Mocetinostat + Vinorelbine for Rhabdomyosarcoma

Recruiting at 1 trial location

Overseen By Sandra Rodriguez

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Jonsson Comprehensive Cancer Center

Must not be taking: QTc prolonging drugs

Disqualifiers: Symptomatic brain metastases, active infections, others

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

Compensation: Varies

Number of Visits: 6

38 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I trial studies the side effects and best dose of mocetinostat when given together with vinorelbine to see how well it works in treating children, adolescents, and young adults with rhabdomyosarcoma that has spread to nearby tissues or lymph nodes and cannot be removed by surgery (locally advanced unresectable) or has spread to other places in the body (metastatic), and does not respond to treatment (refractory) or has come back (relapsed). Mocetinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as vinorelbine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving mocetinostat and vinorelbine may work better in treating children, adolescents, and young adults with rhabdomyosarcoma compared to vinorelbine alone.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it excludes those using medications that increase the risk of heart rhythm problems. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Vinorelbine for treating rhabdomyosarcoma?

Vinorelbine has shown effectiveness in treating various cancers like breast cancer and non-small cell lung cancer, with response rates up to 53% in advanced breast cancer. Although not directly studied for rhabdomyosarcoma, its success in other cancers suggests potential benefits. ^{1 2 3 4 5}

Is the combination of Mocetinostat and Vinorelbine safe for humans?

Vinorelbine (also known as Navelbine) has been used safely in treating various cancers, including lung and breast cancer. It is generally well-tolerated, but can cause some side effects like granulocytopenia (a drop in white blood cells) and skin issues if it leaks from the vein during administration. ^{2 5 6 7 8}

What makes the drug combination of Mocetinostat and Vinorelbine unique for treating rhabdomyosarcoma?

This treatment is unique because it combines Mocetinostat, a drug that may target specific cancer pathways, with Vinorelbine, which has shown effectiveness in treating relapsed rhabdomyosarcoma, particularly in alveolar rhabdomyosarcoma, a type that typically has poorer outcomes. Vinorelbine works by interfering with cell division, making it a promising option for difficult-to-treat cancers. ^{2 3 5 9 10}

Research Team

Noah C. Federman, MD

Principal Investigator

University of California at Los Angeles

Eligibility Criteria

This trial is for children, adolescents, and young adults with rhabdomyosarcoma that's advanced or returned after treatment. Participants need to have a certain level of hemoglobin, be able to follow the study plan, and give informed consent (with guardian consent if under 18). They should not be pregnant or breastfeeding and must agree to contraception measures.

Inclusion Criteria

I am not pregnant, breastfeeding, or planning to become pregnant and agree to use two forms of birth control during the study.

My platelet count is above 100,000 and I haven't had a transfusion in the last week.

My rhabdomyosarcoma is advanced, cannot be surgically removed, or has returned, and standard treatments have failed.

Exclusion Criteria

My heart's electrical cycle (QTc interval) is longer than usual.

I had cancer before, but it wasn't skin cancer or a completely removed in situ carcinoma in the last 3 years.

I have not fully recovered from recent surgery, except for procedures to place a central venous catheter or port.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Determine the first cycle dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and a biologically effective and recommended phase 2 dose (RP2D) of mocetinostat in combination with vinorelbine

21 days per cycle

3 visits per cycle (in-person)

Expansion Cohort

Determine progression-free survival (PFS) at the RP2D of mocetinostat in combination with vinorelbine

21 days per cycle

3 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Treatment Details

Interventions

• Mocetinostat
• Vinorelbine

Trial Overview The trial tests mocetinostat combined with vinorelbine in treating rhabdomyosarcoma. Mocetinostat may block enzymes needed for tumor growth while vinorelbine could stop cell division. The goal is to see if this combination works better than vinorelbine alone.

Participant Groups

Group I: Treatment (vinorelbine, mocetinostat) Experimental Treatment 2 Interventions

Participants receive mocetinostat in combination with vinorelbine

Who Is Running the Clinical Trial?

Jonsson Comprehensive Cancer Center

Lead Sponsor

Trials

373

Recruited

35,200+

Mirati Therapeutics Inc.

Industry Sponsor

Trials

73

Recruited

8,900+

Dr. Charles M. Baum

Mirati Therapeutics Inc.

Chief Executive Officer since 2023

MD, PhD

Dr. Joseph Leveque

Mirati Therapeutics Inc.

Chief Medical Officer since 2021

MD

Phase One Foundation

Collaborator

Trials

5

Recruited

180+

Findings from Research

Vinorelbine tartrate is an effective treatment for various solid tumors, particularly advanced non-small-cell lung cancer and metastatic breast cancer, with first-line response rates in breast cancer ranging from 40% to 44%.

When combined with other active drugs, vinorelbine can achieve response rates exceeding 50% in first-line therapy for breast cancer, indicating its potential as a key component in combination treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current status of vinorelbine for breast cancer. Smith, GA.[2018]

Vinorelbine (Navelbine) demonstrated an overall response rate of 16% in heavily pretreated patients with advanced and/or metastatic breast cancer, with responses primarily observed in lymph nodes, breast tissue, and soft tissue.

The treatment was well-tolerated, with the most significant toxicities being granulocytopenia and anemia, affecting 51% and 9% of patients respectively, while other side effects were mild and rare.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vinorelbine (navelbine) as a salvage treatment for advanced breast cancer. Degardin, M., Bonneterre, J., Hecquet, B., et al.[2020]

Vinorelbine (VNB) is an effective anti-tumor agent, particularly against non-small cell lung cancer and breast cancer, and can be used alone or in combination with other therapies like taxanes.

VNB works by targeting tubulin to disrupt microtubule formation, leading to cell cycle arrest in the G1 phase and inducing apoptosis in breast cancer cells through a mitochondrial pathway.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Apoptotic mechanisms induced in breast cancer cells by vinorelbine]. Nakajima, H., Sakaguchi, K., Mizuta, N., et al.[2018]

Vinorelbine (Navelbine) has shown significant antitumor activity in various cancers, including a 33% response rate in non-small cell lung cancer and a 53% response rate in advanced breast cancer, based on early phase II studies.

The drug primarily causes neutropenia as a side effect, with minimal neurotoxicity and manageable other side effects, making it a promising option for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in vinca-alkaloids: Navelbine. Marty, M., Extra, JM., Espie, M., et al.[2018]

Vinorelbine tartrate is an FDA-approved treatment for advanced, unresectable non-small cell lung cancer, known for its favorable safety profile and the ability to be administered weekly in an outpatient setting.

While approximately 40% of patients experience severe granulocytopenia, this side effect is quickly reversible, and only about 8% of patients need hospitalization for related complications, indicating that it can be managed effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vinorelbine tartrate: a promising new chemotherapeutic agent. Baldwin, PD.[2018]

Vinorelbine, an oral and intravenous chemotherapy drug, was found to have a maximum tolerated dose of 30 mg/m² in children without bone marrow involvement, with myelosuppression (reduced blood cell production) being the main side effect.

The study revealed that children metabolize vinorelbine differently than adults, showing higher plasma clearance and lower overall drug exposure, which may influence dosing strategies for pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I evaluation of oral and intravenous vinorelbine in pediatric cancer patients: a report from the Children's Oncology Group. Johansen, M., Kuttesch, J., Bleyer, WA., et al.[2018]

Vinorelbine tartrate is an effective treatment for advanced non-small cell lung cancer (NSCLC) and has shown comparable efficacy to combination therapies while causing less toxicity, making it a valuable option for patients.

The drug is generally well-tolerated with mostly mild to moderate side effects, such as leukopenia and granulocytopenia, which are reversible after stopping treatment, highlighting its safety profile for use in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vinorelbine tartrate (Navelbine): drug profile and nursing implications of a new vinca alkaloid. Brogden, JM., Nevidjon, B.[2018]

Vinorelbine tartrate is an effective first-line treatment for advanced non-small-cell lung cancer and is also used for advanced breast and ovarian cancers, as well as lymphoma.

The authors report two successful cases of treating skin necrosis caused by vinorelbine extravasation using hyaluronidase injections and saline flushout, highlighting the importance of early intervention in such incidents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two case reports of vinorelbine extravasation: management and review of the literature. Cicchetti, S., Jemec, B., Gault, DT.[2022]

A meta-analysis of five Phase 2 trials involving 156 patients with relapsed or refractory rhabdomyosarcoma (RMS) showed that vinorelbine significantly increased response rates in patients with alveolar rhabdomyosarcoma (ARMS) by 41% compared to those with embryonal rhabdomyosarcoma (ERMS).

Vinorelbine demonstrated efficacy as a treatment option for relapsed RMS, particularly in ARMS patients, suggesting it warrants further investigation for newly diagnosed cases, as there was no significant difference in disease progression rates between ARMS and ERMS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alveolar rhabdomyosarcoma has superior response rates to vinorelbine compared to embryonal rhabdomyosarcoma in patients with relapsed/refractory disease: A meta-analysis. Allen-Rhoades, W., Lupo, PJ., Scheurer, ME., et al.[2023]

The pilot study involving 18 patients aged 2-23 years demonstrated that the combination of vinorelbine and low-dose cyclophosphamide is feasible and shows activity against recurrent sarcomas, with one complete remission and six partial remissions observed.

Vinorelbine at a dose of 25 mg/m2 resulted in manageable toxicity, with 37% of cycles showing Grade 3 or higher neutropenia, while the recommended maintenance doses for future trials are cyclophosphamide 25 mg/m2 daily and vinorelbine 25 mg/m2 on specific days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vinorelbine and low-dose cyclophosphamide in the treatment of pediatric sarcomas: pilot study for the upcoming European Rhabdomyosarcoma Protocol. Casanova, M., Ferrari, A., Bisogno, G., et al.[2018]

References

1. United States pubmed.ncbi.nlm.nih.gov

Current status of vinorelbine for breast cancer. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Vinorelbine (navelbine) as a salvage treatment for advanced breast cancer. [2020]

3. Japan pubmed.ncbi.nlm.nih.gov

[Apoptotic mechanisms induced in breast cancer cells by vinorelbine]. [2018]

4. Germany pubmed.ncbi.nlm.nih.gov

Advances in vinca-alkaloids: Navelbine. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Vinorelbine tartrate: a promising new chemotherapeutic agent. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Phase I evaluation of oral and intravenous vinorelbine in pediatric cancer patients: a report from the Children's Oncology Group. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Vinorelbine tartrate (Navelbine): drug profile and nursing implications of a new vinca alkaloid. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Two case reports of vinorelbine extravasation: management and review of the literature. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Alveolar rhabdomyosarcoma has superior response rates to vinorelbine compared to embryonal rhabdomyosarcoma in patients with relapsed/refractory disease: A meta-analysis. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Vinorelbine and low-dose cyclophosphamide in the treatment of pediatric sarcomas: pilot study for the upcoming European Rhabdomyosarcoma Protocol. [2018]