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

Solid Tumor Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02355535
• Other study ID #: 2015-0057
• Status: Completed
• Phase: Phase 1
• Start date: February 2015
• Est. completion date: May 18, 2020

Study information

• Verified date: September 2020
• Source: Vanquish Oncology, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: May 18, 2020
• Est. primary completion date: May 18, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Neoplasms
• Neuroendocrine Tumors
• Pancreatic Neuroendocrine Tumor
• Solid Tumor

Intervention

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

Locations

Country	Name	City	State
United States	Johns Hopkins Kimmel Cancer Center	Baltimore	Maryland
United States	University of Illinois at Chicago	Chicago	Illinois
United States	Regions Hospital	Saint Paul	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Vanquish Oncology, Inc.	University of Illinois at Chicago

Country where clinical trial is conducted

United States, 

Outcome

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