Safety and Efficacy Study of Glufosfamide in Ovarian Cancer

• Sponsor: Eleison Pharmaceuticals LLC. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00442598
• Collaborator: (none)
• Enrollment: 17
• Locations: 10
• Arms: 3
• Duration (Months): 15
• Patients Per Site: 1.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Primary Objectives:

• To evaluate the effect of glufosfamide on the serum concentrations of CA125 in subjects with ovarian cancer

• To evaluate the safety of weekly glufosfamide dosing in subjects with ovarian cancer as compared with every 21-day dosing

Secondary objectives:

• To evaluate the efficacy of glufosfamide in subjects with ovarian cancer as measured by objective response rate, duration of response, progression-free survival, and overall survival

• To evaluate the pharmacokinetics of glufosfamide and isophosphoramide mustard during and after treatment

Exploratory objective:

• To correlate efficacy endpoints with expression of tumor-associated glucose transporter proteins

Condition or Disease	Intervention/Treatment	Phase
Ovarian Cancer	Drug: Glufosfamide	Phase 2

Detailed Description

Open-label, multicenter, Phase 2 dose escalation study. Subjects will be randomized to receive either once every three weeks dosing regimen or the weekly dosing regimen. Randomization will utilize a 2:1 ratio with two-thirds of the subjects randomized to the weekly dosing regimen.

In the weekly dosing schedule, treatment with glufosfamide 2,500 mg/m2 will be initiated only after the 1,660 mg/m2 treatment cohort has been enrolled and there is evidence that the dose of 1,660 mg/m2 has been well tolerated (See below Section on Pharmacokinetic/Statistical Analyses).

Study Design

• Study Type: Interventional
• Actual Enrollment: 17 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label Phase 2 Study of the Safety and Efficacy of Glufosfamide in Ovarian Cancer
• Study Start Date: Jan 1, 2007
• Actual Primary Completion Date: Apr 1, 2008
• Actual Study Completion Date: Apr 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Glufosfamide q21 days 1-hour infusion of glufosfamide at a dose of 5,000 mg/m2 on Day 1 of a 21-day cycle	Drug: Glufosfamide
Experimental: Glufosfamide q7 days low 1-hour infusion of glufosfamide at a dose of 1,660 mg/m2 on Days 1, 8 and 15 of a 21-day cycle	Drug: Glufosfamide
Experimental: Glufosfamide q7 days high 1-hour infusion of glufosfamide at a dose of 2,500 mg/m2 on Days 1, 8 and 15 of a 21-day cycle	Drug: Glufosfamide

Outcome Measures

Primary Outcome Measures

1. CA 125 Response Rate [Duration of study, up to 18 weeks.]

   Reduction in blood levels of CA 125 of >50% from baseline, confirmed at the next study cycle.

Secondary Outcome Measures

1. Objective Response Rate [Duration of study, up to 18 weeks.]

   Objective response rate measured by RECIST v1.0

2. Progression-free Survival [Median measured in months]

   Time from initiation of study drug to disease progression or death on study

3. Overall Survival [Median measured in months, until death or censorship at analysis.]

   Time from initiation of study drug to death.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• At least 18 years of age

• Ability to understand the purposes and risks of the study and has signed a written informed consent form approved by the investigator's IRB/Ethics Committee

• Pathologically confirmed epithelial ovarian cancer, peritoneal serous cancer, or carcinoma of the fallopian tube

• Prior treatment with at least one platinum-based chemotherapy

• Evidence of resistance to most recent platinum-containing regimen (relapsed during or within 6 months after completing chemotherapy)

• Evidence of CA 125 progression after most recent chemotherapy defined as either:

• CA 125 at least 40 U/mL for patients with elevated CA 125 that decreased to <20 U/mL on therapy; or

• CA 125 at least 40 U/mL and at least a 50% increase over the nadir value for patients with elevated CA 125 that did not decrease to <20 U/mL on therapy.

CA 125 must meet criteria on two occasions not less than one week apart if the CA 125 has increased by at least 100% (i.e., doubled). There must be 3 consecutive increasing measurements over a period of at least two weeks if the CA 125 has increased by at least 50% but less than 100%.

• Elevated serum CA125 (≥40 U/mL) within 2 weeks prior to starting treatment

• At least one target or nontarget lesion by RECIST

• A minimum of 21 days between prior chemotherapy, radiation therapy, immunotherapy, or other anti-tumor therapy and study entry

• Recovered from reversible toxicities of prior therapy

• ECOG score of 0 or 1

• ANC ≥ 1,500/µL, platelets ≥ 100,000/µL, hemoglobin ≥9 g/dL

• Total bilirubin ≤ 1.5-fold ULN, AST/ALT ≤ 2.5-fold ULN (≤ 5-fold ULN if liver metastases)

• Creatinine clearance ≥ 60 mL/min (calculated by Cockcroft-Gault formula)

• All women of childbearing potential must have a negative serum pregnancy test and must agree to use effective means of contraception (surgical sterilization or the use of barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel or an IUD) from entry into the study through 6 months after the last dose

Exclusion Criteria:

• Concomitant or planned hormonal therapy, radiation therapy, biologic therapy, chemotherapy or other systemic antitumor therapy for ovarian cancer other than protocol therapy

• Symptomatic brain metastases

• Active clinically significant infection requiring antibiotics

• Known HIV positive or active hepatitis B or C

• Recent (one year) history or symptoms of cardiovascular disease (NYHA Class 2, 3, or 4), particularly coronary artery disease, arrhythmias or conduction defects with risk of cardiovascular instability, uncontrolled hypertension, clinically significant pericardial effusion, congestive heart failure or stroke

• Other active malignancies (other than treated non-melanoma skin cancer or treated in situ cancer) within the past 5 years

• Major surgery within 3 weeks of the start of study treatment, without complete recovery

• Females who are pregnant or breast-feeding

• Participation in an investigational drug or device study within 28 days of the first day of dosing on this study

• Concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study

• Unwillingness or inability to comply with the study protocol for any other reason

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Premiere Oncology of Arizona	Scottsdale	Arizona	United States	85260
2	Arizona Cancer Center	Tucson	Arizona	United States	85724
3	California Cancer Center	Greenbrae	California	United States	94904
4	UCI Chao Family Comprehensive Cancer Center	Orange	California	United States	92868
5	Indiana University Cancer Center	Indianapolis	Indiana	United States	46202
6	Louisville Oncology Clinical Research Program	Louisville	Kentucky	United States	40202
7	New Mexico Cancer Care Alliance	Albuquerque	New Mexico	United States	87106
8	Gabrail Cancer Center	Canton	Ohio	United States	44718
9	Gynecologic Oncology Research & Development, LLC	Greenville	South Carolina	United States	29601
10	Harrington Cancer Center	Amarillo	Texas	United States	79106

Sponsors and Collaborators

• Eleison Pharmaceuticals LLC.

Investigators

• Principal Investigator: David Alberts, MD, University of Arizona
• Principal Investigator: Michael Gordon, MD, Premiere Oncology of Arizona
• Principal Investigator: Daniela Matei, MD, Indiana University School of Medicine
• Principal Investigator: Peter D Eisenberg, MD, California Cancer Center
• Principal Investigator: Larry Puls, MD, Gynecologic Oncology Research & Development, LLC
• Principal Investigator: Krishnansu Tewari, MD, UCI Chao Family Comprehensive Cancer Center
• Principal Investigator: Nashat Gabrail, MD, Gabrail Cancer Center
• Principal Investigator: Jeffrey Goldberg, MD, Louisville Oncology Clinical Research Program
• Principal Investigator: Claire Verschraegen, M.D., New Mexico Cancer Care Alliance
• Principal Investigator: William Robinson, MD, Harrington Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eleison Pharmaceuticals LLC.
• ClinicalTrials.gov Identifier: NCT00442598
• Other Study ID Numbers: TH-CR-303
• First Posted: Mar 2, 2007
• Last Update Posted: Mar 10, 2015
• Last Verified: Mar 1, 2015

• Keywords provided by Eleison Pharmaceuticals LLC.: Ovarian; Cancer; CA-125; Third-line; Glufosfamide
• Additional relevant MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial

Study Results

Participant Flow

Arm/Group Title	Glufosfamide q21 Days	Glufosfamide q7 Days Low	Glufosfamide q7 Days High
Arm/Group Description	1-hour infusion of glufosfamide at a dose of 5,000 mg/m2 on Day 1 of a 21-day cycle Glufosfamide	1-hour infusion of glufosfamide at a dose of 1,660 mg/m2 on Days 1, 8 and 15 of a 21-day cycle Glufosfamide	1-hour infusion of glufosfamide at a dose of 2,500 mg/m2 on Days 1, 8 and 15 of a 21-day cycle Glufosfamide
Period Title: Overall Study
STARTED	7	10	0
Two Cycles	5	6	0
COMPLETED	1	2	0
NOT COMPLETED	6	8	0

Baseline Characteristics

Arm/Group Title	Glufosfamide q21 Days	Glufosfamide q7 Days Low	Glufosfamide q7 Days High	Total
Arm/Group Description	1-hour infusion of glufosfamide at a dose of 5,000 mg/m2 on Day 1 of a 21-day cycle Glufosfamide	1-hour infusion of glufosfamide at a dose of 1,660 mg/m2 on Days 1, 8 and 15 of a 21-day cycle Glufosfamide	1-hour infusion of glufosfamide at a dose of 2,500 mg/m2 on Days 1, 8 and 15 of a 21-day cycle Glufosfamide	Total of all reporting groups
Overall Participants	7	10	0	17
Age (participants) [Number]
<=18 years	0 0%	0 0%	0 NaN
Between 18 and 65 years	6 85.7%	6 60%	12 Infinity
>=65 years	1 14.3%	4 40%	5 Infinity
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	60	52	58
Gender (participants) [Number]
Female	7 100%	10 100%	17 Infinity
Male	0 0%	0 0%	0 NaN
Race (NIH/OMB) (participants) [Number]
American Indian or Alaska Native	0 0%	0 0%	0 NaN
Asian	0 0%	0 0%	0 NaN
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 NaN
Black or African American	0 0%	0 0%	0 NaN
White	7 100%	10 100%	17 Infinity
More than one race	0 0%	0 0%	0 NaN
Unknown or Not Reported	0 0%	0 0%	0 NaN

Outcome Measures

1. Primary Outcome

Title	CA 125 Response Rate
Description	Reduction in blood levels of CA 125 of >50% from baseline, confirmed at the next study cycle.
Time Frame	Duration of study, up to 18 weeks.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Glufosfamide q21 Days	Glufosfamide q7 Days Low	Glufosfamide q7 Days High
Arm/Group Description	1-hour infusion of glufosfamide at a dose of 5,000 mg/m2 on Day 1 of a 21-day cycle Glufosfamide	1-hour infusion of glufosfamide at a dose of 1,660 mg/m2 on Days 1, 8 and 15 of a 21-day cycle Glufosfamide	1-hour infusion of glufosfamide at a dose of 2,500 mg/m2 on Days 1, 8 and 15 of a 21-day cycle Glufosfamide
Measure Participants	7	10	0
Partial response	1 14.3%	0 0%
Stable disease	6 85.7%	10 100%

2. Secondary Outcome

Title	Objective Response Rate
Description	Objective response rate measured by RECIST v1.0
Time Frame	Duration of study, up to 18 weeks.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Glufosfamide q21 Days	Glufosfamide q7 Days Low	Glufosfamide q7 Days High
Arm/Group Description	1-hour infusion of glufosfamide at a dose of 5,000 mg/m2 on Day 1 of a 21-day cycle Glufosfamide	1-hour infusion of glufosfamide at a dose of 1,660 mg/m2 on Days 1, 8 and 15 of a 21-day cycle Glufosfamide	1-hour infusion of glufosfamide at a dose of 2,500 mg/m2 on Days 1, 8 and 15 of a 21-day cycle Glufosfamide
Measure Participants	7	10	0
Stable disease	3 42.9%	3 30%
Progressive disease	4 57.1%	7 70%

3. Secondary Outcome

Title	Progression-free Survival
Description	Time from initiation of study drug to disease progression or death on study
Time Frame	Median measured in months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Glufosfamide q21 Days	Glufosfamide q7 Days Low	Glufosfamide q7 Days High
Arm/Group Description	1-hour infusion of glufosfamide at a dose of 5,000 mg/m2 on Day 1 of a 21-day cycle Glufosfamide	1-hour infusion of glufosfamide at a dose of 1,660 mg/m2 on Days 1, 8 and 15 of a 21-day cycle Glufosfamide	1-hour infusion of glufosfamide at a dose of 2,500 mg/m2 on Days 1, 8 and 15 of a 21-day cycle Glufosfamide
Measure Participants	7	10	0
Median (Full Range) [months]	1.2	1.9

4. Secondary Outcome

Title	Overall Survival
Description	Time from initiation of study drug to death.
Time Frame	Median measured in months, until death or censorship at analysis.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Glufosfamide q21 Days	Glufosfamide q7 Days Low	Glufosfamide q7 Days High
Arm/Group Description	1-hour infusion of glufosfamide at a dose of 5,000 mg/m2 on Day 1 of a 21-day cycle Glufosfamide	1-hour infusion of glufosfamide at a dose of 1,660 mg/m2 on Days 1, 8 and 15 of a 21-day cycle Glufosfamide	1-hour infusion of glufosfamide at a dose of 2,500 mg/m2 on Days 1, 8 and 15 of a 21-day cycle Glufosfamide
Measure Participants	7	10	0
Median (Full Range) [months]	5.6	6.8

Adverse Events

Arm/Group Title	Glufosfamide q21 Days		Glufosfamide q7 Days Low
Arm/Group Description	1-hour infusion of glufosfamide at a dose of 5,000 mg/m2 on Day 1 of a 21-day cycle Glufosfamide		1-hour infusion of glufosfamide at a dose of 1,660 mg/m2 on Days 1, 8 and 15 of a 21-day cycle Glufosfamide
All Cause Mortality
	Glufosfamide q21 Days		Glufosfamide q7 Days Low
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Glufosfamide q21 Days		Glufosfamide q7 Days Low
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/7 (28.6%)		3/10 (30%)
Gastrointestinal disorders
Small intestinal obstruction	1/7 (14.3%)	1	0/10 (0%)	0
Renal and urinary disorders
Renal failure	1/7 (14.3%)	1	0/10 (0%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnea	0/7 (0%)	0	2/10 (20%)	2
Pulmonary embolism	0/7 (0%)	0	1/10 (10%)	1
Vascular disorders
Deep vein thrombosis	0/7 (0%)	0	1/10 (10%)	1
Other (Not Including Serious) Adverse Events
	Glufosfamide q21 Days		Glufosfamide q7 Days Low
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/7 (100%)		9/10 (90%)
Blood and lymphatic system disorders
Anemia	2/7 (28.6%)	2	1/10 (10%)	1
Leukopenia	1/7 (14.3%)	1	0/10 (0%)	0
Neutropenia	5/7 (71.4%)	6	0/10 (0%)	0
Cardiac disorders
Sinus tachycardia	1/7 (14.3%)	1	0/10 (0%)	0
Tachycardia	0/7 (0%)	0	1/10 (10%)	1
Ear and labyrinth disorders
Tinnitus	0/7 (0%)	0	1/10 (10%)	1
Eye disorders
Lacrimation increased	0/7 (0%)	0	1/10 (10%)	1
Photophobia	0/7 (0%)	0	1/10 (10%)	1
Photopsia	0/7 (0%)	0	1/10 (10%)	1
Vision blurred	0/7 (0%)	0	1/10 (10%)	1
Gastrointestinal disorders
Abdominal distension	0/7 (0%)	0	1/10 (10%)	1
Abdominal pain	1/7 (14.3%)	1	2/10 (20%)	3
Abdominal pain lower	0/7 (0%)	0	1/10 (10%)	1
Constipation	4/7 (57.1%)	4	1/10 (10%)	1
Diarrhoea	0/7 (0%)	0	1/10 (10%)	1
Dry mouth	0/7 (0%)	0	1/10 (10%)	1
Dyspepsia	1/7 (14.3%)	1	1/10 (10%)	1
Gingivitis	1/7 (14.3%)	1	0/10 (0%)	0
Nausea	6/7 (85.7%)	10	4/10 (40%)	5
Oral pain	0/7 (0%)	0	1/10 (10%)	1
Reflux oesophagitis	1/7 (14.3%)	1	0/10 (0%)	0
Vomiting	2/7 (28.6%)	4	1/10 (10%)	1
General disorders
Asthenia	1/7 (14.3%)	1	0/10 (0%)	0
Catheter related complication	1/7 (14.3%)	4	0/10 (0%)	0
Catheter site pain	0/7 (0%)	0	1/10 (10%)	1
Chest pain	1/7 (14.3%)	2	2/10 (20%)	2
Chills	0/7 (0%)	0	1/10 (10%)	1
Fatigue	5/7 (71.4%)	8	4/10 (40%)	5
Influenza like illness	1/7 (14.3%)	1	0/10 (0%)	0
Oedema peripheral	0/7 (0%)	0	1/10 (10%)	1
Performance status decreased	0/7 (0%)	0	1/10 (10%)	1
Temperature intolerance	0/7 (0%)	0	1/10 (10%)	1
Infections and infestations
Bronchitis	0/7 (0%)	0	1/10 (10%)	1
Gastroenteritis viral	0/7 (0%)	0	1/10 (10%)	1
Lymphadenitis bacterial	1/7 (14.3%)	1	0/10 (0%)	0
Pneumonia	1/7 (14.3%)	1	0/10 (0%)	0
Sinusitis	1/7 (14.3%)	1	0/10 (0%)	0
Urinary tract infection	0/7 (0%)	0	2/10 (20%)	2
Viral infection	0/7 (0%)	0	1/10 (10%)	1
Injury, poisoning and procedural complications
Contusion	0/7 (0%)	0	1/10 (10%)	1
Excoriation	1/7 (14.3%)	1	0/10 (0%)	0
Feeding tube complication	1/7 (14.3%)	1	0/10 (0%)	0
Investigations
Blood creatinine increased	1/7 (14.3%)	1	0/10 (0%)	0
Creatinine renal clearance decreased	0/7 (0%)	0	1/10 (10%)	1
Weight decreased	1/7 (14.3%)	1	0/10 (0%)	0
Metabolism and nutrition disorders
Anorexia	1/7 (14.3%)	1	2/10 (20%)	2
Decreased apetite	0/7 (0%)	0	1/10 (10%)	1
Dehydration	3/7 (42.9%)	3	1/10 (10%)	1
Hypercalcaemia	1/7 (14.3%)	2	0/10 (0%)	0
Hyperglycaemia	0/7 (0%)	0	1/10 (10%)	1
Hypokalemia	2/7 (28.6%)	2	1/10 (10%)	2
Hypomagnesaemia	1/7 (14.3%)	2	0/10 (0%)	0
Hyponatraemia	0/7 (0%)	0	1/10 (10%)	1
Hypophosphataemia	1/7 (14.3%)	1	0/10 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	1/7 (14.3%)	1	0/10 (0%)	0
Back pain	1/7 (14.3%)	1	2/10 (20%)	2
Muscular weakness	0/7 (0%)	0	1/10 (10%)	1
Musculoskeletal pain	0/7 (0%)	0	1/10 (10%)	2
Myalgia	1/7 (14.3%)	1	0/10 (0%)	0
Pain in extremity	0/7 (0%)	0	1/10 (10%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor associated fever	0/7 (0%)	0	1/10 (10%)	2
Nervous system disorders
Dizziness	1/7 (14.3%)	1	2/10 (20%)	3
Headache	2/7 (28.6%)	3	0/10 (0%)	0
Paraesthesia	1/7 (14.3%)	1	1/10 (10%)	2
Visual field defect	1/7 (14.3%)	1	0/10 (0%)	0
Psychiatric disorders
Anxiety	0/7 (0%)	0	1/10 (10%)	1
Depression	2/7 (28.6%)	2	2/10 (20%)	2
Renal and urinary disorders
Bladder pain	0/7 (0%)	0	1/10 (10%)	1
Bladder spasm	0/7 (0%)	0	1/10 (10%)	1
Hydronephrosis	1/7 (14.3%)	2	0/10 (0%)	0
Micturition urgency	0/7 (0%)	0	1/10 (10%)	1
Pollakiuria	0/7 (0%)	0	1/10 (10%)	1
Urinary incontinence	0/7 (0%)	0	2/10 (20%)	2
Reproductive system and breast disorders
Vaginal inflammation	1/7 (14.3%)	1	0/10 (0%)	0
Vulvovaginal dryness	0/7 (0%)	0	1/10 (10%)	1
Respiratory, thoracic and mediastinal disorders
Bronchospasm	0/7 (0%)	0	1/10 (10%)	1
Cough	2/7 (28.6%)	2	1/10 (10%)	1
Hypoxia	0/7 (0%)	0	1/10 (10%)	1
Increased upper airway secretion	0/7 (0%)	0	1/10 (10%)	1
Nasal dryness	1/7 (14.3%)	1	0/10 (0%)	0
Pharyngolaryngeal pain	1/7 (14.3%)	1	0/10 (0%)	0
Rhinitis allergic	0/7 (0%)	0	1/10 (10%)	1
Wheezing	0/7 (0%)	0	1/10 (10%)	1
Skin and subcutaneous tissue disorders
Alopecia	2/7 (28.6%)	2	1/10 (10%)	1
Dry skin	0/7 (0%)	0	1/10 (10%)	1
Hyperhidrosis	0/7 (0%)	0	1/10 (10%)	1
Night sweats	0/7 (0%)	0	1/10 (10%)	1

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.