Clinical trial NCT00005842: Trastuzumab Plus R115777 in Treating Patients With Advanced or Metastatic Cancer
Official title: A Phase I, Pharmacokinetic, and Biologic Correlative Study of R115777 (NSC 702818) and Herceptin in Patients With Advanced Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cancer
Keywords: stage III colon cancer
stage IV colon cancer
stage IV breast cancer
stage IIIA breast cancer
recurrent breast cancer
stage III gastric cancer
stage IV gastric cancer
recurrent gastric cancer
occult non-small cell lung cancer
stage IIIB breast cancer
recurrent non-small cell lung cancer
stage III pancreatic cancer
recurrent pancreatic cancer
stage III rectal cancer
stage IV rectal cancer
recurrent colon cancer
recurrent rectal cancer
stage IV anal cancer
recurrent anal cancer
stage III esophageal cancer
stage IV esophageal cancer
stage IIIA anal cancer
stage IIIB anal cancer
recurrent esophageal cancer
stage III cervical cancer
recurrent cervical cancer
stage IVB cervical cancer
stage IVA cervical cancer
inflammatory breast cancer
stage III renal cell cancer
stage IV renal cell cancer
recurrent renal cell cancer
metastatic parathyroid cancer
recurrent parathyroid cancer
stage III vulvar cancer
stage IVB vulvar cancer
recurrent vulvar cancer
stage III vaginal cancer
stage IVA vaginal cancer
stage IVB vaginal cancer
recurrent vaginal cancer
metastatic gastrointestinal carcinoid tumor
recurrent gastrointestinal carcinoid tumor
localized unresectable adult primary liver cancer
advanced adult primary liver cancer
recurrent adult primary liver cancer
gastrinoma
stage III endometrial carcinoma
stage IV endometrial carcinoma
recurrent endometrial carcinoma
small intestine adenocarcinoma
unresectable gallbladder cancer
recurrent gallbladder cancer
unresectable extrahepatic bile duct cancer
recurrent extrahepatic bile duct cancer
recurrent small intestine cancer
stage III adrenocortical carcinoma
stage IV adrenocortical carcinoma
recurrent adrenocortical carcinoma
stage III bladder cancer
recurrent bladder cancer
stage IV bladder cancer
stage III malignant testicular germ cell tumor
stage III prostate cancer
stage IV prostate cancer
recurrent prostate cancer
recurrent malignant testicular germ cell tumor
insulinoma
recurrent islet cell carcinoma
stage IV papillary thyroid cancer
stage IV follicular thyroid cancer
thyroid gland medullary carcinoma
anaplastic thyroid cancer
recurrent thyroid cancer
stage IIIA non-small cell lung cancer
stage IIIB non-small cell lung cancer
stage IV non-small cell lung cancer
stage III salivary gland cancer
stage IV salivary gland cancer
recurrent salivary gland cancer
WDHA syndrome
somatostatinoma
pancreatic polypeptide tumor
glucagonoma
stage III follicular thyroid cancer
stage III papillary thyroid cancer
recurrent urethral cancer
distal urethral cancer
proximal urethral cancer
urethral cancer associated with invasive bladder cancer
metastatic transitional cell cancer of the renal pelvis and ureter
pulmonary carcinoid tumor
stage III mucoepidermoid carcinoma of the oral cavity
stage III adenoid cystic carcinoma of the oral cavity
stage IV mucoepidermoid carcinoma of the oral cavity
stage IV adenoid cystic carcinoma of the oral cavity
recurrent mucoepidermoid carcinoma of the oral cavity
recurrent adenoid cystic carcinoma of the oral cavity
tumors metastatic to brain
lung metastases
liver metastases
bone metastases
skin metastases
leptomeningeal metastases
malignant pericardial effusion
malignant pleural effusion
newly diagnosed carcinoma of unknown primary
recurrent transitional cell cancer of the renal pelvis and ureter
carcinoma of the appendix
primary peritoneal cavity cancer
recurrent carcinoma of unknown primary
male breast cancer
stage IV pancreatic cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2004-04-26
Enrollment: 24
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: Phase I trial to study the effectiveness of trastuzumab plus R115777 in treating patients who have advanced or metastatic cancer. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining trastuzumab with R115777 may kill more tumor cells.

Detailed description: OBJECTIVES:

I. Determine the maximum tolerated dose of R115777 when administered with trastuzumab (Herceptin) in patients with advanced or metastatic adenocarcinoma.

II. Assess the toxicities and pharmacokinetics of this treatment regimen in this patient population.

III. Determine the antitumor activity of this treatment regimen in these patients.

IV. Determine the relative biologic endpoints of this regimen and correlate them with toxicity and pharmacokinetic parameters in these patients.

OUTLINE: This is a dose escalation, multicenter study of R115777.

Patients receive trastuzumab (Herceptin) IV over 90 minutes on days 1, 8, 15, and 22 plus oral R115777 twice daily for 3 weeks. Treatment continues every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of R115777 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which no more than 1 of 6 patients experiences dose limiting toxicities.

Patients are followed every 30 days until toxicity resolves.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed advanced or metastatic adenocarcinoma
* Expression of +1 to 3+ HER2/neu on immunohistochemical or immunocytochemistry staining
* No brain metastases unless all of the following is true:

  * Previously treated
  * Asymptomatic
  * Stable dose of decadron
* No evidence of edema

PATIENT CHARACTERISTICS:

* Age: 18 and over
* Performance status: ECOG 0-2
* Life expectancy: At least 12 weeks
* Absolute granulocyte count at least 1,500/mm3
* Platelet count at least 100,000/mm3
* Hemoglobin at least 9.0 g/dL
* Bilirubin no greater than 1.5 mg/dL
* AST/ALT no greater than 3 times upper limit of normal (ULN) (no greater than 5 times ULN in case of liver involvement)
* Creatinine no greater than 1.5 mg/dL
* LVEF at least 50% by RVG or MUGA
* No uncontrolled unstable angina
* No history of congestive heart failure or cardiac ischemia
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No concurrent active infection or serious systemic disorder that would preclude study
* No allergies to imidazole compounds

PRIOR CONCURRENT THERAPY:

* No prior trastuzumab (Herceptin) No other concurrent immunotherapy
* At least 4 weeks since prior chemotherapy (6 weeks since mitomycin or nitrosoureas) and recovered
* No other concurrent chemotherapy
* No concurrent hormonal cancer therapy except LHRH agonists for prostate cancer
* No concurrent radiotherapy
* No other concurrent experimental medications

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Fort Sam Houston
country: United States
facility: Brooke Army Medical Center
state: Texas
city: San Antonio
country: United States
facility: Institute for Drug Development
state: Texas
Study officials:
affiliation: San Antonio Cancer Institute
name: Anthony W. Tolcher, MD
role: STUDY_CHAIR
References:
citation: Schwartz G, Rowinsky EK, Rha SY, et al.: A phase I, pharmacokinetic, and biologic correlative study of R115777 and trastuzumab (herceptin) in patients with advanced cancer. [Abstract] Proceedings of the American Society of Clinical Oncology 20: A-322, 2001.