Romidepsin in Treating Patients With Locally Advanced or Metastatic Neuroendocrine Tumors

National Cancer Institute (NCI)

Status and phase

Terminated

Phase 2

Conditions

Glucagonoma

Pancreatic Polypeptide Tumor

Regional Gastrointestinal Carcinoid Tumor

Insulinoma

Metastatic Gastrointestinal Carcinoid Tumor

Recurrent Islet Cell Carcinoma

Somatostatinoma

Pulmonary Carcinoid Tumor

Recurrent Gastrointestinal Carcinoid Tumor

Gastrinoma

Treatments

Drug: romidepsin

Other: laboratory biomarker analysis

Study type

Interventional

Funder types

NIH

Identifiers

NCT00084461

CDR0000365313

OSU-2003C0085

NCI-2012-01449

U01CA076576 (U.S. NIH Grant/Contract)

0425

NCI-6325

Details and patient eligibility

About

Phase II trial to study the effectiveness of romidepsin in treating patients who have locally advanced or metastatic neuroendocrine tumors. Drugs used in chemotherapy, such as romidepsin, work in different ways to stop tumor cells from dividing so they stop growing or die.

Full description

PRIMARY OBJECTIVES:

I. Determine objective response rate in patients with locally advanced or metastatic neuroendocrine tumors treated with FR901288 (romidepsin).

SECONDARY OBJECTIVES:

I. Determine the toxicity of this drug in these patients. II. To measure serum tumor markers (pancreastatin, gastrin, pancreatic polypeptide, glucagon, substance-P, neurotensin, calcitonin, somatostatin, vasoactive intestinal peptide, gastrin releasing polypeptide, ACTH) depending on the tumor type pre-, during-, and post-treatment.

III. To perform a nuclear medicine functional imaging scan (octreoscan) to evaluate the disease status pre-, during-, and post-treatment.

IV. To perform histone acetylation assay in cytospins from peripheral blood mononuclear cells (PBMCs) to correlate with disease response and with immunologic parameters.

V. To quantify gene expression by Real Time PCR of type 1 and type 2 cytokines, co-stimulatory molecules, and adhesion molecules in PBMCs obtained from the pre-, during-, and post-treatment blood samples.

VI. To perform a multicolor flow cytometric analysis on fresh blood to assess activation of lymphocyte subsets and presence of co-stimulatory and adhesion molecules.

VII. To perform in vitro functional assays for innate as well as antigen-specific T cell immune responses in PBMCs obtained from the pre-, during-, and post-treatment blood samples.

OUTLINE:

Patients receive romidepsin IV over 4 hours on days 1, 8, and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients achieving complete remission (CR) receive 2 additional courses beyond CR.

Patients are followed at 2-4 weeks.

Enrollment

25 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

Histologically confirmed carcinoid tumor or islet cell neuroendocrine tumor
- Well- or moderately-differentiated tumor
Metastatic and/or locally advanced disease
Measurable disease
- Unidimensionally measurable lesion at least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan
- Lesions in a previously irradiated area are not considered measurable
- No truly non-measurable lesions, including the following:
  - Bone lesions
  - Leptomeningeal disease
  - Ascites
  - Pleural or pericardial effusion
  - Lymphangitis cutis/pulmonis
  - Abdominal masses not confirmed and followed by imaging
  - Cystic lesions
Ineligible for standard treatment
Performance status - ECOG 0-1
At least 6 months
WBC >= 3,000/mm^3
Absolute neutrophil count >= 1,500/mm^3
Platelet count >= 100,000/mm^3
Bilirubin =< 1.5 mg/dL
AST and ALT =< 2.5 times upper limit of normal
Creatinine =< 1.5 mg/dL
No New York Heart Association class III or IV congestive heart failure
No myocardial infarction within the past year
No uncontrolled dysrhythmias
No poorly controlled angina
No serious ventricular arrhythmia, defined as ventricular tachycardia or ventricular fibrillation >= 3 beats in a row
No left ventricular hypertrophy by EKG
No other significant cardiac disease
QTc < 500 msec
LVEF > 40% by resting MUGA
No prior allergic reaction attributed to compounds of similar chemical or biological composition to study drug
No ongoing or active infection
No psychiatric illness or social situation that would preclude study compliance
No other concurrent uncontrolled illness
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
More than 4 weeks since prior immunotherapy (e.g., interferon alfa)
More than 4 weeks since prior chemotherapy
More than 12 weeks since prior hepatic artery chemoembolization unless liver lesions are not the only indicator lesions
No prior FR901228 (depsipeptide)
No more than 1 prior systemic chemotherapy regimen for carcinoid or islet cell tumor (other than hepatic artery chemoembolization)
More than 4 weeks since prior oral or IV steroids (first 16 patients only)
Concurrent long-acting octreotide allowed at standard doses if dose has been stable for the past 12 weeks
- Concurrent subcutaneous octreotide for breakthrough use for symptomatic relief allowed
No concurrent systemic steroids (first 16 patients only)
More than 4 weeks since prior radiotherapy
More than 4 weeks since prior investigational tumor-specific therapy
No other prior histone deacetylase inhibitors (e.g., valproic acid)
No concurrent hydrochlorothiazide
No concurrent combination antiretroviral therapy for HIV-positive patients
No other concurrent investigational or commercial agents or therapies for the malignancy