Gamitrinib for Cancer

Overseen By Matthew Zibelman, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Fox Chase Cancer Center

Must not be taking: Steroids

Disqualifiers: Symptomatic brain metastases, Hypertension, Infections, HIV/AIDS, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

42 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the safety of a new cancer treatment called gamitrinib. Researchers seek to determine the optimal dose for treating advanced cancers, particularly those unresponsive to standard treatments. Participants will receive an intravenous infusion of gamitrinib once a week for four weeks. Individuals with advanced cancer who have not found success with other treatments might be suitable candidates. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I need to stop my current medications to join the trial?

The trial requires that all previous cancer therapies, including radiotherapy and major surgery, be stopped for at least 14 days before starting the study treatment. However, the protocol does not specify if you need to stop other non-cancer medications, so it's best to discuss this with the trial team.

Is there any evidence suggesting that gamitrinib is likely to be safe for humans?

Research has shown that gamitrinib, a new cancer treatment, holds promise in early lab studies. These studies suggest it can kill cancer cells without harming important liver enzymes or other critical functions, indicating potential safety at certain doses. However, this trial is in its first phase, focusing on understanding safety and determining the right dose. At this stage, the treatment is being tested in humans for the first time, so unknown side effects may occur.

The trial will closely monitor participants to identify any safety issues that prevent dose escalation and to determine the highest dose that does not cause unacceptable side effects. This careful approach is common in early trials to ensure safety before assessing efficacy. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Gamitrinib is unique because it targets the mitochondria within cancer cells, disrupting their energy production and survival mechanisms. This is different from most current cancer treatments like chemotherapy and targeted therapies, which often focus on DNA or protein targets within the cell. Researchers are excited about Gamitrinib because its novel mechanism may overcome resistance to traditional treatments and could potentially be effective against a wide range of cancers. Additionally, by specifically targeting cancer cell mitochondria, Gamitrinib might offer a treatment option with fewer side effects on healthy cells.

What evidence suggests that gamitrinib might be an effective treatment for cancer?

Research has shown that gamitrinib, a new cancer treatment under study in this trial, appears promising based on lab studies. It slowed tumor growth and extended the lifespan of mice. This treatment targets a protein called Hsp90 in cancer cells, which aids their survival. By blocking this protein in the mitochondria (the cell's energy center), gamitrinib causes cancer cells to die. Early results suggest it could be effective for various cancers, including prostate cancer and acute myeloid leukemia. Although these findings come from early studies, they offer hope for its potential in treating cancer in humans. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults with advanced cancers, including solid tumors and lymphoma, that are resistant to standard treatments or have no standard options left. Participants must have measurable disease, normal organ/marrow function, and be willing to undergo biopsies. They should not have had cancer therapy within the last 14 days (28 for certain drugs) and must be in a stable condition with an ECOG performance status of 0-2.

Inclusion Criteria

I am older than 18 years.

I am able to care for myself and perform daily activities.

I am using or will use effective birth control during and after the trial as required.

Exclusion Criteria

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.

Current treatment on another (therapeutic) clinical trial

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-Escalation Treatment

Gamitrinib is administered as a 1-hour IV infusion once weekly for four weeks in 28-day treatment cycles to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT).

4 weeks per cycle

Weekly visits for infusion

Dose-Expansion Treatment

Six patients are enrolled at the MTD to explore pharmacodynamic effects via tumor biopsies.

4 weeks per cycle

Weekly visits for infusion and biopsies

Follow-up

Participants are monitored for safety and effectiveness after treatment, including pharmacokinetic and pharmacodynamic assessments.

7 years

What Are the Treatments Tested in This Trial?

Interventions

• Gamitrinib

Trial Overview The study tests Gamitrinib, a new drug targeting cancer cell mitochondria. It's given through IV once weekly over four weeks per cycle. The trial aims to find the safest dose without severe side effects (dose-limiting toxicities) and establish the maximum tolerated dose for future phase II studies.

How Is the Trial Designed?

Group I: Dose 6 Experimental Treatment 1 Intervention

Accelerated Phase: 320 mg Standard Phase: 85 mg

Group II: Dose 5 Experimental Treatment 1 Intervention

Accelerated Phase: 160 mg Standard Phase: 65 mg

Group III: Dose 4 Experimental Treatment 1 Intervention

Accelerated Phase: 80 mg Standard Phase: 50 mg

Group IV: Dose 3 Experimental Treatment 1 Intervention

Accelerated Phase: 40 mg Standard Phase: 35 mg

Group V: Dose 2 Experimental Treatment 1 Intervention

Accelerated Phase: 20 mg Standard Phase: 20 mg

Group VI: Dose 1 Experimental Treatment 1 Intervention

Accelerated Phase: 10 mg Standard Phase: 10 mg

Group VII: Dose -1 Experimental Treatment 1 Intervention

Accelerated Phase: - Standard Phase: 5 mg

Who Is Running the Clinical Trial?

Fox Chase Cancer Center

Lead Sponsor

Trials

236

Recruited

39,300+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9757132/

Antitumor Activity of a Mitochondrial-Targeted HSP90 Inhibitor ... Importantly, Gamitrinib significantly delayed the tumor growth and improved survival of mice in both CDX and PDX models in which tumors were either ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8820820/

preclinical characterization of gamitrinib, a first-in-class ... Gamitrinib IC50 for hERG conductance in patch-clamp studies (3.5 µM) was up to 20-fold times higher than the IC50 of inhibition of tumor growth ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04827810

A Phase I Safety and Pharmacokinetic Study of Gamitrinib ... 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 ...

4. aacrjournals.org aacrjournals.org/clincancerres/article/16/19/4779/75467/Preclinical-Characterization-of-Mitochondria

Preclinical Characterization of Mitochondria-Targeted Small ... In summary, the preclinical data reported here identify gamitrinibs (16) as promising anticancer agents for advanced prostate cancer in vivo. Although Hsp90 has ...

5. oncotarget.com oncotarget.com/article/23097/text/

A Mitochondrial-targeted purine-based HSP90 antagonist ... Similar results were obtained with Gamitrinib treatment of a panel of AML cell types, which also resulted in hallmarks of apoptosis, including ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35129069/

Feasibility and safety of targeting mitochondria for cancer ... Concentrations of Gamitrinib that trigger tumor cell killing (IC50 ~1-4 µM) do not affect cytochrome P450 isoforms CYP1A2, CYP2A6, CYP2B6, CYP2C8 or ion channel ...

7. tandfonline.com tandfonline.com/doi/full/10.1080/15384047.2022.2029132

Full article: Feasibility and safety of targeting mitochondria ... Here, we report on the preclinical characterization of Gamitrinib (GA mitochondrial matrix inhibitor), a first-in-class anticancer agent that couples the Heat ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S1355814524000774

An update on the status of HSP90 inhibitors in cancer ... To date, a total of 22 HSP90 inhibitors (HSP90i) have been tested in 186 cancer clinical trials, as reported by clinicaltrials.gov.