LymphomaPhase 1NCT04827810
A Phase I Safety and Pharmacokinetic Study of Gamitrinib Administered Intravenously to Patients With Advanced Cancer
A Phase 1 study testing Gamitrinib in people with Lymphoma and Advanced Solid Tumor, run by Fox Chase Cancer Center at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lymphoma, Advanced Solid Tumor
- What is being tested?
- Gamitrinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Nov 2021to 30 Dec 2027
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 patients must have at least one site of measurable disease as defined by RECIST v. 1.1. or RECIL 2017, for solid tumors and lymphoma, respectively ii. Patients in the expansion cohort must have at least one non-target lesion deemed safe to biopsy, in the opinion of the investigator, and be willing to undergo mandatory core biopsies. This includes pre-treatment and an on-treatment biopsy. Biopsies at the time of progression are highly desired, but optional.
- The lesion(s) which will be used for response assessment may not be biopsied iv. Target lesions that have been previously irradiated will not be considered measurable unless increase in size is observed following completion of radiation therapy
- 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.
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- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
About this study
Official title: PH-139: A Phase I Safety and Pharmacokinetic Study of Gamitrinib Administered Intravenously to Patients With Advanced Cancer
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.
- Conditions
- Lymphoma, Advanced Solid Tumor
- Being tested
- Gamitrinib
- Medical subject headings
- Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GamitrinibDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Dose -1 | Experimental | Accelerated Phase: - Standard Phase: 5 mg Receives: Drug: Gamitrinib |
| Dose 1 | Experimental | Accelerated Phase: 10 mg Standard Phase: 10 mg Receives: Drug: Gamitrinib |
| Dose 2 | Experimental | Accelerated Phase: 20 mg Standard Phase: 20 mg Receives: Drug: Gamitrinib |
| Dose 3 | Experimental | Accelerated Phase: 40 mg Standard Phase: 35 mg Receives: Drug: Gamitrinib |
| Dose 4 | Experimental | Accelerated Phase: 80 mg Standard Phase: 50 mg Receives: Drug: Gamitrinib |
| Dose 5 | Experimental | Accelerated Phase: 160 mg Standard Phase: 65 mg Receives: Drug: Gamitrinib |
| Dose 6 | Experimental | Accelerated Phase: 320 mg Standard Phase: 85 mg Receives: Drug: Gamitrinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine the MTD and/or RP2D of gamitrinib when administered once weekly.
First cycle dose-limiting toxicities. The maximally tolerated dose (MTD) is defined as the dose level below which the absolute observed DLT rate is > 25%. The MTD is equivalent to the anticipated recommended phase 2 dose (RP2D).
Measured: 7 years
Secondary outcomes (8)
Evaluate the overall safety profile of intravenously administered single-agent gamitrinib
Overall, safety profile of gamitrinib as characterized by type, frequency, severity, timing and relationship to study therapy of adverse events and laboratory abnormalities according to NCI CTCAE v5.0.
Measured: 7 years
To evaluate the peak concentration (Cmax) of gamitrinib
Blood sample will be collected for determination of gamitrinib plasma concentrations. The PK parameter to be evaluated includes peak concentration (Cmax).
Measured: 7 years
To evaluate the area under the concentration time curve (AUC0-t) of gamitrinib
Blood sample will be collected for determination of gamitrinib plasma concentrations. PK parameter to be evaluated includes area under the concentration time curve (AUC0-t).
Measured: 7 years
To evaluate the clearance (CL) of gamitrinib
Blood sample will be collected for determination of gamitrinib plasma concentrations. PK parameter to be evaluated includes clearance (CL).
Measured: 7 years
To evaluate the time to maximum concentration (Tmax) of gamitrinib
Blood sample will be collected for determination of gamitrinib plasma concentrations. PK parameter to be evaluated includes time to maximum concentration (Tmax).
Measured: 7 years
To evaluate the coefficient of variation (CV) of gamitrinib
Blood sample will be collected for determination of gamitrinib plasma concentrations. A coefficient of variation (CV) will be assessed at each dose level.
Measured: 7 years
Assess the pharmacodynamic effects of gamitrinib
Assessment of gamitrinib effects on pharmacodynamic markers. The processed samples will be profiled for changes in the expression of 301 metabolites by Ultrahigh Performance Liquid Chromatography/Mass Spectrometry (UPLC/MS) or Gas Chromatography/Mass Spectrometry (G/MS) using the Metabolon, Inc. discovery platform
Measured: 7 years
Document any anti-tumor activity of single agent gamitrinib
Objective tumor response, as assessed using RECIST 1.1 and RECIL 2017 criteria
Measured: 7 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2021
- Study start5 Nov 2021
- Primary completion30 Jun 2027 (estimated)
- Study completion30 Dec 2027 (estimated)
Why it stopped: Pending amendment to open further Cohorts
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for LymphomaStudies of the same condition, open and under way.
- More trials run by Fox Chase Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 42 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fox Chase Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Cancer Institute (NCI)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04827810
- Sponsor's protocol ID
- 21-1045
- Other IDs
- 1R01CA225913-01A1
- Status last verified
- Sep 2026
- First submitted
- 29 Mar 2021
- Last updated
- 21 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Hayat U, Elliott GT, Olszanski AJ, Altieri DC. Feasibility and safety of targeting mitochondria for cancer therapy - preclinical characterization of gamitrinib, a first-in-class, mitochondriaL-targeted small molecule Hsp90 inhibitor. Cancer Biol Ther. 2022 Dec 31;23(1):117-126. doi: 10.1080/15384047.2022.2029132.
PubMed 35129069
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PH-139: A Phase I Safety and Pharmacokinetic Study of Gamitrinib Administered Intravenously to Patients With Advanced Cancer
- ClinicalTrials.gov ID
- NCT04827810
- Acronym / sponsor ID
- 21-1045
- Conditions
- Lymphoma, Advanced Solid Tumor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: Pending amendment to open further Cohorts
- Enrolment
- 42 participants (estimated)
- Lead sponsor
- Fox Chase Cancer CenterUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Cancer Institute (NCI)
- Study start
- 5 Nov 2021 (actual)
- Primary completion
- 30 Jun 2027 (estimated)
- Study completion
- 30 Dec 2027 (estimated)
- First posted
- 1 Apr 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Dose -1 | Experimental | Drug: GamitrinibAccelerated Phase: - Standard Phase: 5 mg |
| Dose 1 | Experimental | Drug: GamitrinibAccelerated Phase: 10 mg Standard Phase: 10 mg |
| Dose 2 | Experimental | Drug: GamitrinibAccelerated Phase: 20 mg Standard Phase: 20 mg |
| Dose 3 | Experimental | Drug: GamitrinibAccelerated Phase: 40 mg Standard Phase: 35 mg |
| Dose 4 | Experimental | Drug: GamitrinibAccelerated Phase: 80 mg Standard Phase: 50 mg |
| Dose 5 | Experimental | Drug: GamitrinibAccelerated Phase: 160 mg Standard Phase: 65 mg |
| Dose 6 | Experimental | Drug: GamitrinibAccelerated Phase: 320 mg Standard Phase: 85 mg |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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:
- The lesion(s) which will be used for response assessment may not be biopsied iv. Target lesions that have been previously irradiated will not be considered measurable unless increase in size is observed following completion of radiation therapy
- 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.
Key exclusion criteria (8 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GamitrinibThis 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. | Drug | Dose -1, Dose 1, Dose 2, Dose 3, Dose 4, Dose 5, Dose 6 |
Primary outcome
Determine the MTD and/or RP2D of gamitrinib when administered once weekly.
Time frame: 7 years
First cycle dose-limiting toxicities. The maximally tolerated dose (MTD) is defined as the dose level below which the absolute observed DLT rate is > 25%. The MTD is equivalent to the anticipated recommended phase 2 dose (RP2D).
8 secondary outcomes
Evaluate the overall safety profile of intravenously administered single-agent gamitrinib
Time frame: 7 years
To evaluate the peak concentration (Cmax) of gamitrinib
Time frame: 7 years
To evaluate the area under the concentration time curve (AUC0-t) of gamitrinib
Time frame: 7 years
To evaluate the clearance (CL) of gamitrinib
Time frame: 7 years
To evaluate the time to maximum concentration (Tmax) of gamitrinib
Time frame: 7 years
To evaluate the coefficient of variation (CV) of gamitrinib
Time frame: 7 years
Assess the pharmacodynamic effects of gamitrinib
Time frame: 7 years
Document any anti-tumor activity of single agent gamitrinib
Time frame: 7 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2026.
- Derived from this study: PubMed 35129069Hayat U, Elliott GT, Olszanski AJ, Altieri DC. Feasibility and safety of targeting mitochondria for cancer therapy - preclinical characterization of gamitrinib, a first-in-class, mitochondriaL-targeted small molecule Hsp90 inhibitor. Cancer Biol Ther. 2022 Dec 31;23(1):117-126. doi: 10.1080/15384047.2022.2029132.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Gamitrinib in people with Lymphoma and Advanced Solid Tumor, run by Fox Chase Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: paused, as of the sponsor's last update on 21 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determine the MTD and/or RP2D of gamitrinib when administered once weekly. (time frame: 7 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04827810, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2026.