GZ17-6.02 + Capecitabine for Metastatic Hormone Receptor Positive Breast Cancer

(GEN602 Trial)

Not currently recruiting at 3 trial locations

Overseen By MedInfo

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Genzada Pharmaceuticals USA, Inc.

Must not be taking: MAOIs, Class 1A/III antiarrhythmics

Disqualifiers: Cardiac disease, Active infections, CNS metastases, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 21-28 days per cycle

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called GZ17-6.02, both alone and with Capecitabine (a chemotherapy medication). It targets individuals with advanced solid tumors or lymphoma, and specific groups with metastatic breast or colorectal cancer. The trial aims to determine the safety and effectiveness of these oral treatments. Individuals with advanced cancer that has not responded to other treatments, specifically those diagnosed with hormone receptor-positive breast cancer or colorectal cancer, 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 protocol does not specify if you need to stop taking your current medications, but it mentions that you must discontinue any prohibited medications listed in Appendix 6. It's best to discuss your current medications with the trial team to ensure they are not on the prohibited list.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that capecitabine, one of the treatments tested in this trial, is generally well-tolerated by patients with advanced breast and colorectal cancer. Previous studies found capecitabine to be safe, even when combined with other drugs for treating advanced breast cancer. However, some patients might experience side effects like redness and swelling of the hands and feet (known as hand-foot syndrome) and diarrhea.

For GZ17-6.02, safety information is still being gathered because it is a newer drug. Early results suggest it may cause manageable side effects. This drug works in several ways to kill cancer cells, such as stressing the cells and cutting off their energy supply. Since the study is in an early phase, the full safety profile is still being learned, and more information will become available as research continues.

Anyone considering joining this trial should discuss the possible risks and benefits with their doctor to make an informed decision. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about GZ17-6.02 because it offers a fresh approach to treating metastatic hormone receptor-positive breast cancer. Unlike standard treatments, which often involve hormone therapies like tamoxifen or aromatase inhibitors, GZ17-6.02 introduces a novel mechanism of action by combining with Capecitabine, a chemotherapy drug, to potentially enhance its effectiveness. This combination may offer a more targeted attack on cancer cells, possibly improving outcomes for patients who have limited options. Additionally, GZ17-6.02 can be taken orally, providing a more convenient alternative to intravenous treatments.

What evidence suggests that this trial's treatments could be effective for metastatic hormone receptor positive breast cancer?

Research has shown that Capecitabine effectively treats hormone receptor-positive metastatic breast cancer, performing better in these cases than in hormone receptor-negative ones. This trial will test the combination of GZ17-6.02 with Capecitabine for metastatic hormone receptor-positive breast cancer in one arm and for metastatic colorectal cancer in another. Additionally, one arm will study GZ17-6.02 as a monotherapy. The new drug, GZ17-6.02, targets cancer cells by cutting off their energy supply and inducing cellular stress. Early studies combining GZ17-6.02 with other drugs have shown promise, particularly for challenging cases where other treatments have failed. ^{1 2 3 4 5}

Who Is on the Research Team?

Kathryn Gazarik

Principal Investigator

Translational Drug Development

Are You a Good Fit for This Trial?

Inclusion Criteria

Urinalysis: No clinically significant abnormalities

Patients with a pathologically confirmed diagnosis of advanced solid tumors or lymphoma

Albumin ≥ 3.0 g/dL within seven days of initiating protocol treatment

Exclusion Criteria

You are allergic or have had bad reactions to capecitabine or 5-FU.

You are currently taking any experimental medication.

You are currently taking medication called MAOIs.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive GZ17-6.02 monotherapy or in combination with Capecitabine on a 21-day or 28-day schedule

21-28 days per cycle

Regular visits as per cycle schedule

Dose Escalation

Determination of maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of GZ17-6.02

18 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Capecitabine
• GZ17-6.02

How Is the Trial Designed?

Group I: Experimental: monotherapy Experimental Treatment 1 Intervention

GZ17-6.02 given orally on a daily x 28 day schedule. This will be a dose escalation study.

Group II: Experimental: Combination with Capecitabine in Metastatic Hormone Receptor Positive Breast Cancer Experimental Treatment 2 Interventions

GZ17-6.02 given orally twice daily x 21 day schedule in combination with Capecitabine 825 mg/m2 orally twice daily for 14 days x 21 day schedule.

Group III: Experimental: Combination with Capecitabine in Metastatic Colorectal Cancer Experimental Treatment 2 Interventions

GZ17-6.02 given orally twice daily x 21 day schedule in combination with Capecitabine 850 mg/m2 orally twice daily for 14 days x 21 day schedule.

Who Is Running the Clinical Trial?

Genzada Pharmaceuticals USA, Inc.

Lead Sponsor

Trials

2

Recruited

170+

Translational Drug Development

Collaborator

Trials

19

Recruited

1,000+

Published Research Related to This Trial

In a study of 95 women aged 55 and older with advanced breast cancer, oral capecitabine showed a higher overall response rate of 30% compared to 16% for the intravenous CMF regimen, indicating its effectiveness as a first-line treatment.

Capecitabine was generally well tolerated, with fewer instances of alopecia and myelosuppression compared to CMF, although it did lead to more cases of diarrhea and hand-foot syndrome, which were manageable with dose adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, open-label, phase II trial of oral capecitabine (Xeloda) vs. a reference arm of intravenous CMF (cyclophosphamide, methotrexate and 5-fluorouracil) as first-line therapy for advanced/metastatic breast cancer. Oshaughnessy, JA., Blum, J., Moiseyenko, V., et al.[2022]

In a phase II study involving 47 women with HER2-positive metastatic breast cancer, the combination of capecitabine, vinorelbine, and trastuzumab resulted in a confirmed response rate of 67%, exceeding the threshold needed to consider the treatment promising.

The treatment also showed a median progression-free survival of 11.3 months and a median overall survival of 28.5 months, indicating significant efficacy for patients receiving this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II interventional study (N0337) of capecitabine in combination with vinorelbine and trastuzumab for first- or second-line treatment of HER2-positive metastatic breast cancer: a north central cancer treatment group trial. Tan, WW., Allred, JB., Salim, M., et al.[2021]

The study evaluated the combination of S-1 and T-DM1 in 13 patients with HER2-positive metastatic breast cancer, determining that S-1 can be safely administered at a maximum tolerable dose of 80 mg/m2/day alongside T-DM1 without significant dose-limiting toxicities.

One dose-limiting toxicity was observed at the lower dose level, but no severe adverse events occurred at the higher dose, suggesting that this combination treatment is a promising and safe option for patients previously treated with trastuzumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab Emtansine (T-DM1) Plus S-1 in Patients with Trastuzumab-Pretreated HER2-Positive Advanced or Metastatic Breast Cancer: A Phase Ib Study. Kojima, Y., Yoshie, R., Kawamoto, H., et al.[2019]

Capecitabine is a well-tolerated treatment for metastatic breast cancer, showing minimal side effects like myelosuppression and hair loss, which makes it a promising option for combination therapies with other anticancer drugs.

Ongoing phase II/III trials are investigating the use of capecitabine in early breast cancer treatment, and preliminary results indicate that it may provide significant benefits when used as part of adjuvant and neoadjuvant therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Future options with capecitabine (Xeloda) in (neo)adjuvant treatment of breast cancer. Fumoleau, P., Cameron, D.[2019]

A retrospective analysis of 141 patients with metastatic breast cancer found that starting capecitabine at a lower dose of 2000 mg/m2/day resulted in fewer severe toxic effects compared to the standard dose of 2500 mg/m2/day, while maintaining similar response rates.

The study suggests that individualizing the dose of capecitabine can improve tolerability without compromising efficacy, highlighting the need for further research through a phase III trial to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lower dose capecitabine has a more favorable therapeutic index in metastatic breast cancer: retrospective analysis of patients treated at M. D. Anderson Cancer Center and a review of capecitabine toxicity in the literature. Hennessy, BT., Gauthier, AM., Michaud, LB., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03775525

NCT03775525 | Study Evaluating GZ17-6.02 in Patients ... This Phase I/Ib study is a Multicenter, Open-label, Dose-Escalation, Safety, Pharmacodynamic and Pharmacokinetic Study of GZ17-6.02 Monotherapy and in ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8754587/

GZ17-6.02 and palbociclib interact to kill ER+ breast ... We first determined whether these drugs interacted with GZ17-6.02 to kill estrogen receptor positive breast cancer cells (Figure 1; Supplementary Figure 1).

3. withpower.com withpower.com/trial/phase-1-lymphoma-2-2019-d5947

GZ17-6.02 + Capecitabine for Metastatic Hormone ... In a study of 95 women aged 55 and older with advanced breast cancer, oral capecitabine showed a higher overall response rate of 30% compared to 16% for the ...

4. synapse.patsnap.com synapse.patsnap.com/drug/9be0e98e9935480a9556241d697a92bd

GZ17-6.02 - Drug Targets, Indications, Patents GZ17-6.02 reduced the expression of PD-L1 in uveal melanoma cells to a similar extent as observed in cutaneous melanoma cells whereas it was less effective at ...

5. delta.larvol.com delta.larvol.com/Products/?ProductId=ca29a786-753e-4fd0-af4a-6e292256dd38

GZ17-6.02 / Ionics Life Sci GZ17-6.02 is a multi-factorial killer, utilizing ER stress, macroautophagy, death receptor signaling and directly causing mitochondrial dysfunction.