SARC018: A Study of Mocetinostat and Gemcitabine in Patients With Metastatic Leiomyosarcoma

• Sponsor: Sarcoma Alliance for Research through Collaboration (Other)
• Overall Status: Completed
• CT.gov ID: NCT02303262
• Collaborator: (none)
• Enrollment: 20
• Locations: 5
• Arm: 1
• Actual Duration (Months): 12.6
• Patients Per Site: 4
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This is an open-label, multi-center, Phase II trial studying the combination of mocetinostat and gemcitabine in patients who have previously demonstrated disease progression either while, or within six months after, receiving chemotherapy with a gemcitabine-based regimen.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Leiomyosarcoma	Drug: Mocetinostat; Drug: Gemcitabine	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Mocetinostat Administered With Gemcitabine for Patients With Metastatic Leiomyosarcoma With Progression or Relapse Following Prior Treatment With Gemcitabine-Containing Therapy
• Actual Study Start Date: Nov 12, 2015
• Actual Primary Completion Date: Dec 1, 2016
• Actual Study Completion Date: Dec 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Mocetinostat and gemcitabine For each 21-day cycle, gemcitabine is administered on days 5 and 12 and mocetinostat is administered 3 days a week.	Drug: Mocetinostat; Mocetinostat is taken orally at 70 mg/dose, 3 days per week, during cycle 1. Dose is increased to 90 mg starting at cycle 2.; Drug: Gemcitabine; Gemcitabine is administered via intravenous infusion at 1,000 mg/m2 at a rate of approximately 10 mg/m2/minute, on days 5 and 12 of every cycle.

Outcome Measures

Primary Outcome Measures

1. Response Rate (Per RECIST 1.1) [27 months]

   Response rate (CR or PR) will be calculated by the number of patients achieving a response divided by the number of patients having been evaluated for response. Per Response Evaluation Criteria in Solid Tumors (RECIST): Complete Response (CR) is the disappearance of all target lesions; Partial Response (PR) is at least a 30% decrease in the sum of longest diameters of all target lesions.

Secondary Outcome Measures

1. Duration of Response [27 months]

   The duration of objective response will be measured from the time measurement criteria are first met until disease progression is objectively documented.

2. Progression Free Survival (PFS) [27 months]

   Progression free survival is defined as the time from treatment initiation to the earlier date of assessment of objective progression or death by any cause in the absence of progression. Progression Free Survival (PFS) is defined as the time from treatment initiation to the earlier date of assessment of objective progression or death by any cause in the absence of progression. Progression will be assessed by RECIST v. 1.1.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Age ≥ 18 years

• Histologically documented leiomyosarcoma

• Prior systemic therapy with a gemcitabine containing regimen

• ECOG Performance Status of ≤ 1

• Measurable metastatic disease with a target lesion that has increased in size by 20% in maximal dimension either during or within six months after treatment with chemotherapy using a gemcitabine containing regimen

• Adequate organ function within 14 days of study entry

• Patients or their legal representative must be able to read (or have read to them), understand, and sign a written informed consent (approved by the institutional review board) within 14 days prior to start of treatment.

Exclusion Criteria:

• Concurrent, clinically significant, active malignancies (excluding basal cell carcinoma or cervical intraepithelial neoplasia [CIN] in situ or melanoma in situ) (Stage II portion only)

• Patients with baseline QTcF ≥ 480 msec

• Patients with uncontrolled concurrent illness, active infection requiring i.v. antibiotics, or uncontrolled infections, or a fever > 38.5°C on the day of scheduled dosing

• Patients with serious illnesses, medical conditions, or other medical history, including a prior history of pericarditis/pericardial effusion, or abnormal laboratory results, which, in the investigator's opinion, would be likely to interfere with a patient's participation in the study, or with the interpretation of the results

• Patients who have received any investigational drug within 28 days prior to Day 1 of study entry (an investigational drug is one for which there is no approved indication), or who are receiving concurrent treatment with other experimental drugs or anti-cancer therapy

• Pregnant or lactating women. Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test documented within 72 hours prior to starting study drug or a urine pregnancy test shall be done on Day 1 of Cycle 1

• Women of child bearing potential and their partners must use an acceptable method of contraception while enrolled on this study, and for a period of 3 months following study drug treatment. Patients unwilling or unable to follow this guideline will be excluded. Investigators should follow their Institutional standard regarding acceptable methods of contraception.

• Known hypersensitivity to HDAC inhibitors or to any of the components of mocetinostat

• Known hypersensitivity to gemcitabine

• Any condition that will put the patient at undue risk or discomfort as a result of adherence to study procedures. For example, consider requirement to take mocetinostat with water and recommendation to avoid agents that increase gastric pH

• Any condition (e.g., known or suspected poor compliance, psychological instability, geographical location, etc) that, in the judgment of the investigator, may affect the patient's ability to sign the informed consent and undergo study procedures.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital/Dana Farber Cancer Institute	Boston	Massachusetts	United States	02114
2	University of Michigan	Ann Arbor	Michigan	United States	48109
3	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
4	Ohio State University	Columbus	Ohio	United States	43210
5	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• Sarcoma Alliance for Research through Collaboration

Investigators

• Principal Investigator: Edwin Choy, MD, PhD, MGH, Dana Farber/Harvard Cancer Center
• Principal Investigator: Shreyas Patel, MD, M.D. Anderson Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sarcoma Alliance for Research through Collaboration
• ClinicalTrials.gov Identifier: NCT02303262
• Other Study ID Numbers: SARC018
• First Posted: Nov 27, 2014
• Last Update Posted: Jan 29, 2019
• Last Verified: Nov 1, 2018

• Additional relevant MeSH terms: Leiomyosarcoma; Gemcitabine; Mocetinostat

Study Results

Participant Flow

Arm/Group Title	Mocetinostat and Gemcitabine
Arm/Group Description	For each 21-day cycle, gemcitabine is administered on days 5 and 12 and mocetinostat is administered 3 days a week. Mocetinostat: Mocetinostat is taken orally at 70 mg/dose, 3 days per week, during cycle 1. Dose is increased to 90 mg starting at cycle 2. Gemcitabine: Gemcitabine is administered via intravenous infusion at 1,000 mg/m2 at a rate of approximately 10 mg/m2/minute, on days 5 and 12 of every cycle.
Period Title: Overall Study
STARTED	20
COMPLETED	18
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Mocetinostat and Gemcitabine
Arm/Group Description	For each 21-day cycle, gemcitabine is administered on days 5 and 12 and mocetinostat is administered 3 days a week. Mocetinostat: Mocetinostat is taken orally at 70 mg/dose, 3 days per week, during cycle 1. Dose is increased to 90 mg starting at cycle 2. Gemcitabine: Gemcitabine is administered via intravenous infusion at 1,000 mg/m2 at a rate of approximately 10 mg/m2/minute, on days 5 and 12 of every cycle.
Overall Participants	20
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	17 85%
>=65 years	3 15%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	56.8
Sex: Female, Male (Count of Participants)
Female	14 70%
Male	6 30%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 5%
Not Hispanic or Latino	19 95%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 5%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	3 15%
White	15 75%
More than one race	0 0%
Unknown or Not Reported	1 5%

Outcome Measures

1. Primary Outcome

Title	Response Rate (Per RECIST 1.1)
Description	Response rate (CR or PR) will be calculated by the number of patients achieving a response divided by the number of patients having been evaluated for response. Per Response Evaluation Criteria in Solid Tumors (RECIST): Complete Response (CR) is the disappearance of all target lesions; Partial Response (PR) is at least a 30% decrease in the sum of longest diameters of all target lesions.
Time Frame	27 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mocetinostat and Gemcitabine
Arm/Group Description	For each 21-day cycle, gemcitabine is administered on days 5 and 12 and mocetinostat is administered 3 days a week. Mocetinostat: Mocetinostat is taken orally at 70 mg/dose, 3 days per week, during cycle 1. Dose is increased to 90 mg starting at cycle 2. Gemcitabine: Gemcitabine is administered via intravenous infusion at 1,000 mg/m2 at a rate of approximately 10 mg/m2/minute, on days 5 and 12 of every cycle.
Measure Participants	18
Count of Participants [Participants]	1 5%

2. Secondary Outcome

Title	Duration of Response
Description	The duration of objective response will be measured from the time measurement criteria are first met until disease progression is objectively documented.
Time Frame	27 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mocetinostat and Gemcitabine
Arm/Group Description	For each 21-day cycle, gemcitabine is administered on days 5 and 12 and mocetinostat is administered 3 days a week. Mocetinostat: Mocetinostat is taken orally at 70 mg/dose, 3 days per week, during cycle 1. Dose is increased to 90 mg starting at cycle 2. Gemcitabine: Gemcitabine is administered via intravenous infusion at 1,000 mg/m2 at a rate of approximately 10 mg/m2/minute, on days 5 and 12 of every cycle.
Measure Participants	18
Median (95% Confidence Interval) [months]	2

3. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	Progression free survival is defined as the time from treatment initiation to the earlier date of assessment of objective progression or death by any cause in the absence of progression. Progression Free Survival (PFS) is defined as the time from treatment initiation to the earlier date of assessment of objective progression or death by any cause in the absence of progression. Progression will be assessed by RECIST v. 1.1.
Time Frame	27 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mocetinostat and Gemcitabine
Arm/Group Description	For each 21-day cycle, gemcitabine is administered on days 5 and 12 and mocetinostat is administered 3 days a week. Mocetinostat: Mocetinostat is taken orally at 70 mg/dose, 3 days per week, during cycle 1. Dose is increased to 90 mg starting at cycle 2. Gemcitabine: Gemcitabine is administered via intravenous infusion at 1,000 mg/m2 at a rate of approximately 10 mg/m2/minute, on days 5 and 12 of every cycle.
Measure Participants	18
Median (95% Confidence Interval) [months]	2.0

Adverse Events

Time Frame	through study completion, an average of 3 months
Arm/Group Title	Mocetinostat and Gemcitabine
Arm/Group Description	For each 21-day cycle, gemcitabine is administered on days 5 and 12 and mocetinostat is administered 3 days a week. Mocetinostat: Mocetinostat is taken orally at 70 mg/dose, 3 days per week, during cycle 1. Dose is increased to 90 mg starting at cycle 2. Gemcitabine: Gemcitabine is administered via intravenous infusion at 1,000 mg/m2 at a rate of approximately 10 mg/m2/minute, on days 5 and 12 of every cycle.
All Cause Mortality
	Mocetinostat and Gemcitabine
	Affected / at Risk (%)	# Events
Total	0/20 (0%)
Serious Adverse Events
	Mocetinostat and Gemcitabine
	Affected / at Risk (%)	# Events
Total	12/20 (60%)
Blood and lymphatic system disorders
Anemia	2/20 (10%)	2
Febrile neutropenia	1/20 (5%)	1
Cardiac disorders
Pericardial effusion	1/20 (5%)	1
Gastrointestinal disorders
Constipation	1/20 (5%)	1
Nausea	1/20 (5%)	1
Vomiting	1/20 (5%)	1
General disorders
Failure to thrive	1/20 (5%)	1
Fever	2/20 (10%)	2
Mucositis	1/20 (5%)	1
Non-cardiac chest pain	1/20 (5%)	1
Pain	2/20 (10%)	2
Infections and infestations
Pneumonia	1/20 (5%)	1
Upper respiratory infection	1/20 (5%)	1
Urinary tract infection	1/20 (5%)	1
Investigations
Neutropenia	1/20 (5%)	1
Platelet count decreased	1/20 (5%)	1
Nervous system disorders
Syncope	1/20 (5%)	1
Respiratory, thoracic and mediastinal disorders
Bronchopulmonary hemorrhage	1/20 (5%)	1
Vascular disorders
Hypotension	1/20 (5%)	1
Other (Not Including Serious) Adverse Events
	Mocetinostat and Gemcitabine
	Affected / at Risk (%)	# Events
Total	20/20 (100%)
Blood and lymphatic system disorders
Anemia	8/20 (40%)	28
Pulmonary embolism	1/20 (5%)	1
Cardiac disorders
Palpitations	1/20 (5%)	1
Pericardial tamponade	1/20 (5%)	1
Pericarditis	1/20 (5%)	1
QTCF elevated	1/20 (5%)	1
Ventricular arrhythmia	1/20 (5%)	1
Ear and labyrinth disorders
Vertigo	1/20 (5%)	1
Gastrointestinal disorders
Acid reflux	2/20 (10%)	2
Burping	1/20 (5%)	1
Constipation	3/20 (15%)	3
Diarrhea	4/20 (20%)	8
Dry mouth	2/20 (10%)	2
Flatulence	1/20 (5%)	1
Nausea	8/20 (40%)	12
Stomatitis	1/20 (5%)	1
Vomiting	5/20 (25%)	8
General disorders
Achy	1/20 (5%)	1
Chills	2/20 (10%)	2
Cord compression	1/20 (5%)	1
Fatigue	12/20 (60%)	22
Fever	1/20 (5%)	1
Malaise	1/20 (5%)	1
Night sweats	1/20 (5%)	1
Pain	2/20 (10%)	3
Infections and infestations
Pharyngitis	1/20 (5%)	1
Fungal infection	1/20 (5%)	1
Thrush	1/20 (5%)	1
Injury, poisoning and procedural complications
Bruising	1/20 (5%)	1
Fracture	1/20 (5%)	1
Powerport soreness	1/20 (5%)	1
Investigations
Absolute neutrophil count decreased	1/20 (5%)	3
Alanine Aminotransferase increased	1/20 (5%)	2
Alkaline phosphatase increased	2/20 (10%)	3
Creatinine increased	1/20 (5%)	2
Ejection fraction decreased	1/20 (5%)	1
Elevated LFTs	1/20 (5%)	1
GGT increased	1/20 (5%)	1
Lymphocyte count decreased	2/20 (10%)	5
Neutrophil count decreased	8/20 (40%)	18
Platelet count decreased	6/20 (30%)	16
Weight loss	1/20 (5%)	1
White blood cell decreased	4/20 (20%)	10
Metabolism and nutrition disorders
Anorexia	6/20 (30%)	6
Decreased appetite	2/20 (10%)	2
Dehydration	2/20 (10%)	2
Hypoalbuminemia	2/20 (10%)	2
Hypocalcemia	1/20 (5%)	1
Hypokalemia	2/20 (10%)	2
Hyponatremia	1/20 (5%)	1
Hypophosphatemia	1/20 (5%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	1/20 (5%)	3
Back pain	2/20 (10%)	2
Calf tenderness/burning	1/20 (5%)	1
Generalized muscle weakness	1/20 (5%)	1
Sciatic pain	1/20 (5%)	1
Muscle cramps	1/20 (5%)	1
Myalgia	1/20 (5%)	1
Neck pain	1/20 (5%)	1
Neck stiffness	1/20 (5%)	1
Thigh pain	1/20 (5%)	1
Right sided chest pain	1/20 (5%)	1
Sharp left sided pain	1/20 (5%)	1
Shoulder pain	1/20 (5%)	1
Nervous system disorders
Dizziness	2/20 (10%)	3
Dysgeusia	4/20 (20%)	4
Headache	2/20 (10%)	2
Memory impairment	1/20 (5%)	1
Paresthesia	1/20 (5%)	1
Peripheral sensory neuropathy	1/20 (5%)	3
Psychiatric disorders
Insomnia	4/20 (20%)	4
Renal and urinary disorders
Hydronephrosis	1/20 (5%)	1
Respiratory, thoracic and mediastinal disorders
Cough	1/20 (5%)	1
Dyspnea	6/20 (30%)	6
Laryngeal inflammation	1/20 (5%)	1
Nasal irritation	1/20 (5%)	1
Sore throat	1/20 (5%)	1
Throat irritation	1/20 (5%)	1
Voice alteration	1/20 (5%)	1
Skin and subcutaneous tissue disorders
Dry skin	1/20 (5%)	1
Erythematous neck rash	1/20 (5%)	1
Facial acne	1/20 (5%)	1
Sore nostril	1/20 (5%)	1
Pruritic rash	1/20 (5%)	1
Vascular disorders
Hypertension	2/20 (10%)	2
Hypotension	1/20 (5%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.