RECRUITING

A Phase I Safety and Pharmacokinetic Study of Gamitrinib Administered Intravenously to Patients With Advanced Cancer

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This is a first-in-human, phase I, open-label, non-randomized dose-escalation and dose-expansion study with the primary objective to determine the safety profile of small molecule, mitochondrial-targeted Hsp90 inhibitor, gamitrinib, including identification of dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) in patients with advanced cancers. A secondary objective of the study is to determine the recommended dose and regimen(s) for a phase II study. This study is based on preclinical data demonstrating the anticancer activity, unique mechanism of action and preliminary safety of gamitrinib. In the dose-finding portion of this study, gamitrinib formulated in Lipoid S100®-based formulation will be administered as a 1-hour IV infusion once weekly for four weeks as 28-day treatment cycles. Up to 36 patients will be enrolled in the dose-escalation component of the study based on anticipated cohorts. The starting dose will be 10 mg, corresponding to allometric scaling) from the most sensitive species (rats) in the 29-day GLP toxicology and toxicokinetic studies with 14-day recovery period of gamitrinib. Dose-escalation will follow a 3+3 design. Six patients will be enrolled in the dose-expansion component of the study at MTD for the purpose of exploring pharmacodynamic effects via tumor pre and on-therapy biopsies.

Official Title

PH-139: A Phase I Safety and Pharmacokinetic Study of Gamitrinib Administered Intravenously to Patients With Advanced Cancer

Quick Facts

Study Start:2021-11-05

Study Completion:2026-12-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04827810

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Histologically confirmed diagnosis of advanced cancer refractory to standard of care therapy, or for whom no standard of care therapy is available. Any numbers of prior therapies are allowed. * Dose escalation phase: Solid tumors and lymphoma may have measurable or evaluable disease as per Response Evaluation Criteria in Solid Tumors (RECIST v. 1.1) or as per RECIL 2017 criteria * Dose expansion phase: * All previous therapies of cancer, including radiotherapy major surgery and investigational therapies must be discontinued for ≥14 days (≥ 28 days for mitomycin C or nitrosoureas) before Cycle 1 Day 1 (C1D1), and all acute effects of any prior therapy must have resolved to baseline severity or Grade ≤ 1 Common Terminology Criteria for Adverse Events (CTCAE v5), except alopecia or parameters defined in this eligibility list. * Age \> 18 years. * ECOG performance status 0- 2 * Patients must have normal organ and marrow function as defined below * Absolute neutrophil count ≥1,500/mm3 without growth factor use ≤ 7 days prior to C1D1 Platelets ≥85,000/mm3 without platelet transfusion ≤ 7 days prior to C1D1 Hemoglobin \>8.5 mg/dL without red blood cell transfusion ≤ 7 days prior to C1D1 Total serum bilirubin \<1.5 X upper limit of normal (ULN) (except for patients with documented Gilbert's syndrome) AST (SGOT)/ALT (SGPT) ≤2 X ULN; ≤ 5 X ULN if liver dysfunction is felt to be secondary to tumor burden Serum creatinine ≤ 1.5 X ULN (OR creatinine clearance ≥ 60 mL/min/1.73 m2) Serum or urine pregnancy test (WOCBP only) negative ≤7 days of C1D1 * Ability to understand and willingness to sign a written informed consent, HIPAA consent document and comply with the study scheduled visits, treatment plans, laboratory tests and other procedures. * Female patients must be surgically sterile or be postmenopausal, or must agree to use effective contraception during the period of the trial and for at least 90 days after completion of treatment. Male patients must be surgically sterile or must agree to use effective contraception during the period of the trial and for at least 90 days after completion of treatment. The decision of effective contraception will be based on the judgment of the principal investigator or a designated associate.	* Patients with symptomatic brain metastases are excluded. Patients with asymptomatic and treated CNS metastases may participate in this trial. The patient must have completed any prior treatment for CNS metastases \> 28 days prior to study entry, including radiotherapy or surgery. Concurrent use of steroids for the treatment of brain metastasis are not permitted. * Current treatment on another (therapeutic) clinical trial * Hypertension not adequately controlled with medications (\>150/100 mm Hg despite optimal medical therapy) * Active bacterial fungal or viral infection including hepatitis B (HBV), hepatitis C (HCV), requiring treatment with IV antibiotic, IV anti-fungal, or anti-viral (Testing is not required for eligibility). * Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness (testing is not required for eligibility). * Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack or symptomatic pulmonary embolism. * Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, or in the judgment of the investigator would make the patient inappropriate for entry into the study * Pregnant or breast feeding. Refer to section 4.4 for further detail.

Inclusion Criteria

Exclusion Criteria

* Histologically confirmed diagnosis of advanced cancer refractory to standard of care therapy, or for whom no standard of care therapy is available. Any numbers of prior therapies are allowed.
* Dose escalation phase: Solid tumors and lymphoma may have measurable or evaluable disease as per Response Evaluation Criteria in Solid Tumors (RECIST v. 1.1) or as per RECIL 2017 criteria
* Dose expansion phase:
* All previous therapies of cancer, including radiotherapy major surgery and investigational therapies must be discontinued for ≥14 days (≥ 28 days for mitomycin C or nitrosoureas) before Cycle 1 Day 1 (C1D1), and all acute effects of any prior therapy must have resolved to baseline severity or Grade ≤ 1 Common Terminology Criteria for Adverse Events (CTCAE v5), except alopecia or parameters defined in this eligibility list.
* Age \> 18 years.
* ECOG performance status 0- 2
* Patients must have normal organ and marrow function as defined below
* Absolute neutrophil count ≥1,500/mm3 without growth factor use ≤ 7 days prior to C1D1 Platelets ≥85,000/mm3 without platelet transfusion ≤ 7 days prior to C1D1 Hemoglobin \>8.5 mg/dL without red blood cell transfusion ≤ 7 days prior to C1D1 Total serum bilirubin \<1.5 X upper limit of normal (ULN) (except for patients with documented Gilbert's syndrome) AST (SGOT)/ALT (SGPT) ≤2 X ULN; ≤ 5 X ULN if liver dysfunction is felt to be secondary to tumor burden Serum creatinine ≤ 1.5 X ULN (OR creatinine clearance ≥ 60 mL/min/1.73 m2) Serum or urine pregnancy test (WOCBP only) negative ≤7 days of C1D1
* Ability to understand and willingness to sign a written informed consent, HIPAA consent document and comply with the study scheduled visits, treatment plans, laboratory tests and other procedures.
* Female patients must be surgically sterile or be postmenopausal, or must agree to use effective contraception during the period of the trial and for at least 90 days after completion of treatment. Male patients must be surgically sterile or must agree to use effective contraception during the period of the trial and for at least 90 days after completion of treatment. The decision of effective contraception will be based on the judgment of the principal investigator or a designated associate.

* Patients with symptomatic brain metastases are excluded. Patients with asymptomatic and treated CNS metastases may participate in this trial. The patient must have completed any prior treatment for CNS metastases \> 28 days prior to study entry, including radiotherapy or surgery. Concurrent use of steroids for the treatment of brain metastasis are not permitted.
* Current treatment on another (therapeutic) clinical trial
* Hypertension not adequately controlled with medications (\>150/100 mm Hg despite optimal medical therapy)
* Active bacterial fungal or viral infection including hepatitis B (HBV), hepatitis C (HCV), requiring treatment with IV antibiotic, IV anti-fungal, or anti-viral (Testing is not required for eligibility).
* Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness (testing is not required for eligibility).
* Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack or symptomatic pulmonary embolism.
* Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, or in the judgment of the investigator would make the patient inappropriate for entry into the study
* Pregnant or breast feeding. Refer to section 4.4 for further detail.

Contacts and Locations

Study Contact

Anthony Olszanski, MD

CONTACT

215-728-5673

Anthony.Olszanksi@fccc.edu

Matthew Zibelman, MD

CONTACT

215-728-3889

Matthew.Zibelman@fccc.edu

Study Locations (Sites)

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111

United States

Collaborators and Investigators

Sponsor: Fox Chase Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-11-05

Study Completion Date2026-12-30

Study Record Updates

Study Start Date2021-11-05

Study Completion Date2026-12-30

Terms related to this study

Additional Relevant MeSH Terms

Lymphoma
Advanced Solid Tumor