RAV12 in Treating Patients With Metastatic or Recurrent Adenocarcinoma

Sponsor

MacroGenics (Industry)

Overall Status

Completed

CT.gov ID

NCT00101972

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

10.6

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Monoclonal antibodies, such as RAV12, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them.

PURPOSE: This phase I trial is studying the side effects and best dose of RAV12 in treating patients with metastatic or recurrent adenocarcinoma.

Condition or Disease	Intervention/Treatment	Phase
Cancer	Biological: monoclonal antibody RAV12	Phase 1

Detailed Description

OBJECTIVES:

Determine the maximum tolerated dose of RAV12 in patients with metastatic or recurrent adenocarcinoma.
Determine the toxicity profile of this drug in these patients.
Determine the pharmacokinetics and immunogenicity of this drug in these patients.
Determine, preliminarily, the antitumor activity of this drug in these patients.

OUTLINE: This is an open-label, dose-escalation study.

Patients receive RAV12 IV over 2 hours 2-3 times per week in weeks 1-4 (course 1). Patients are evaluated for response on day 43. Patients achieving a partial or complete response may be eligible to receive additional courses of RAV12 as above. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of RAV12 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Up to 15 additional patients are treated at the MTD in 1 or more patients groups (e.g., colorectal, pancreatic, gastroesophageal, and other adenocarcinoma).

After completion of study treatment, patients are followed within 4 weeks and then every 6-12 months thereafter.

PROJECTED ACCRUAL: A total of 75 patients will be accrued for this study.

Study Design

Study Type:

Interventional

Actual Enrollment :

53 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I, Multi-Dose Study of RAV12 (ANTI-RAAG12 MAB) in Patients With Metastatic or Recurrent Adenocarcinoma

Study Start Date :

Dec 1, 2004

Actual Primary Completion Date :

May 1, 2008

Actual Study Completion Date :

May 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: RAV12	Biological: monoclonal antibody RAV12 Escalating doses of RAV12 (weekly 0.3, 1.0, 1.5, 3.0, 4.0, 5.0, 6.0 mg/kg or 0.5 mg/kg BIW or TIW; 0.75 mg/kg BIW) for 4 weeks

Arm

Intervention/Treatment

Experimental: RAV12

Biological: monoclonal antibody RAV12

Escalating doses of RAV12 (weekly 0.3, 1.0, 1.5, 3.0, 4.0, 5.0, 6.0 mg/kg or 0.5 mg/kg BIW or TIW; 0.75 mg/kg BIW) for 4 weeks

Outcome Measures

Primary Outcome Measures

Toxicity by CTCAE [Days 1-50]

Secondary Outcome Measures

Maximum tolerated dose [Days 1-50]
Pharmacokinetics of RAV12 by serum levels [Days 1, 2, 4, 5, 8, 15, 22, 29, 36, 43, and 50]
Immunogenicity by Human Anti-chimeric antibodies [Days 1, 8, 15, 22, and 50]
Time to tumor progression by clinical assessment [6 months]
Progression free survival by clinical assessment [3 and 6 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed adenocarcinoma
Metastatic or recurrent disease
Not curable by standard therapies
Must have failed at least 1, but no more than 3, prior therapies for metastatic or recurrent disease
Patients with colorectal or breast adenocarcinoma must have failed at least 2 prior therapies
Must have had at least stable disease for 3 months while on last treatment prior to most recent disease progression
Meets 1 of the following criteria:
At least 1 measurable site of disease ≥ 2 cm by radiography
Evaluable disease that could be reliably and consistently followed, as deemed by the principal investigator
RAAG12 expression confirmed* by immunohistochemistry NOTE: *Not required for patients with colon, pancreatic, or gastric adenocarcinoma
No evidence of residual or recurrent CNS metastases
Hormone receptor status:
Not specified

PATIENT CHARACTERISTICS:

Age

18 and over

Sex

Not specified

Menopausal status

Not specified

Performance status

ECOG 0-1

Life expectancy

More than 3 months

Hematopoietic

Platelet count ≥ 100,000/mm^3
Hemoglobin ≥ 9.0 g/dL (transfusions allowed)
Absolute neutrophil count ≥ 1,500/mm^3

Hepatic

Bilirubin ≤ 1.5 times upper limit of normal (ULN)
AST and ALT ≤ 2.5 times ULN
Alkaline phosphatase ≤ 2.5 times ULN
γ-glutamyl transferase ≤ 2.5 times ULN
Adequate hepatic function sufficient to undergo study therapy

Renal

Creatinine < 1.5 mg/dL
Adequate renal function sufficient to undergo study therapy

Cardiovascular

No New York Heart Association class III or IV heart disease
No thrombosis within the past 3 months, including any of the following:
Deep vein thrombosis
Myocardial infarction
Stroke
Adequate cardiac function sufficient to undergo study therapy

Pulmonary

No pulmonary embolism within the past 3 months
No significant pulmonary compromise, particularly dependence on supplemental oxygen on an as-needed or continuous basis
Adequate pulmonary function sufficient to undergo study therapy

Immunologic

No active viral, bacterial or systemic fungal infection requiring parenteral therapy within the past 4 weeks
No history of chronic or recurrent infection requiring continual antiviral, antifungal, or antibacterial agents
No known hypersensitivity to murine or recombinant proteins, polysorbate 80, or any excipient contained in study drug

Other

Amylase and lipase normal
No other primary malignancy within the past 3 years except for the following:
Treated non-melanoma skin cancer
Carcinoma in situ of the cervix by biopsy
Squamous intraepithelial lesion of the cervix by PAP smear
Localized prostate cancer (Gleason score < 6)
Resected melanoma in situ
No other serious medical condition that would preclude study participation
No dementia or altered mental status that would preclude giving informed consent
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 3 months after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

At least 3 half-lives since prior monoclonal antibody therapy
No concurrent vaccinations
No concurrent prophylactic hematologic growth factors

Chemotherapy

At least 4 weeks since prior chemotherapy

Endocrine therapy

No concurrent steroids except for the following:
Inhaled, ophthalmic, or nasal steroids
Stable dose of oral prednisone (or equivalent) ≤ 10 mg/day

Radiotherapy

At least 4 weeks since prior radiotherapy

Surgery

More than 4 weeks since prior major surgery

Other

More than 4 weeks since prior investigational agents
Prior oral antiviral, antifungal, or antibacterial therapy allowed provided therapy was completed within the past week
No other concurrent antineoplastic therapy
No concurrent immunosuppressive medications
No other concurrent investigational agents
No concurrent vitamins except those approved by the medical monitor
Concurrent daily multivitamin allowed
Concurrent bisphosphonates allowed provided patient is on stable dose for ≥ 1 month prior to study entry

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Premiere Oncology	Santa Monica	California	United States	90404
2	Lombardi Comprehensive Cancer Center at Georgetown University Medical Center	Washington	District of Columbia	United States	20007
3	University of Miami Sylvester Comprehensive Cancer Center - Miami	Miami	Florida	United States	33136
4	Fox Chase Cancer Center - Philadelphia	Philadelphia	Pennsylvania	United States	19111-2497
5	Sarah Cannon Cancer Center at Centennial Medical Center	Nashville	Tennessee	United States	37203