Trabectedin in Treating Patients With Advanced, Persistent, or Recurrent Leiomyosarcoma of the Uterus

• Sponsor: Gynecologic Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00379145
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 20
• Locations: 32
• Arm: 1
• Patients Per Site: 0.6

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as trabectedin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This phase II trial is studying how well trabectedin works in treating patients with advanced, persistent, or recurrent leiomyosarcoma of the uterus.

Condition or Disease	Intervention/Treatment	Phase
Sarcoma	Drug: trabectedin	Phase 2

Detailed Description

OBJECTIVES:

• Determine the antitumor activity of trabectedin, as measured by frequency and duration of objective response, in patients with advanced, persistent, or recurrent uterine leiomyosarcoma.

• Determine the nature and degree of toxicity of this drug in these patients.

OUTLINE: This is a nonrandomized, multicenter study.

Patients receive trabectedin IV continuously over 24 hours on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients who achieve a confirmed complete response may receive at least 2 additional courses.

After completion of study treatment, patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 43 patients will be accrued for this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Evaluation of Trabectedin (Yondelis, R279741) in the Treatment of Advanced, Persistent, or Recurrent Uterine Leiomyosarcomas
• Study Start Date: Jun 1, 2007
• Actual Primary Completion Date: Jan 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Trabectedin Trabectedin IV over 24 hours every 3 weeks	Drug: trabectedin

Outcome Measures

Primary Outcome Measures

1. Number of Patients With Objective Tumor Response Rate (Complete Response [CR] or Partial Response [PR]) Using RECIST Version 1.0 [CT scan or MRI if used to follow lesion for measurable disease every other cycle until disease progression for up to 5 years.]

   RECIST 1.0 defines complete response as the disappearance of all target lesions and non-target lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart. Partial response is defined as at least a 30% decrease in the sum of longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD. There can be no unequivocal progression of non-target lesions and no new lesions. Documentation by two disease assessments at least 4 weeks apart is required. In the case where the ONLY target lesion is a solitary pelvic mass measured by physical exam, which is not radiographically measurable, a 50% decrease in the LD is required. These patients will have their response classified according to the definitions stated above. Complete and partial responses are included in the objective tumor response rate.

2. Incidence of Adverse Effects as Assessed by Common Terminology Criteria for Adverse Events Version 3.0 [Assessed every cycle while on treatment, 30 days after the last cycle of treatment, and up to 5 years in follow-up]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Histologically confirmed uterine leiomyosarcoma

• Histological confirmation of original primary tumor required

• Advanced, persistent, or recurrent disease

• Documented disease progression

• Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques, including palpation, plain x-ray, CT scan, and MRI OR ≥ 10 mm by spiral CT scan

• At least 1 target lesion

• Tumors within a previously irradiated field are considered nontarget lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiotherapy

• Ineligible for a higher priority GOG protocol (i.e., any active phase III GOG protocol for the same patient population)

PATIENT CHARACTERISTICS:

• GOG performance status 0-2

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• Platelet count ≥ 100,000/mm³

• Absolute neutrophil count ≥ 1,500/mm³

• Hemoglobin > 9.0 g/dL

• Creatinine ≤ 1.5 times upper limit of normal (ULN)

• Bilirubin normal

• AST ≤ 2.5 times ULN

• Alkaline phosphatase ≤ 1.5 times ULN

• CPK ≤ ULN

• No active infection requiring antibiotics (except for patients with uncomplicated UTI)

• No neuropathy (sensory or motor) > grade 1

• No other invasive malignancy within the past 5 years except for nonmelanoma skin cancer

• No known active liver disease or hepatitis

• Must be willing/able to have a central venous catheter

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• Recovered from prior surgery, radiotherapy, or other therapy

• No prior cancer treatment that would preclude study therapy

• No prior cytotoxic chemotherapy or biologic therapy for uterine sarcoma

• No prior chemotherapy for any abdominal or pelvic tumor within the past 5 years

• Prior adjuvant chemotherapy for localized breast cancer is allowed provided it was completed more than 3 years ago and there is no evidence of recurrent or metastatic disease

• No prior trabectedin

• No prior radiotherapy within the past 5 years to any portion of the abdominal cavity or pelvis other than for treatment of uterine sarcoma

• Prior radiotherapy for localized cancer of the breast, head and neck or skin is allowed, provided that it was completed more than 3 years ago and there is no evidence of recurrent or metastatic disease

• At least 1 week since prior hormonal therapy for the malignancy (continuation of hormone replacement therapy is permitted)

• No concurrent amifostine or other protective agents

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	USC/Norris Comprehensive Cancer Center and Hospital	El Pueblo De Nuestra Señora De Los Ángeles De Porciúncula	California	United States	90089-9181
2	Helen and Harry Gray Cancer Center at Hartford Hospital	Hartford	Connecticut	United States	06102-5037
3	George Bray Cancer Center at the Hospital of Central Connecticut - New Britain Campus	New Britain	Connecticut	United States	06050
4	Washington Cancer Institute at Washington Hospital Center	Washington	District of Columbia	United States	20010
5	MBCCOP - Medical College of Georgia Cancer Center	Augusta	Georgia	United States	30912
6	Central Georgia Gynecologic Oncology	Macon	Georgia	United States	31201
7	Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center	Savannah	Georgia	United States	31403-3089
8	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois	United States	60611-3013
9	Hinsdale Hematology Oncology Associates	Hinsdale	Illinois	United States	60521
10	St. Vincent Indianapolis Hospital	Indianapolis	Indiana	United States	46260
11	Holden Comprehensive Cancer Center at University of Iowa	Iowa City	Iowa	United States	52242-1002
12	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21231-2410
13	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007-3731
14	St. John's Regional Health Center	Springfield	Missouri	United States	65804
15	Women's Cancer Center - Lake Mead	Las Vegas	Nevada	United States	89102
16	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87131-5636
17	SUNY Downstate Medical Center	Brooklyn	New York	United States	11203
18	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021
19	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina	United States	27599-7295
20	Blumenthal Cancer Center at Carolinas Medical Center	Charlotte	North Carolina	United States	28232-2861
21	Presbyterian Cancer Center at Presbyterian Hospital	Charlotte	North Carolina	United States	28233-3549
22	Duke Comprehensive Cancer Center	Durham	North Carolina	United States	27710
23	Case Comprehensive Cancer Center	Cleveland	Ohio	United States	44106-5065
24	MetroHealth Cancer Care Center at MetroHealth Medical Center	Cleveland	Ohio	United States	44109
25	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio	United States	44195
26	Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center	Columbus	Ohio	United States	43210-1240
27	Riverside Methodist Hospital Cancer Care	Columbus	Ohio	United States	43214-3998
28	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio	United States	45409
29	Lake/University Ireland Cancer Center	Mentor	Ohio	United States	44060
30	Oklahoma University Cancer Institute	Oklahoma City	Oklahoma	United States	73104
31	Rosenfeld Cancer Center at Abington Memorial Hospital	Abington	Pennsylvania	United States	19001
32	University of Wisconsin Paul P. Carbone Comprehensive Cancer Center	Madison	Wisconsin	United States	53792-6164

Sponsors and Collaborators

• Gynecologic Oncology Group
• National Cancer Institute (NCI)

Investigators

• Study Chair: Bradley J. Monk, MD, Chao Family Comprehensive Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

• Tewari D, Saffari B, Cowan C, Wallick AC, Koontz MZ, Monk BJ. Activity of trabectedin (ET-743, Yondelis) in metastatic uterine leiomyosarcoma. Gynecol Oncol. 2006 Sep;102(3):421-4. Epub 2006 Jun 23.

• Responsible Party: Gynecologic Oncology Group
• ClinicalTrials.gov Identifier: NCT00379145
• Other Study ID Numbers: GOG-0087M; CDR0000502192; NCI-2009-00573
• First Posted: Sep 21, 2006
• Last Update Posted: Dec 12, 2017
• Last Verified: May 1, 2015

• Keywords provided by Gynecologic Oncology Group: uterine leiomyosarcoma; recurrent uterine sarcoma; stage III uterine sarcoma; stage IV uterine sarcoma
• Additional relevant MeSH terms: Sarcoma; Leiomyosarcoma; Trabectedin

Study Results

Participant Flow

Recruitment Details	This trial was opened to patient entry on June 4, 2007 and was closed to accrual on November 3, 2008.

Arm/Group Title	Trabectidin
Arm/Group Description	Trabectedin 1.5 mg/m2 IV over 24 hours every 3 weeks (one cycle) until disease progression or adverse effects prohibit further therapy
Period Title: Overall Study
STARTED	20
COMPLETED	20
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Trabectidin
Arm/Group Description	Trabectedin 1.5 mg/m2 IV over 24 hours every 3 weeks (one cycle) until disease progression or adverse effects prohibit further therapy
Overall Participants	20
Age, Customized (Count of Participants)
<40 years	1 5%
40-49 years	3 15%
50-59 years	5 25%
60-69 years	7 35%
70-79 years	3 15%
>79 years	1 5%
Sex: Female, Male (Count of Participants)
Female	20 100%
Male	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 5%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	4 20%
White	15 75%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Patients With Objective Tumor Response Rate (Complete Response [CR] or Partial Response [PR]) Using RECIST Version 1.0
Description	RECIST 1.0 defines complete response as the disappearance of all target lesions and non-target lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart. Partial response is defined as at least a 30% decrease in the sum of longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD. There can be no unequivocal progression of non-target lesions and no new lesions. Documentation by two disease assessments at least 4 weeks apart is required. In the case where the ONLY target lesion is a solitary pelvic mass measured by physical exam, which is not radiographically measurable, a 50% decrease in the LD is required. These patients will have their response classified according to the definitions stated above. Complete and partial responses are included in the objective tumor response rate.
Time Frame	CT scan or MRI if used to follow lesion for measurable disease every other cycle until disease progression for up to 5 years.

Outcome Measure Data

Analysis Population Description

Eligible and treated patients

Arm/Group Title	Trabectidin
Arm/Group Description	Trabectedin 1.5 mg/m2 IV over 24 hours every 3 weeks (one cycle) until disease progression or adverse effects prohibit further therapy
Measure Participants	20
Partial response	2 10%
Complete response	0 0%

2. Primary Outcome

Title	Incidence of Adverse Effects as Assessed by Common Terminology Criteria for Adverse Events Version 3.0
Time Frame	Assessed every cycle while on treatment, 30 days after the last cycle of treatment, and up to 5 years in follow-up

Outcome Measure Data

Analysis Population Description

Eligible and treated patients

Arm/Group Title	Grade 0	Grade 1 (CTCAE v 3.0)	Grade 2 (CTCAE v 3.0)	Grade 3 (CTCAE v 3.0)	Grade 4 (CTCAE v 3.0)
Arm/Group Description	Number of patients who did not experience the specified AE.	Number of patients who experienced a grade 1 event using Common Terminology Criteria for Adverse Events v3.0 (CTCAE).	Number of patients who experienced a grade 2 event using Common Terminology Criteria for Adverse Events v3.0 (CTCAE).	Number of patients who experienced a grade 3 event using Common Terminology Criteria for Adverse Events v3.0 (CTCAE).	Number of patients who experienced a grade 4 event using Common Terminology Criteria for Adverse Events v3.0 (CTCAE).
Measure Participants	20	20	20	20	20
Leukopenia	2 10%	0 NaN	7 NaN	10 NaN	1 NaN
Thrombocytopenia	13 65%	4 NaN	0 NaN	3 NaN	0 NaN
Neutropenia	2 10%	0 NaN	2 NaN	11 NaN	5 NaN
Anemia	3 15%	10 NaN	6 NaN	1 NaN	0 NaN
Other hematologic	18 90%	0 NaN	2 NaN	0 NaN	0 NaN
Coagulation	19 95%	1 NaN	0 NaN	0 NaN	0 NaN
Hemorrhage	18 90%	2 NaN	0 NaN	0 NaN	0 NaN
Nausea	3 15%	11 NaN	6 NaN	0 NaN	0 NaN
Vomiting	7 35%	10 NaN	3 NaN	0 NaN	0 NaN
Bilirubin	19 95%	1 NaN	0 NaN	0 NaN	0 NaN
ALT	9 45%	4 NaN	5 NaN	2 NaN	0 NaN
Alkaline Phosphatase	19 95%	1 NaN	0 NaN	0 NaN	0 NaN
Dermatologic	14 70%	4 NaN	2 NaN	0 NaN	0 NaN
Infection	17 85%	0 NaN	2 NaN	1 NaN	0 NaN
Pulmonary	15 75%	4 NaN	1 NaN	0 NaN	0 NaN
Metabolic	8 40%	5 NaN	4 NaN	3 NaN	0 NaN
Lymphatics	16 80%	4 NaN	0 NaN	0 NaN	0 NaN
Pain	8 40%	10 NaN	2 NaN	0 NaN	0 NaN
Constitutional	17 85%	3 NaN	0 NaN	0 NaN	0 NaN
Fatigue	5 25%	8 NaN	7 NaN	0 NaN	0 NaN
Musculoskeletal	15 75%	4 NaN	1 NaN	0 NaN	0 NaN
Neurotoxicity	16 80%	4 NaN	0 NaN	0 NaN	0 NaN
Peripheral neuropathy	18 90%	2 NaN	0 NaN	0 NaN	0 NaN
Renal	19 95%	1 NaN	0 NaN	0 NaN	0 NaN
Ocular	16 80%	3 NaN	1 NaN	0 NaN	0 NaN
Vascular	19 95%	0 NaN	0 NaN	1 NaN	0 NaN
Flu-like syndrome	19 95%	0 NaN	1 NaN	0 NaN	0 NaN

Adverse Events

Time Frame	Assessed every cycle while on treatment, 30 days after the last cycle of treatment, and up to 5 years in follow-up
Arm/Group Title	Trabectidin
Arm/Group Description	Trabectedin 1.5 mg/m2 IV over 24 hours every 3 weeks (one cycle) until disease progression or adverse effects prohibit further therapy
All Cause Mortality
	Trabectidin
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Trabectidin
	Affected / at Risk (%)	# Events
Total	4/20 (20%)
Blood and lymphatic system disorders
Neutrophils	2/20 (10%)
Gastrointestinal disorders
Diarrhea	1/20 (5%)
Infections and infestations
Inf W/Nml Or Gr 1 Or 2 Anc: Neck Nos	1/20 (5%)
Metabolism and nutrition disorders
Hypokalemia	1/20 (5%)
Vascular disorders
Thrombosis/Thrombus/Embolism	1/20 (5%)
Other (Not Including Serious) Adverse Events
	Trabectidin
	Affected / at Risk (%)	# Events
Total	20/20 (100%)
Blood and lymphatic system disorders
Neutrophils	18/20 (90%)
Platelets	8/20 (40%)
Leukocytes	18/20 (90%)
Lymphopenia	2/20 (10%)
Hemoglobin	17/20 (85%)
Edema: Limb	5/20 (25%)
Edema: Head And Neck	1/20 (5%)
Cardiac disorders
Palpitations	1/20 (5%)
Cardiac Arrhythmia - Other	1/20 (5%)
Ventricular Arrhythmia - Tachycardia	1/20 (5%)
Hypertension	1/20 (5%)
Cardiac General - Other	1/20 (5%)
Hypotension	1/20 (5%)
Ear and labyrinth disorders
Tinnitus	1/20 (5%)
Endocrine disorders
Hot Flashes	3/20 (15%)
Eye disorders
Ocular/Visual - Other	1/20 (5%)
Flashing Lights/Floaters	1/20 (5%)
Blurred Vision	3/20 (15%)
Gastrointestinal disorders
Flatulence	2/20 (10%)
Gastritis	1/20 (5%)
Hemorrhoids	1/20 (5%)
Heartburn	2/20 (10%)
Dysphagia	1/20 (5%)
Distention	1/20 (5%)
Taste Alteration	2/20 (10%)
Mucositis (Functional/Sympt) - Oral Cavity	1/20 (5%)
Obstruction, Gi - Small Bowel Nos	1/20 (5%)
Mucositis (Clinical Exam) - Oral Cavity	1/20 (5%)
Vomiting	13/20 (65%)
Anorexia	6/20 (30%)
Dehydration	1/20 (5%)
Constipation	14/20 (70%)
Nausea	17/20 (85%)
Gastrointestinal - Other	2/20 (10%)
Diarrhea	8/20 (40%)
General disorders
Weight Gain	4/20 (20%)
Fever	2/20 (10%)
Weight Loss	2/20 (10%)
Rigors/Chills	1/20 (5%)
Fatigue	16/20 (80%)
Pain - Other	1/20 (5%)
Pain: Pelvis	2/20 (10%)
Pain: Chest /Thorax Nos	1/20 (5%)
Pain: Chest Wall	2/20 (10%)
Pain: Throat/Pharynx/Larynx	2/20 (10%)
Pain: Head/Headache	9/20 (45%)
Pain: Neck	2/20 (10%)
Pain: Extremity-Limb	6/20 (30%)
Pain: Back	3/20 (15%)
Pain: Joint	5/20 (25%)
Pain: Stomach	1/20 (5%)
Pain: Oral Cavity	3/20 (15%)
Pain: Abdominal Pain Nos	3/20 (15%)
Pain: Liver	1/20 (5%)
Pain: Muscle	3/20 (15%)
Flu-Like Syndrome	1/20 (5%)
Immune system disorders
Rhinitis	1/20 (5%)
Infections and infestations
Febrile Neutropenia	1/20 (5%)
Inf W/Nml Or Gr 1 Or 2 Anc: Urinary Tract Nos	1/20 (5%)
Inf W/Nml Or Gr 1 Or 2 Anc: Pharynx	1/20 (5%)
Metabolism and nutrition disorders
Ast	10/20 (50%)
Metabolic/Laboratory - Other	3/20 (15%)
Cholesterol,serum High	1/20 (5%)
Proteinuria	2/20 (10%)
Creatinine	1/20 (5%)
Hypoalbuminemia	3/20 (15%)
Alt	12/20 (60%)
Alkaline Phosphatase	1/20 (5%)
Bilirubin	1/20 (5%)
Hypophosphatemia	1/20 (5%)
Hyponatremia	3/20 (15%)
Cpk	1/20 (5%)
Hypocalcemia	2/20 (10%)
Hyperglycemia	6/20 (30%)
Hypokalemia	3/20 (15%)
Hypomagnesemia	3/20 (15%)
Musculoskeletal and connective tissue disorders
Musculoskeletal/St: Other	1/20 (5%)
Muscle Weakness - Whole Body/Generalized	2/20 (10%)
Muscle Weakness - Extremity-Upper	1/20 (5%)
Muscle Weakness - Extremity-Lower	3/20 (15%)
Nervous system disorders
Neurology - Other	2/20 (10%)
Mood Alteration - Depression	4/20 (20%)
Mood Alteration - Anxiety	2/20 (10%)
Mood Alteration - Agitation	1/20 (5%)
Dizziness	1/20 (5%)
Neuropathy-Sensory	5/20 (25%)
Neuropathy-Motor	2/20 (10%)
Renal and urinary disorders
Renal/Genitourinary - Other	1/20 (5%)
Urinary Frequency	1/20 (5%)
Reproductive system and breast disorders
Vaginal Discharge	1/20 (5%)
Respiratory, thoracic and mediastinal disorders
Pulmonary: Other	1/20 (5%)
Pneumothorax	1/20 (5%)
Cough	4/20 (20%)
Dyspnea	7/20 (35%)
Skin and subcutaneous tissue disorders
Hair Loss/Alopecia (Scalp Or Body)	1/20 (5%)
Erythema Multiforme	1/20 (5%)
Bruising	2/20 (10%)
Rash	3/20 (15%)
Dry Skin	1/20 (5%)
Flushing	2/20 (10%)
Dermatology/Skin - Other	1/20 (5%)
Hyperpigmentation	2/20 (10%)
Vascular disorders
Inr	2/20 (10%)
Ptt	1/20 (5%)
Hemorrhage, Gi - Rectum	1/20 (5%)
Hemorrhage/Pulmonary - Nose	2/20 (10%)
Vascular - Other	1/20 (5%)
Thrombosis/Embolism (Vascular Access-Related)	2/20 (10%)
Thrombosis/Thrombus/Embolism	1/20 (5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.