Mocetinostat + Vinorelbine for Rhabdomyosarcoma
Recruiting in Palo Alto (17 mi)
+1 other location
Overseen byNoah C. Federman, MD
Age: Any Age
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Jonsson Comprehensive Cancer Center
Must not be taking: QTc prolonging drugs
Disqualifiers: Symptomatic brain metastases, active infections, others
No Placebo Group
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.
12345Is 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.
25678What 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.
235910Eligibility 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.
+19 more
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.
+8 more
Trial 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
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: Treatment (vinorelbine, mocetinostat)Experimental Treatment2 Interventions
Participants receive mocetinostat in combination with vinorelbine
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
UCLA / Jonsson Comprehensive Cancer CenterLos Angeles, CA
Rebecca PhelanLos Angeles, CA
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Who Is Running the Clinical Trial?
Jonsson Comprehensive Cancer CenterLead Sponsor
Mirati Therapeutics Inc.Industry Sponsor
Phase One FoundationCollaborator
References
Current status of vinorelbine for breast cancer. [2018]Vinorelbine tartrate (Navelbine) is a new semisynthetic vinca alkaloid with efficacy against a variety of solid tumors, including non-small-cell lung cancer, breast cancer, head and neck cancer, and Hodgkin's lymphoma. Recently approved by the FDA for the first-line treatment of advanced non-small-cell lung cancer, vinorelbine is also under review by the FDA for use in patients with metastatic breast cancer. There is now extensive data confirming the activity of vinorelbine in metastatic breast cancer, with second-line response rates of 17% to 36% and first-line response rates of 40% to 44%. Investigators have combined vinorelbine with other active drugs against breast cancer to produce response rates exceeding 50% for first-line therapy. Numerous centers are now conducting randomized trials comparing vinorelbine to established second-line therapies for advanced breast cancer, such as paclitaxel (Taxol). Future research is needed to further define the precise role of vinorelbine as a component of combination therapy for metastatic breast cancer.
Vinorelbine (navelbine) as a salvage treatment for advanced breast cancer. [2020]Vinorelbine (Navelbine), a new vinca alkaloid, is an effective drug in breast cancer. Our study was undertaken to assess the efficacy and tolerance of Navelbine in refractory advanced and/or metastatic breast cancer (AMBC).
[Apoptotic mechanisms induced in breast cancer cells by vinorelbine]. [2018]Vinorelbine (VNB) is one of new semi-synthesized vinka alkaloids developed in France, of which anti-tumor activity is susceptible mainly to non-small cell lung cancer and breast cancer. Moreover, its clinical efficacy has been noted from single-agent therapy or combination therapy with taxanes. It is assumed that VNB selectively acts on tubulin which elaborates microtubules, strands the cells at G 1 phase and interferes with the mitosis. VNB has unique anti-tumor activity as an antimicrotubule agent and is expected to be available for treatment of multi-drug resistant tumors. In this report, we demonstrate that VNB, as an antimicrotubule agent, induces apoptosis in breast cancer cell line, MX-1 via a mitochondrial pathway.
Advances in vinca-alkaloids: Navelbine. [2018]Vinorelbine (Navelbine) is a new semisynthetic vinca alkaloid which chemically differs from vinblastine by substitutions on the catharantine moiety of the molecule. It has shown promising experimental antitumor activity against experimental murine tumors as well as continuous cell lines of human neoplastic origin and human tumor xenografts in nude mice. Acute subacute and chronic toxicity extensively studied in rodents, dogs and primate has shown that hematotoxicity was almost the sole side-effect; neurotoxicity appears very limited. Almost exclusive affinity of NVB for mitotic tubulin and tubulin associated protein accounts for this pattern of toxicity. Phase I and II studies have been conducted in humans. Dose limiting side-effect appears to be neutropenia: the drug is slightly emetogenic, induces little alopecia, almost no neurotoxicity, and no other toxicity. Although preliminary, results of phase II studies already suggest significant activity of NVB in non small lung cancer (33% response rate in 78 evaluable patients), advanced breast cancer (53% response rate in 33 pts without significant chemotherapy for the target progression) and Hodgkin's disease (90% response rate after 4 weekly courses in 31 pts). Thus extensive pharmacological studies and ongoing clinical studies confirm that chemical modifications of the catharantine moiety of vinca alcaloid can lead to active agents with broader spectrum of activity and easily manageable side effects.
Vinorelbine tartrate: a promising new chemotherapeutic agent. [2018]Vinorelbine tartrate (Navelbine, Burroughs Wellcome Company, Research Park, NC) is a semisynthetic analog of vinblastine that has been approved by the Food and Drug Administration for use in the treatment of advanced, unresectable non-small cell lung cancer. It has a favorable safety profile and can safely and easily be administered in the outpatient setting on a weekly basis. The major toxicity is severe, granulocytopenia (absolute neutrophil count
Phase I evaluation of oral and intravenous vinorelbine in pediatric cancer patients: a report from the Children's Oncology Group. [2018]Vinorelbine (Navelbine) is an orally absorbable Vinca with broad antitumor activity. It differs from other Vinca in that it is structurally modified on the catharanthine nucleus and has differential actions on tubulin that render it less neurotoxic than other compounds in this class. We conducted a phase I study of vinorelbine given the activity of Vinca alkaloids in many pediatric tumors.
Vinorelbine tartrate (Navelbine): drug profile and nursing implications of a new vinca alkaloid. [2018]To review the drug profile and nursing implications of a new vinca alkaloid, vinorelbine tartrate (Navelbine, Burroughs Wellcome Co., Research Triangle Park, NC).
Two case reports of vinorelbine extravasation: management and review of the literature. [2022]Vinorelbine tartrate (Navelbine, Burroughs Wellcome Company, Research Triangle Park, NC, USA) is a semisynthetic vinca alkaloid approved in many countries for the first-line treatment of patients with advanced non-small-cell lung cancer. It is also used in the treatment of advanced breast and ovarian cancers and lymphoma. Like other vinca alkaloids, Navelbine can cause skin necrosis as a consequence of inadvertent extravasation in surrounding tissues during intravenous administration. In such cases, early treatment is strongly advocated. There is no documented case of vinorelbine extravasation in the literature. The authors herein report two cases successfully treated with hyaluronidase injections plus saline flushout under local anesthesia.
Alveolar rhabdomyosarcoma has superior response rates to vinorelbine compared to embryonal rhabdomyosarcoma in patients with relapsed/refractory disease: A meta-analysis. [2023]Patients with alveolar rhabdomyosarcoma (ARMS) have inferior outcomes compared to patients with embryonal rhabdomyosarcoma (ERMS) and more effective chemotherapy options are needed for these patients. Vinorelbine is a semisynthetic vinca alkaloid that has clinical activity in relapsed rhabdomyosarcoma (RMS) when used alone or in combination with cyclophosphamide.
Vinorelbine and low-dose cyclophosphamide in the treatment of pediatric sarcomas: pilot study for the upcoming European Rhabdomyosarcoma Protocol. [2018]Following their previous report on the activity of vinorelbine in the treatment of rhabdomyosarcoma, the authors report the results of a pilot study aimed at defining the optimal dose of vinorelbine when this agent is used in conjunction with continuous, orally administered low-dose cyclophosphamide to treat patients with refractory or recurrent sarcoma. It is hoped that the combination of vinorelbine and low-dose cyclophosphamide can be used as a maintenance regimen in an upcoming European trial involving high-risk patients with rhabdomyosarcoma.