GTI-2040 and Capecitabine in Treating Patients With Metastatic Breast Cancer

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00068588
• Collaborator: (none)
• Enrollment: 24
• Location: 1
• Arm: 1
• Duration (Months): 77
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This phase II trial is studying how well giving GTI-2040 together with capecitabine works in treating patients with metastatic breast cancer. Drugs used in chemotherapy, such as capecitabine, work in different ways to stop tumor cells from dividing so they stop growing or die. GTI-2040 may help capecitabine kill more tumor cells by making them more sensitive to the drug

Condition or Disease	Intervention/Treatment	Phase
Male Breast Cancer; Recurrent Breast Cancer; Stage IV Breast Cancer	Biological: GTI-2040; Drug: capecitabine	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To evaluate the response rate and response duration to combination therapy with GTI-2040 and capecitabine in the treatment of metastatic breast cancer.

2. To safely evaluate the toxicity of this drug combination and schedule in this patient population by first using a lower dose followed by escalation.

3. To determine pharmacokinetic data on plasma levels of GTI-2040 in this patient population.

4. To investigate potential molecular markers of ribonucleotide reductase inhibition and fluoropyrimidine metabolism in this patient population treated with the combination of GTI-2040 and capecitabine.

OUTLINE: This is a multicenter study.

Patients receive GTI-2040 IV continuously on days 1-15 of the first course and days 1-14 of all subsequent courses. Patients also receive oral capecitabine twice daily on days 2-15. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Study of GTI-2040 (NSC 722929) in Combination With Capecitabine in Metastatic Breast Cancer
• Study Start Date: Oct 1, 2003
• Actual Primary Completion Date: Mar 1, 2010
• Actual Study Completion Date: Mar 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (GTI-2040, capecitabine) Patients receive GTI-2040 IV continuously on days 1-15 of the first course and days 1-14 of all subsequent courses. Patients also receive oral capecitabine twice daily on days 2-15. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Biological: GTI-2040; Given IV; Drug: capecitabine; Given orally; Other Names: CAPE Ro 09-1978/000 Xeloda

Outcome Measures

Primary Outcome Measures

1. Maximum Tolerated Dose Determined by Dose-limiting Toxicities [21 days]

   1st 3 pts will be treated on arm 2. If 0/3 DLTs observed, the dose will be escalated to arm 3. If 1/3 DLTs onserved on arm 2, 3 more pts will be treated on arm 2. If no additional DLTs are observed on arm 2, the dose will be escalated to arm 3. If at most 1/6 DLTs observed on arm 3, arm 3 will be considered the MTD. If more than 1/6 DLTs observed on arm 3, the dose will be de-escalated to arm 2. If at most 1/6 DLTs observed on arm 2, arm 2 will be considered the MTD. If more than 1/6 pts on arm 2 experience a DLT, the dose will be de-escalated to arm 1. The remaining pts will be treated on arm 1 as the MTD, unless more than 1/6 DLTs, in which case the study will stop. DLT is defined as any grade III or IV non-hematologic toxicity (incl. diarrhea w\ adequate antidiarrheal treatment & hydration & nausea/vomiting w\ maximal antiemetic prophylaxis, as per protocol) or grade IV hematologic toxicity. DLT will be based on the 1st course of treatment according to the revised NCI CTC v 2.0

2. Response Rate of a Combination of GTI-2040 and Capecitabine [Up to 6 years]

   Following the dose escalation step, additional patients will be accrued at the MTD and evaluated for disease response using RECIST v1.0 criteria. Patients with confirmed complete or partial response are considered to have responded favorably to treatment.The sample size and early stopping for futility was governed by a two stage Optimum design suggested by Simon. It was assumed that a true response rate less than 25% would not warrant further study of this agent. It was also assumed that a response rate of 45% would be considered promising. In the first stage (following the dose escalation step), 15 evaluable patients were treated. Four or fewer observed responses, would stop accrual, while 5 or more observed would continue accrual for an additional 12 patients during the second stage of the study. Ten or more responses out of 27 patients will be considered evidence warranting further study of the regimen providing toxicity and survival also appear favorable.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed metastatic adenocarcinoma of the breast

• Patients must have measurable disease, defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral CT scan

• Patients must have progressed on at least one but no more than two prior chemotherapy regimens for metastatic disease; patients must not have received prior capecitabine or 5-fluorouracil; patients with hormone-sensitive tumors should have received hormone treatment and any prior number of hormonal agents will be allowed; patients with tumors that overexpress HER-2/neu (3+ by immunohistochemistry or amplified by fluorescent in situ hybridization) should have received herceptin, either in the adjuvant or metastatic setting, unless there is a contraindication to herceptin therapy; all prior therapies must have been completed 4 weeks before treatment

• Life expectancy of greater than 3 months

• ECOG performance status =< 2 (Karnofsky >= 50%)

• Leukocytes >= 3,000/μL

• Absolute neutrophil count >= 1,500/μL

• Platelets >= 100,000/μL

• Total bilirubin within normal institutional limits

• AST(SGOT)/ALT(SGPT) =< 2.5 X institutional upper limit of normal

• Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min

• Patients must have completed radiation treatment > 4 weeks prior to study entry; previously radiated area(s) must not be the only site of disease

• All major surgical procedures must be completed > 4 weeks prior to study entry; placement of vascular access device or tissue biopsy will not be considered major surgery

• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately

• Ability to understand and the willingness to sign a written informed consent document

• Patients must agree to the placement of a central venous catheter in order to receive the continuous infusion treatment

Exclusion Criteria:

• Patients with only non-measurable disease, defined as all other lesions, including small lesions (longest diameter < 20 mm with conventional techniques or < 10 mm with spiral CT scan) and truly non-measurable lesions, which include the following:

• bone lesions

• leptomeningeal disease

• ascites

• pleural/pericardial effusion

• inflammatory breast disease

• lymphangitis cutis/pulmonis

• abdominal masses that are not confirmed and followed by imaging techniques

• cystic lesions

• Patients who have had chemotherapy, hormone therapy, or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier

• Patients may not be receiving any other investigational agents; patients may not have received prior GTI-2040

• Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to GTI-2040 or to capecitabine or 5-fluorouracil

• Patients requiring anticoagulant therapy; low-dose anticoagulant (warfarin 1 mg per day) for the primary prophylaxis of venous catheter-associated thrombosis is permitted

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

• Pregnant women are excluded from this study because GTI-2040 and capecitabine have the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with GTI-2040 and capecitabine, breastfeeding should be discontinued if the mother is treated

• Because patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with GTI-2040 or other agents administered during the study; appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California Davis Cancer Center	Sacramento	California	United States	95817

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Helen Chew, City of Hope Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00068588
• Other Study ID Numbers: NCI-2012-02827; PHII-46; N01CM62209; CDR0000327757
• First Posted: Sep 11, 2003
• Last Update Posted: Oct 31, 2014
• Last Verified: Jan 1, 2013

• Additional relevant MeSH terms: Breast Neoplasms; Breast Neoplasms, Male; Capecitabine

Study Results

Participant Flow

Pre-assignment Detail	1st 3 pts treated on arm 2. If 0/3 DLTs, escalate to arm 3. If 1/3 DLTs on arm 2, 3 more pts on arm 2. If 1/6 DLTs on arm 2, escalate to arm 3.If at most 1/6 DLTs on arm 3, MTD declared. If more than 1/6 DLTs on arm 3, then de-escalated to arm 2. If at most 1/6 DLTs on arm 2, MTD declared. If more than 1/6 DLTs on arm 2, then de-escalate to arm 1.

Arm/Group Title	Arm 1	Arm 2	Arm 3
Arm/Group Description	Capecitabine 800 mg/m2 BID for 14 days on days 2-15 of each 21 day cycle +GTI-2040 civ infusion 185 mg/m2/day on days 1-15 of cycle 1 and days 1-14 of each subsequent cycle,	Capecitabine 1000 mg/m2 BID for 14 days on days 2-15 of each 21 day cycle +GTI-2040 civ infusion 185 mg/m2/day on days 1-15 of cycle 1 and days 1-14 of each subsequent cycle,	Capecitabine 1250 mg/m2 BID for 14 days on days 2-15 of each 21 day cycle +GTI-2040 civ infusion 185 mg/m2/day on days 1-15 of cycle 1 and days 1-14 of each subsequent cycle,
Period Title: Overall Study
STARTED	0	3	21
COMPLETED	0	3	17
NOT COMPLETED	0	0	4

Baseline Characteristics

Arm/Group Title	Arm 1	Arm 2	Arm 3	Total
Arm/Group Description	Capecitabine 800 mg/m2 BID for 14 days on days 2-15 of each 21 day cycle +GTI-2040 civ infusion 185 mg/m2/day on days 1-15 of cycle 1 and days 1-14 of each subsequent cycle,	Capecitabine 1000 mg/m2 BID for 14 days on days 2-15 of each 21 day cycle +GTI-2040 civ infusion 185 mg/m2/day on days 1-15 of cycle 1 and days 1-14 of each subsequent cycle,	Capecitabine 1250 mg/m2 BID for 14 days on days 2-15 of each 21 day cycle +GTI-2040 civ infusion 185 mg/m2/day on days 1-15 of cycle 1 and days 1-14 of each subsequent cycle,	Total of all reporting groups
Overall Participants	0	3	21	24
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	63	52	53
Gender (participants) [Number]
Female	3 Infinity	21 700%	24 114.3%
Male	0 NaN	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	3 Infinity	21 700%	24 114.3%

Outcome Measures

1. Primary Outcome

Title	Maximum Tolerated Dose Determined by Dose-limiting Toxicities
Description	1st 3 pts will be treated on arm 2. If 0/3 DLTs observed, the dose will be escalated to arm 3. If 1/3 DLTs onserved on arm 2, 3 more pts will be treated on arm 2. If no additional DLTs are observed on arm 2, the dose will be escalated to arm 3. If at most 1/6 DLTs observed on arm 3, arm 3 will be considered the MTD. If more than 1/6 DLTs observed on arm 3, the dose will be de-escalated to arm 2. If at most 1/6 DLTs observed on arm 2, arm 2 will be considered the MTD. If more than 1/6 pts on arm 2 experience a DLT, the dose will be de-escalated to arm 1. The remaining pts will be treated on arm 1 as the MTD, unless more than 1/6 DLTs, in which case the study will stop. DLT is defined as any grade III or IV non-hematologic toxicity (incl. diarrhea w\ adequate antidiarrheal treatment & hydration & nausea/vomiting w\ maximal antiemetic prophylaxis, as per protocol) or grade IV hematologic toxicity. DLT will be based on the 1st course of treatment according to the revised NCI CTC v 2.0
Time Frame	21 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1	Arm 2	Arm 3
Arm/Group Description	Capecitabine 800 mg/m2 BID for 14 days on days 2-15 of each 21 day cycle +GTI-2040 civ infusion 185 mg/m2/day on days 1-15 of cycle 1 and days 1-14 of each subsequent cycle,	Capecitabine 1000 mg/m2 BID for 14 days on days 2-15 of each 21 day cycle +GTI-2040 civ infusion 185 mg/m2/day on days 1-15 of cycle 1 and days 1-14 of each subsequent cycle,	Capecitabine 1250 mg/m2 BID for 14 days on days 2-15 of each 21 day cycle +GTI-2040 civ infusion 185 mg/m2/day on days 1-15 of cycle 1 and days 1-14 of each subsequent cycle,
Measure Participants	0	3	6
Number [Patients experiencing DLT]	0	0

2. Primary Outcome

Title	Response Rate of a Combination of GTI-2040 and Capecitabine
Description	Following the dose escalation step, additional patients will be accrued at the MTD and evaluated for disease response using RECIST v1.0 criteria. Patients with confirmed complete or partial response are considered to have responded favorably to treatment.The sample size and early stopping for futility was governed by a two stage Optimum design suggested by Simon. It was assumed that a true response rate less than 25% would not warrant further study of this agent. It was also assumed that a response rate of 45% would be considered promising. In the first stage (following the dose escalation step), 15 evaluable patients were treated. Four or fewer observed responses, would stop accrual, while 5 or more observed would continue accrual for an additional 12 patients during the second stage of the study. Ten or more responses out of 27 patients will be considered evidence warranting further study of the regimen providing toxicity and survival also appear favorable.
Time Frame	Up to 6 years

Outcome Measure Data

Analysis Population Description

Response Rate was only assessed at the determined MTD. Additional patients were accrued to determine treatment efficacy at the MTD.

Arm/Group Title	Arm 1	Arm 2	Arm 3
Arm/Group Description	Capecitabine 800 mg/m2 BID for 14 days on days 2-15 of each 21 day cycle +GTI-2040 civ infusion 185 mg/m2/day on days 1-15 of cycle 1 and days 1-14 of each subsequent cycle,	Capecitabine 1000 mg/m2 BID for 14 days on days 2-15 of each 21 day cycle +GTI-2040 civ infusion 185 mg/m2/day on days 1-15 of cycle 1 and days 1-14 of each subsequent cycle,	Capecitabine 1250 mg/m2 BID for 14 days on days 2-15 of each 21 day cycle +GTI-2040 civ infusion 185 mg/m2/day on days 1-15 of cycle 1 and days 1-14 of each subsequent cycle,
Measure Participants	0	0	15
Number [percentage of patients responding]	20

Adverse Events

Time Frame	Adverse event data was collected over a 5.5 year period in which patients were actively treated.
Adverse Event Reporting Description	There was one death six days after treatment stopped possibly related to treatment described as "somnolence/depressed level of consciousness". "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Arm/Group Title	Arm 2		Arm 3
Arm/Group Description	Capecitabine 1000 mg/m2 BID for 14 days on days 2-15 of each 21 day cycle +GTI-2040 civ infusion 185 mg/m2/day on days 1-15 of cycle 1 and days 1-14 of each subsequent cycle,		Capecitabine 1250 mg/m2 BID for 14 days on days 2-15 of each 21 day cycle +GTI-2040 civ infusion 185 mg/m2/day on days 1-15 of cycle 1 and days 1-14 of each subsequent cycle,
All Cause Mortality
	Arm 2		Arm 3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm 2		Arm 3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/3 (66.7%)		6/21 (28.6%)
Gastrointestinal disorders
Diarrhea	0/3 (0%)	0	2/21 (9.5%)	2
Nausea	0/3 (0%)	0	1/21 (4.8%)	1
Vomiting	0/3 (0%)	0	1/21 (4.8%)	1
General disorders
Fatigue	0/3 (0%)	0	1/21 (4.8%)	1
Infections and infestations
Catheter related infection	1/3 (33.3%)	1	0/21 (0%)	0
Infection NOS	1/3 (33.3%)	1	1/21 (4.8%)	1
Investigations
Aspartate aminotransferase increased	1/3 (33.3%)	1	1/21 (4.8%)	1
Metabolism and nutrition disorders
Dehydration	0/3 (0%)	0	1/21 (4.8%)	1
Hypercalcemia	0/3 (0%)	0	1/21 (4.8%)	1
Hypokalemia	0/3 (0%)	0	2/21 (9.5%)	2
Hypophosphatemia	1/3 (33.3%)	1	2/21 (9.5%)	2
Nervous system disorders
Depressed level of consciousness	0/3 (0%)	0	1/21 (4.8%)	2
Peripheral sensory neuropathy	1/3 (33.3%)	1	0/21 (0%)	0
Renal and urinary disorders
Urogenital disorder	0/3 (0%)	0	1/21 (4.8%)	1
Skin and subcutaneous tissue disorders
Skin disorder	1/3 (33.3%)	1	0/21 (0%)	0
Other (Not Including Serious) Adverse Events
	Arm 2		Arm 3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		21/21 (100%)
Blood and lymphatic system disorders
Hemoglobin decreased	2/3 (66.7%)	5	19/21 (90.5%)	64
Packed red blood cell transfusion	0/3 (0%)	0	1/21 (4.8%)	1
Cardiac disorders
Palpitations	0/3 (0%)	0	2/21 (9.5%)	2
Sinus tachycardia	0/3 (0%)	0	1/21 (4.8%)	1
Eye disorders
Conjunctival disorder	0/3 (0%)	0	2/21 (9.5%)	2
Vision blurred	0/3 (0%)	0	1/21 (4.8%)	1
Gastrointestinal disorders
Abdominal pain	1/3 (33.3%)	1	1/21 (4.8%)	1
Constipation	0/3 (0%)	0	3/21 (14.3%)	4
Diarrhea	2/3 (66.7%)	3	5/21 (23.8%)	9
Dyspepsia	1/3 (33.3%)	1	2/21 (9.5%)	3
Incontinence NOS	0/3 (0%)	0	1/21 (4.8%)	1
Mucositis oral	0/3 (0%)	0	4/21 (19%)	6
Nausea	2/3 (66.7%)	4	5/21 (23.8%)	6
Vomiting	2/3 (66.7%)	2	2/21 (9.5%)	2
General disorders
Chest pain	0/3 (0%)	0	3/21 (14.3%)	4
Fatigue	3/3 (100%)	7	16/21 (76.2%)	54
Fever	0/3 (0%)	0	3/21 (14.3%)	3
General symptom	1/3 (33.3%)	1	11/21 (52.4%)	11
Injection site reaction	1/3 (33.3%)	2	0/21 (0%)	0
Oedema NOS	0/3 (0%)	0	1/21 (4.8%)	1
Pain	0/3 (0%)	0	5/21 (23.8%)	8
Investigations
Activated partial thromboplastin time prolonged	0/3 (0%)	0	1/21 (4.8%)	1
Alanine aminotransferase increased	2/3 (66.7%)	4	14/21 (66.7%)	49
Alkaline phosphatase increased	1/3 (33.3%)	2	12/21 (57.1%)	37
Aspartate aminotransferase increased	2/3 (66.7%)	3	17/21 (81%)	82
Creatinine increased	1/3 (33.3%)	1	1/21 (4.8%)	2
Hypercholesterolemia	0/3 (0%)	0	1/21 (4.8%)	3
INR increased	0/3 (0%)	0	2/21 (9.5%)	3
Laboratory test abnormal	0/3 (0%)	0	1/21 (4.8%)	1
Leukocyte count decreased	0/3 (0%)	0	1/21 (4.8%)	2
Leukopenia	2/3 (66.7%)	5	16/21 (76.2%)	72
Lymphocyte count decreased	0/3 (0%)	0	1/21 (4.8%)	1
Lymphopenia	0/3 (0%)	0	11/21 (52.4%)	29
Neutrophil count decreased	2/3 (66.7%)	3	15/21 (71.4%)	57
	1/3 (33.3%)	2	2/21 (9.5%)	6
Platelet count decreased	0/3 (0%)	0	12/21 (57.1%)	48
Weight gain	0/3 (0%)	0	1/21 (4.8%)	2
Weight loss	0/3 (0%)	0	1/21 (4.8%)	1
Metabolism and nutrition disorders
Anorexia	0/3 (0%)	0	2/21 (9.5%)	2
Dehydration	0/3 (0%)	0	4/21 (19%)	4
Hyperglycemia	1/3 (33.3%)	1	12/21 (57.1%)	31
Hypernatremia	0/3 (0%)	0	2/21 (9.5%)	2
Hypoalbuminemia	0/3 (0%)	0	11/21 (52.4%)	19
Hypocalcemia	0/3 (0%)	0	13/21 (61.9%)	48
Hypoglycemia	0/3 (0%)	0	6/21 (28.6%)	6
Hypokalemia	1/3 (33.3%)	1	7/21 (33.3%)	14
Hyponatremia	0/3 (0%)	0	5/21 (23.8%)	6
Hypophosphatemia	0/3 (0%)	0	9/21 (42.9%)	35
Serum calcium increased	0/3 (0%)	0	1/21 (4.8%)	3
Serum phosphate decreased	0/3 (0%)	0	1/21 (4.8%)	2
Musculoskeletal and connective tissue disorders
Bone pain	1/3 (33.3%)	2	1/21 (4.8%)	1
Musculoskeletal disorder	1/3 (33.3%)	1	0/21 (0%)	0
Nervous system disorders
Dizziness	0/3 (0%)	0	2/21 (9.5%)	2
Peripheral sensory neuropathy	0/3 (0%)	0	3/21 (14.3%)	4
Taste alteration	1/3 (33.3%)	2	0/21 (0%)	0
Psychiatric disorders
Anxiety	0/3 (0%)	0	2/21 (9.5%)	3
Depression	0/3 (0%)	0	2/21 (9.5%)	2
Renal and urinary disorders
Protein urine positive	0/3 (0%)	0	1/21 (4.8%)	1
Urogenital disorder	0/3 (0%)	0	1/21 (4.8%)	1
Respiratory, thoracic and mediastinal disorders
Cough	0/3 (0%)	0	2/21 (9.5%)	2
Dyspnea	0/3 (0%)	0	7/21 (33.3%)	9
Hemorrhage nasal	0/3 (0%)	0	1/21 (4.8%)	1
Skin and subcutaneous tissue disorders
Alopecia	1/3 (33.3%)	1	1/21 (4.8%)	2
Dry skin	0/3 (0%)	0	2/21 (9.5%)	3
Hand-and-foot syndrome	0/3 (0%)	0	12/21 (57.1%)	55
Nail disorder	0/3 (0%)	0	2/21 (9.5%)	2
Pruritus	0/3 (0%)	0	2/21 (9.5%)	2
Rash desquamating	0/3 (0%)	0	2/21 (9.5%)	2
Skin discolouration	1/3 (33.3%)	1	1/21 (4.8%)	5
Skin disorder	1/3 (33.3%)	5	0/21 (0%)	0
Urticaria	0/3 (0%)	0	1/21 (4.8%)	1
Vascular disorders
Hypotension	0/3 (0%)	0	2/21 (9.5%)	2

Limitations/Caveats

In the first stage of the two stage Optimum design, following the dose escalation step, 3 of 15 patients responded for a response rate of 20%. A response rate of less than 25% would not warrant further study.

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.