Metronomic Therapy in Patients With Metastatic Melanoma

Metronomic Therapy in Patients With Metastatic Melanoma: A Phase II Study of Low Dose Vinblastine, Cyclophosphamide, and Dacarbazine

SUMMARY: Metronomic Therapy in Patients with Metastatic Melanoma: A Phase II Study of Low Dose Vinblastine, Cyclophosphamide, and Dacarbazine.

Patients with measurable metastatic melanoma are eligible. All patients will be treated as outlined below with combined vinblastine, cyclophosphamide, and dacarbazine. Patients will be treated continuously, until evidence of progression of disease, or for up to two cycles following disappearance of all disease. A cycle will be defined as three weeks of continuous therapy with a one week rest.

Study Overview

• Status: Terminated
• Conditions: Metastatic Melanoma
• Intervention / Treatment: Drug: vinblastine; Drug: Cyclophosphamide; Drug: dacarbazine

Detailed Description

Low dose continuous chemotherapy, called metronomic chemotherapy, is designed to target vascular cells and inhibit tumor growth and metastasises. A recent study in a melanoma mouse model has identified low dose vinblastine, cyclophosphamide and dacarbazine as a treatment which improves the animal's survival and is superior to full dose dacarbazine alone. This clinical trial seeks to translate this laboratory model directly into metastatic melanoma patients.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth-Hitchcock Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

• Metastatic melanoma with measurable disease
• Patients must be at least 4 weeks from their last immunotherapy, radiation, surgery or chemotherapy (6 weeks for nitrosoureas) and recovered from all ill
• Karnofsky Performance Status ≥60%
• Life expectancy ≥ twelve weeks
• Adequate end organ function
• Women should not be lactating and, if of childbearing age, have a negative pregnancy test within two weeks of entry to the study.
• Appropriate Contraception in both sexes
• The patient must be competent and signed informed consent.

EXCLUSION CRITERIA

• Concomitant second malignancy except for non-melanoma skin cancer, and non-invasive cancer such as cervical CIS, superficial bladder cancer without local recurrence, breast CIS.
• In patients with a prior history of invasive malignancy, less than five years in complete remission.
• Have evidence of significant co-morbid illness such as uncontrolled diabetes - Uncontrolled brain metastasis: Patients with brain metastasis most have been treated with brain radiation therapy or surgery and remain clinically stable for a minimum of 4 weeks.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Combined Low Dose Treatment; A cycle of therapy is 3 weeks of continuous dosing with a 1 week rest. Schema of treatment is: 1 mg/m2 vinblastine three times a week iv 60 mg/m2 cyclophosphamide by mouth 15 mg/m2 dacarbazine three times a week iv	Drug: vinblastine; 1 mg/m2 vinblastine given three times per week administered intravenously.; Other Names: Velban; Drug: Cyclophosphamide; 60 mg/m2 cyclophosphamide taken orally every day for 3 weeks with one week rest; Other Names: Cytoxan; Drug: dacarbazine; 15 mg/m2 dacarbazine given three times per week for 3 weeks with 1 week rest; Other Names: DTIC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	Tumor evaluation will be performed every 8 weeks from day 1 of cycle 1 (+/- 1 week) while on therapy assessed by RECIST 1.0 criteria.	From date of registration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Response Rate	To be assigned a status of partial response or complete response, changes in tumor measurements must be confirmed by repeat assessments that should be performed no less than 4 weeks after the criteria for response are first met. In the case of stable disease, follow-up measurements must have met the stable disease criteria at least once after study entry at a minimum interval (in general, not less than 6-8 weeks) that is defined in the study protocol	Tumor evaluation will be performed every 8 weeks from day1 of cycle 1 (+ 1 week) while on therapy, clinical response will be assessed no less than 4 weeks after response criteria met.

Collaborators and Investigators

• Sponsor: Dartmouth-Hitchcock Medical Center
• Investigators: Principal Investigator: Marc S. Ernstoff, MD, Dartmouth-Hitchcock Medical Center

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): January 1, 2013

Study Registration Dates

• First Submitted: January 17, 2012
• First Submitted That Met QC Criteria: February 24, 2012
• First Posted (Estimate): March 2, 2012

Study Record Updates

• Last Update Posted (Actual): January 15, 2019
• Last Update Submitted That Met QC Criteria: December 26, 2018
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Keywords: Cyclophosphamide; Vinblastine; Dacarbazine; Metastatic Melanoma; Metronomic Therapy
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Cyclophosphamide; Dacarbazine; Vinblastine
• Other Study ID Numbers: D1010; 22362 (Other Identifier: Committee for the Protection of Human Subjects)