RAV12 in Treating Patients With Metastatic or Recurrent Adenocarcinoma

February 4, 2022 updated by: MacroGenics

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

53

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Santa Monica, California, United States, 90404
        • Premiere Oncology
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
    • Florida
      • Miami, Florida, United States, 33136
        • University of Miami Sylvester Comprehensive Cancer Center - Miami
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19111-2497
        • Fox Chase Cancer Center - Philadelphia
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Sarah Cannon Cancer Center at Centennial Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Toxicity by CTCAE
Time Frame: Days 1-50
Days 1-50

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

MacroGenics

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2004

Primary Completion (Actual)

May 1, 2008

Study Completion (Actual)

May 1, 2008

Study Registration Dates

First Submitted

January 18, 2005

First Submitted That Met QC Criteria

January 18, 2005

First Posted (Estimate)

January 19, 2005

Study Record Updates

Last Update Posted (Actual)

February 22, 2022

Last Update Submitted That Met QC Criteria

February 4, 2022

Last Verified

February 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000415581
  • RAVENBIO-RV-2004-002 (Other Identifier: Raven biotechnologies (MacroGenics))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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