RAV12 in Treating Patients With Metastatic or Recurrent Adenocarcinoma

NCT ID: NCT00101972

Last Updated: 2022-02-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 53 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-12-31
• Study Completion Date: 2008-05-31

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.

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.

Conditions

Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

RAV12

Group Type: EXPERIMENTAL

monoclonal antibody RAV12

Intervention Type: BIOLOGICAL

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

Interventions

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

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

MacroGenics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Premiere Oncology

Santa Monica, California, United States

Lombardi Comprehensive Cancer Center at Georgetown University Medical Center

Washington D.C., District of Columbia, United States

University of Miami Sylvester Comprehensive Cancer Center - Miami

Miami, Florida, United States

Fox Chase Cancer Center - Philadelphia

Philadelphia, Pennsylvania, United States

Sarah Cannon Cancer Center at Centennial Medical Center

Nashville, Tennessee, United States

Countries

United States

References

Burris HA 3rd, Rosen LS, Rocha-Lima CM, Marshall J, Jones S, Cohen RB, Kunkel LA, Loo D, Baughman J, Stewart SJ, Lewis N. Phase 1 experience with an anti-glycotope monoclonal antibody, RAV12, in recurrent adenocarcinoma. Clin Cancer Res. 2010 Mar 1;16(5):1673-81. doi: 10.1158/1078-0432.CCR-09-2263. Epub 2010 Feb 23.

Reference Type: RESULT

PMID: 20179219 (View on PubMed)

Other Identifiers

RAVENBIO-RV-2004-002

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000415581

Identifier Type: -

Identifier Source: org_study_id