Mocetinostat + Vinorelbine for Rhabdomyosarcoma

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial seeks to determine the safest and most effective dose of a new drug combination for treating rhabdomyosarcoma, a muscle cancer unresponsive to standard treatments. The combination includes mocetinostat, which may inhibit cancer cell growth, and vinorelbine, a chemotherapy drug that helps kill or slow cancer cells. The trial targets young people whose cancer has spread or recurred after treatment and cannot be treated with surgery. Those with rhabdomyosarcoma unresponsive to 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 therapy.

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.

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

Research has shown that the combination of mocetinostat and vinorelbine is promising in terms of safety. In a study involving patients with rhabdomyosarcoma, a type of cancer, this treatment was generally well-tolerated, with most patients not experiencing serious side effects.

The study included patients who had already tried other treatments. Despite their previous treatment experiences, the combination of mocetinostat and vinorelbine remained manageable, indicating that it does not add many extra side effects—a positive sign for safety.

Prospective trial participants can find reassurance in these early findings. The treatment appears safe enough to warrant further testing in clinical trials. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using Mocetinostat and Vinorelbine for rhabdomyosarcoma because this combination offers a novel approach to fighting the disease. Unlike conventional treatments such as chemotherapy, which broadly attack cancer cells, Mocetinostat is an HDAC inhibitor that targets specific enzymes involved in cancer cell growth and survival, potentially improving effectiveness and reducing side effects. Additionally, combining Mocetinostat with Vinorelbine, a chemotherapy drug, could enhance the overall treatment efficacy by attacking the cancer from multiple fronts, possibly leading to better outcomes for patients. This dual approach represents a significant advancement in personalized cancer therapy.

What evidence suggests that mocetinostat and vinorelbine might be an effective treatment for rhabdomyosarcoma?

Research has shown that combining mocetinostat with vinorelbine can help treat patients with rhabdomyosarcoma, particularly those unresponsive to other treatments. Mocetinostat blocks proteins that aid cancer cell growth, while vinorelbine kills cancer cells or prevents their spread. An early review of this combination found it effective and safe for patients who had tried multiple treatments. This trial will evaluate the effectiveness of mocetinostat and vinorelbine together, as early studies suggest this combination might be more effective than vinorelbine alone for this cancer type. ^{1 3 4 6 7}

Who Is on the Research Team?

Noah C. Federman, MD

Principal Investigator

University of California at Los Angeles

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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]

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]

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]

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]

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 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 (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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.11553

A phase 1 dose-escalation/expansion clinical trial of ... In this interim analysis, Mocetinostat plus vinorelbine shows high efficacy and acceptable safety profile in this heavily pretreated group of R/R RMS patients.

2. ucla.clinicaltrials.researcherprofiles.org ucla.clinicaltrials.researcherprofiles.org/trial/NCT04299113

Mocetinostat With Vinorelbine in Children, Adolescents ... Giving mocetinostat and vinorelbine may work better in treating children, adolescents, and young adults with rhabdomyosarcoma compared to vinorelbine alone.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7922213/

Relapsed Rhabdomyosarcoma - PMC - PubMed Central - NIH The other trial is a phase 1 study of the combination of vinorelbine and mocetinostat, a histone deacetylase (HDAC) inhibitor (NCT042991130).

4. researchgate.net researchgate.net/publication/361125136_A_phase_1_dose-escalationexpansion_clinical_trial_of_mocetinostat_in_combination_with_vinorelbine_in_adolescents_and_young_adults_with_refractory_andor_recurrent_rhabdomyosarcoma_Interim_results

A phase 1 dose-escalation/expansion clinical trial of ... New reports on the efficacy and good tolerance of the combination of vinorelbine with the histone deacetylase inhibitor mocetinostat in RMS is ...

5. withpower.com withpower.com/trial/phase-1-rhabdomyosarcoma-4-2020-7dfcb

Mocetinostat + Vinorelbine for Rhabdomyosarcoma 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 ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04299113?cond=cancer&term=Mocetinostat&rank=8

NCT04299113 | Mocetinostat With Vinorelbine in Children ... Giving mocetinostat and vinorelbine may work better in treating children, adolescents, and young adults with rhabdomyosarcoma compared to vinorelbine alone.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10519430/

Children's Oncology Group's 2023 Blueprint for Research The current COG HR-RMS study, ARST2031, compares 42 weeks of VAC or VAC with vinorelbine in a randomized manner, followed by 24 weeks of maintenance with ...