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

Phase 1
18 Years
Not Enrolling

Thank you

Trial Information

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


- Determine the maximum tolerated dose of RAV12 in patients with metastatic or recurrent

- 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

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.

Inclusion Criteria


- 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



- 18 and over


- Not specified

Menopausal status

- Not specified

Performance status

- ECOG 0-1

Life expectancy

- More than 3 months


- Platelet count ≥ 100,000/mm^3

- Hemoglobin ≥ 9.0 g/dL (transfusions allowed)

- Absolute neutrophil count ≥ 1,500/mm^3


- 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


- Creatinine < 1.5 mg/dL

- Adequate renal function sufficient to undergo study therapy


- 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


- 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


- 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


- 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


Biologic therapy

- At least 3 half-lives since prior monoclonal antibody therapy

- No concurrent vaccinations

- No concurrent prophylactic hematologic growth factors


- 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


- At least 4 weeks since prior radiotherapy


- More than 4 weeks since prior major surgery


- 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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Toxicity by CTCAE

Outcome Time Frame:

Days 1-50

Safety Issue:


Principal Investigator

Stanford J Stewart, MD

Investigator Role:

Study Director

Investigator Affiliation:



United States: Food and Drug Administration

Study ID:




Start Date:

December 2004

Completion Date:

May 2008

Related Keywords:

  • Cancer
  • adenocarcinoma of the bladder
  • adenocarcinoma of the colon
  • adenocarcinoma of the esophagus
  • adenocarcinoma of the extrahepatic bile duct
  • adenocarcinoma of the gallbladder
  • adenocarcinoma of the lung
  • adenocarcinoma of the pancreas
  • adenocarcinoma of the prostate
  • adenocarcinoma of the rectum
  • adenocarcinoma of the stomach
  • adenocarcinoma with squamous metaplasia of the gallbladder
  • cervical adenocarcinoma
  • endometrial adenocarcinoma
  • ovarian endometrioid adenocarcinoma
  • ovarian undifferentiated adenocarcinoma
  • salivary gland adenocarcinoma
  • small intestine adenocarcinoma
  • vaginal adenocarcinoma
  • vaginal clear cell adenocarcinoma
  • ovarian clear cell cystadenocarcinoma
  • ovarian mucinous cystadenocarcinoma
  • ovarian serous cystadenocarcinoma
  • stage IV bladder cancer
  • stage IV breast cancer
  • stage IV colon cancer
  • stage IV endometrial carcinoma
  • stage IV esophageal cancer
  • stage IV gastric cancer
  • stage IV non-small cell lung cancer
  • stage IV ovarian epithelial cancer
  • stage IV prostate cancer
  • stage IV rectal cancer
  • stage IV renal cell cancer
  • stage IV salivary gland cancer
  • stage IVA cervical cancer
  • stage IVA vaginal cancer
  • stage IVB cervical cancer
  • stage IVB vaginal cancer
  • recurrent bladder cancer
  • recurrent breast cancer
  • recurrent cervical cancer
  • recurrent colon cancer
  • recurrent endometrial carcinoma
  • recurrent esophageal cancer
  • recurrent extrahepatic bile duct cancer
  • recurrent gallbladder cancer
  • recurrent gastric cancer
  • recurrent non-small cell lung cancer
  • recurrent ovarian epithelial cancer
  • recurrent pancreatic cancer
  • recurrent prostate cancer
  • recurrent rectal cancer
  • recurrent renal cell cancer
  • recurrent salivary gland cancer
  • recurrent small intestine cancer
  • recurrent vaginal cancer
  • unresectable extrahepatic bile duct cancer
  • unresectable gallbladder cancer
  • stage IV pancreatic cancer
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous



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