015
• First Posted: February 4, 2015
• Study Start: February 1, 2015
• Primary Completion: May 18, 2020
• Study Completion: May 18, 2020
• Last Updated: September 24, 2020

Record last verified: 2020-09

Locations

US (3)