Metronomic Therapy in Patients With Metastatic Melanoma

• Sponsor: Dartmouth-Hitchcock Medical Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01542255
• Collaborator: (none)
• Enrollment: 7
• Location: 1
• Arm: 1
• Duration (Months): 31
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Melanoma	Drug: vinblastine; Drug: Cyclophosphamide; Drug: dacarbazine	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 7 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Metronomic Therapy in Patients With Metastatic Melanoma: A Phase II Study of Low Dose Vinblastine, Cyclophosphamide, and Dacarbazine
• Study Start Date: Jun 1, 2010
• Actual Primary Completion Date: Jan 1, 2013
• Actual Study Completion Date: Jan 1, 2013

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Progression Free Survival [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]

   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.

Secondary Outcome Measures

1. Clinical Response Rate [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.]

   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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

• 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756

Sponsors and Collaborators

• Dartmouth-Hitchcock Medical Center

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Dartmouth-Hitchcock Medical Center
• ClinicalTrials.gov Identifier: NCT01542255
• Other Study ID Numbers: D1010; 22362
• First Posted: Mar 2, 2012
• Last Update Posted: Jan 15, 2019
• Last Verified: Sep 1, 2014

• Keywords provided by Dartmouth-Hitchcock Medical Center: Metronomic Therapy; Metastatic Melanoma; Vinblastine; Cyclophosphamide; Dacarbazine
• Additional relevant MeSH terms: Melanoma; Cyclophosphamide; Dacarbazine; Vinblastine

Study Results

Participant Flow

Recruitment Details	Enrolled from 6/2010 to 11/2012 at Dartmouth Hitichcock

Arm/Group Title	Combined Low Dose Treatment
Arm/Group Description	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 vinblastine: 1 mg/m2 vinblastine given three times per week administered intravenously. Cyclophosphamide: 60 mg/m2 cyclophosphamide taken orally every day for 3 weeks with one week rest dacarbazine: 15 mg/m2 dacarbazine given three times per week for 3 weeks with 1 week rest
Period Title: Overall Study
STARTED	7
Analyzed for Time to Progression	7
COMPLETED	7
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Combined Low Dose Treatment
Arm/Group Description	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 vinblastine: 1 mg/m2 vinblastine given three times per week administered intravenously. Cyclophosphamide: 60 mg/m2 cyclophosphamide taken orally every day for 3 weeks with one week rest dacarbazine: 15 mg/m2 dacarbazine given three times per week for 3 weeks with 1 week rest
Overall Participants	7
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	65
Sex: Female, Male (Count of Participants)
Female	1 14.3%
Male	6 85.7%
Region of Enrollment (participants) [Number]
United States	7 100%

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Single Arm
Arm/Group Description
Measure Participants	7
Median (Full Range) [weeks]	3

2. Secondary Outcome

Title	Clinical Response Rate
Description	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
Time Frame	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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Combined Low Dose Treatment
Arm/Group Description	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 vinblastine: 1 mg/m2 vinblastine given three times per week administered intravenously. Cyclophosphamide: 60 mg/m2 cyclophosphamide taken orally every day for 3 weeks with one week rest dacarbazine: 15 mg/m2 dacarbazine given three times per week for 3 weeks with 1 week rest
Measure Participants	7
Stable Disease	2 28.6%
Progressive Disease	5 71.4%

Adverse Events

Time Frame	Adverse events were collected for each subject from the time of start of treatment until 30 days after the last dose of treatment. As this study ended prematurely, adverse events were collected only for the seven subjects enrolled over a period of 1 year.
Arm/Group Title	Single Arm
Arm/Group Description	all patients received cyclophosphamide, DTIC and vinblastine
All Cause Mortality
	Single Arm
	Affected / at Risk (%)	# Events
Total	0/7 (0%)
Serious Adverse Events
	Single Arm
	Affected / at Risk (%)	# Events
Total	0/7 (0%)
Other (Not Including Serious) Adverse Events
	Single Arm
	Affected / at Risk (%)	# Events
Total	5/7 (71.4%)
Blood and lymphatic system disorders
Anemia	1/7 (14.3%)	1
Leukocytosis	1/7 (14.3%)	1
Cardiac disorders
Palpitations	1/7 (14.3%)	1
Eye disorders
Blurred vision	1/7 (14.3%)	1
Gastrointestinal disorders
constipation	2/7 (28.6%)	2
diarrhea	1/7 (14.3%)	1
Nausea	1/7 (14.3%)	1
Rectal hemorrhage	1/7 (14.3%)	1
Toothache	1/7 (14.3%)	1
General disorders
Edema - limbs	1/7 (14.3%)	1
Fatigue	1/7 (14.3%)	1
Injury, poisoning and procedural complications
Radiation recall reaction (dermatologic)	1/7 (14.3%)	1
Investigations
alanine aminotransferase increased	1/7 (14.3%)	4
Aspartate aminotransferase increased	1/7 (14.3%)	1
Creatinine increased	3/7 (42.9%)	3
Platelet count decreased	2/7 (28.6%)	7
Metabolism and nutrition disorders
Hypercalcemia	1/7 (14.3%)	1
Hyperglycemia	1/7 (14.3%)	1
Hyperkalemia	1/7 (14.3%)	1
Hypokalemia	2/7 (28.6%)	2
Musculoskeletal and connective tissue disorders
Muscle weakness	2/7 (28.6%)	2
Pain - extremity	2/7 (28.6%)	2
Nervous system disorders
Headache	2/7 (28.6%)	2
Ischemia cerebrovascular	1/7 (14.3%)	1
Memory impairment	1/7 (14.3%)	1
Tremor	1/7 (14.3%)	1
Psychiatric disorders
Mental status changes	1/7 (14.3%)	1
Renal and urinary disorders
Urinary incontinence	1/7 (14.3%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/7 (14.3%)	1
Skin and subcutaneous tissue disorders
alopecia	3/7 (42.9%)	3
Skin ulceration	1/7 (14.3%)	1

Limitations/Caveats

terminated early due to difficulty with scheduling three times per week office treatment

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.