MDACC Study Summary 2007-0688 (Archived)

Study Summary
No. 2007-0688:.......Melanoma......Merrick I. Ross......Surgical Oncology

Study Summary Title



Study Summary Number:	2007-0688

Study Title:	An Open-label, Multicenter, Phase 1/2 Dose Escalation Study to Evaluate Safety, Tolerability and Anti-tumor Activity of Systemic ADH-1 in Combination with Normothermic Isolated Limb Infusion of Melphalan in Subjects with Locally Advanced In-Transit Malignant Melanoma

Physician

New Patient Referral



Name:	Merrick I. Ross	Patients Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Dept:	Surgical Oncology	Referring MD Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Phone:	713-792-6940 Contact us about clinical trials

General Information



Disease Group:	Melanoma	Supported By:	Adherex Technologies, Inc

Phase of Study:	Phase I	Return Visit:	Patients must return for surgery which is when ILI will be preformed. Then every 3 months for 1 year post ILI and every 6 months for year 2 and 3 post ILI.

Treatment Agents:	ADH-1 Melphalan	Home Care:	N/A

Treatment Loc:	Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions

Estimated Length of Stay in Houston:	7-8 days for surgery and recovery.

Description/
Intervention:

The goal of this clinical research study is to find the highest tolerable dose
of ADH-1 given in combination with an isolated limb infusion (ILI) of melphalan
that can be given to patients with melanoma. The safety of these drugs will
also be studied. Another goal of the study is to find out what effects ADH-1
(study drug) in combination with Isolated Limb perfusion (ILI) of Melphalan has
on you in controlling your melanoma.

Study Objectives / Outcomes

Primary Objective
Phase I portion: To determine Dose-Limiting Toxicities (DLTs) and Maximum Tolerated Dose (MTD) of systemic ADH-1 in combination with regionally administered melphalan by isolated limb infusion (ILI).

Phase II portion: To assess antitumor activity according to unconfirmed RECIST modified for cutaneous lesions, as evidenced by best overall response by Week 12.

Secondary Objective
To characterize the safety and tolerability of systemic ADH-1 in combination with regionally administered melphalan ILI.

To assess antitumor activity according to unconfirmed Response Evaluation Criteria in Solid Tumors [RECIST] modified for cutaneous lesions, as evidenced by overall response at Week 6, best overall response at Week 6, best overall response by Month 6, and duration of response.

To characterize the duration of response and progression-free survival.

To characterize melphalan and ADH-1 pharmacokinetics.

To assess alterations in gene and protein expression profiles in tumors before and after study drug administration (biopsies will not be performed on target lesions used to define response).

Gene expression analysis will be conducted using an Affymetric Human Genome U133 +2 (HU133+2) and examinations will include (but are not limited to) genes involved in angiogenesis, cell cycle, and apoptosis;

Protein expression analysis will be conduced by immunohistochemistry (IHC) analysis and will examine protein profiles for N-and E-cadherin, Beta-catenin, DNA-melphalan adducts, and Ki-67.

Exploratory analyses of anti-tumor activity that consider only those tumors in-field will be conducted.

Primary Endpoint
Phase I: The MTD of systemic ADH-1 administered in combination with regionally administered melphalan via ILI, as measured by occurrence of DLTs.

Phase II: To tabulate the Best Overall Response by Week 12 according to unconfirmed RECIST, modified for cutaneous lesions, and to estimate the response (CR+PR) rate and its 90% exact binomial confidence interval.

Secondary Endpoint
Safety and tolerability of systemic ADH-1 administered in combination with regionally administered melphalan via ILI, assessed by the occurrence of adverse events (AEs), laboratory data, and other clinical data.

Tumor response in the Per Protocol Population assessed according to unconfirmed RECIST modified for cutaneous lesions.

Duration of tumor response.

Progression-free survival.

Assessment of melphalan and ADH-1 pharmacokinetics.

Gene and protein expression profiles in non-target lesion tumors before and after study drug administration and the relationship of these profiles to subject response.

Best Overall Response at Week 6, Week 12, and Month 6, considering only those tumors in-field.

Study Status Information



Study Activation / Registration Date:	12/20/2007

IRB Review and Approval Date:	12/20/2007

Study Type:	Phase I

Recruitment Status:	Terminated

Projected Accrual:	56

Enrollment Eligibility

If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:

1) Signed informed consent

2) Greater than or equal to 18 years of age

3) Histologically confirmed diagnosis of primary or recurrent Stage IIIB or IIIC extremity melanoma. American Joint Committee on Cancer (AJCC) staging must be documented in subject's medical record. NOTE: Any subject with an indeterminate staging must be reviewed by the Study Coordinating Investigator prior to registration

4) Subjects with Stage IIIC disease must have had regional lymph nodes previously removed prior to study drug administration

5) All subjects must have tissue available for N-cadherin staining by IHC. For subjects with a single lesion, archived tissue must be availabe for N-cadherin staining.

6) All disease site(s) must be distal to the planned site of tourniquet placement, which for the leg is generally the apex of the femoral triangle, or for the arm is distal to the deltoid insertion.

7) A palpable femoral or axillary pulse must be present in the affected extremity

8) Target lesions must be directly measurable by caliper (cutaneous lesions) or radiological method (non-cutaneous lesions) as defined by RECIST modified for cutaneous lesions. Additionally, photodocumentation is required.

9) Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

10) Adequate liver function: serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 2.5 x upper limit normal (ULN), AND serum bilirubin less than or equal to 1.5 x ULN

11) Adequate bone marrow function: absolute neutrophil count (ANC) of greater than or equal to 1.5 x 10 ^9/L; platelet count of greater than or equal to 100 x 10^9/L; AND hemoglobin greater than or equal to 10 g/dL

12) Adequate renal function: serum creatinine less than or equal to 1.5 x ULN

13) Recovery from relevant toxicity prior to first study drug administration

14) Adequate wound healing since the last major surgery

15) Negative serum or urine pregnancy test within 72 hours prior to study drug administration for women of childbearing potential. Effective contraception throughout the course of the study for both male and female subjects if the risk of conception exists

Exclusion Criteria:

1) Administration of ADH-1 prior to this clinical study; subject may have received prior melphalan via ILI

2) Antineoplastic therapy, radiotherapy, or any other investigational drug within 4 weeks prior to first study drug administration

3) Stage IV disease

4) History of tumors that have shown clinically significant evidence of active bleeding (e.g., gross hemoptysis, hematemesis, hematuria, melena, or bleeding superficial tumor) within 12 weeks prior to first study drug administration

5) History of other malignancies except: adequately treated basal or squamous cell carcinoma of the skin; curatively treated in situ carcinoma of the uterine cervix, prostate cancer, or superficial bladder cancer; or other solid tumors curatively treated with no evidence of disease for greater than or equal to 5 years

6) Stroke, major surgery, or other major tissue injury within 4 weeks prior to first study drug administration

7) Uncontrolled congestive heart failure (classified according to the New York Heart Association classification as having Class III or IV heart disease), coronary artery disease, or life-threatening arrhythmias; myocardial infarction less than 12 months prior to first study drug administration; significant electrocardiogram (ECG) abnormalities

8) Anticoagulant therapy within 7 days prior to first study drug administration, with the exception of low molecular weight heparin

9) Other uncontrolled serious chronic disease or conditions that in the investigator's opinion could render compliance or follow-up in the protocol problematic

10) Allergic reaction to any therapeutic peptide or to melphalan

11) Breast feeding or lactating

12) Unable to return at the regular required intervals for reassessment or study drug administration

13) Legal incapacity or limited legal capacity, unless authorization is granted by a legal guardian

Links

Registration Number: NCT00421811
Study Information on Clinical Trials Registry (clinicaltrials.gov)