Clinical trial NCT00101972: RAV12 in Treating Patients With Metastatic or Recurrent Adenocarcinoma
Official title: A Phase I, Multi-Dose Study of RAV12 (ANTI-RAAG12 MAB) in Patients With Metastatic or Recurrent Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cancer
Keywords: 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
Lead sponsor: MacroGenics
Sponsor class: INDUSTRY
First posted: 2005-01-19
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Toxicity by CTCAE
timeFrame: Days 1-50
Secondary outcomes:
measure: Maximum tolerated dose
timeFrame: Days 1-50
measure: Pharmacokinetics of RAV12 by serum levels
timeFrame: Days 1, 2, 4, 5, 8, 15, 22, 29, 36, 43, and 50
measure: Immunogenicity by Human Anti-chimeric antibodies
timeFrame: Days 1, 8, 15, 22, and 50
measure: Time to tumor progression by clinical assessment
timeFrame: 6 months
measure: Progression free survival by clinical assessment
timeFrame: 3 and 6 months
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: Premiere Oncology
state: California
city: Washington
country: United States
facility: Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
state: District of Columbia
city: Miami
country: United States
facility: University of Miami Sylvester Comprehensive Cancer Center - Miami
state: Florida
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center - Philadelphia
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Cancer Center at Centennial Medical Center
state: Tennessee
Study officials:
References:
citation: 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.