Capecitabine and Temozolomide for Neuroendocrine Cancers

NCT00869050 | Completed Phase 2 Results DMC

• 1 other identifier: AAAP4117
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II study is designed to assess whether treatment with capecitabine/temozolomide (CAP/TEM) is safe and effective in treating subjects with progressive, differentiated, metastatic neuroendocrine tumors (NET). The primary objective of the study is to determine the radiologic response rate to this regimen in progressive, metastatic, differentiated neuroendocrine cancers.

Conditions

Neuroendocrine Tumors

Keywords

Pancreatic cancer; Neuroendocrine tumors; Carcinoid tumors; Pheochromocytomas; Gastrinomas; Zollinger-Ellison syndrome; MEN Type I/II; Somatostatinomas; VIPomas; Merkel cell tumors; medullary thyroid carcinoma

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Partial Response (PR)

  PR according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria, which is defined as a reduction of ≥ 30% in the sum of the longest diameter for all target lesions lasting \> 4 weeks, during which no new lesions may appear, when compared with with pretreatment measurements.

  12 months

• Number of Participants With Complete Response (CR)

  CR according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria, which is defined as disappearance of all target lesions (primary and metastases), signs, symptoms, and biochemical changes related to the tumor for \>4 weeks, during which no new lesions may appear and no existing lesion may enlarge.

  12 months

Study Arms (1)

Capecitabine and Temozolomide

EXPERIMENTAL

Capecitabine 1500 mg/m2/day (PO divided BID) with a maximum daily dose of 2500mg and Temozolomide 150-200 mg/m2/day (PO divided BID).

Drug: Capecitabine; Drug: Temozolomide

Interventions

Capecitabine DRUG

Capecitabine 1500 mg/m2/day (PO divided BID) with a maximum daily dose of 2500mg Two week treatment regimen followed by two weeks off treatment, repeated for 12 cycles After patients have completed 12 cycles with no signs of progression of disease, radiologic evaluation (CT or MRI) will be done after three cycles. This will result in two 28 day cycles and one 35 day cycle.

Also known as: Xeloda

Capecitabine and Temozolomide

Temozolomide DRUG

Temozolomide 150-200 mg/m2/day (PO divided BID). Two week treatment regimen followed by two weeks off treatment, repeated for 12 cycles After patients have completed 12 cycles with no signs of progression of disease, radiologic evaluation (CT or MRI) will be done after three cycles. This will result in two 28 day cycles and one 35 day cycle.

Also known as: Temodar

Capecitabine and Temozolomide

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have a tissue diagnosis of any of the following metastatic, well or moderately differentiated, slow growing neuroendocrine tumor and must demonstrate progressive metastatic disease by prior serial computerized tomography (CT) or magnetic resonance imaging (MRI) scans, or have increased symptoms from their tumors while on sandostatin LAR or octreotide.
• Carcinoid tumors originating anywhere in the body including the gastrointestinal (GI) tract or bronchial tree
• Pancreatic neuroendocrine tumors (including functional and non-functional islet cell, insulinomas and glucagonomas)
• Pheochromocytomas, gastrinomas (Zollinger-Ellison Syndrome), multiple endocrine neoplasia (MEN) Type I/II, paragangliomas, adrenal carcinomas with NET markers by immunohistochemistry (IHC) or serum.
• Somatostatinoma, VIPoma, Merkel Cell tumors, medullary thyroid carcinoma
• Neuroendocrine tumors of unknown primary site
• Any other tumors with differentiated neuroendocrine features may be included such as aggressive pituitary adenomas/carcinomas, which are neuroendocrine in origin
• Patients must have progressed on octreotide therapy (up to and including Sandostatin LAR-60 mg/month) and/or radioactive isotopes linked to octreotide or its congeners if they has a positive octreotide scan. Patients who have negative or mildly positive octreotide scans are exempt from this requirement. Exceptions to this requirement are patients who have NETs in the pituitary gland. Sandostatin does not cross into the pituitary blood supply well.
• Measurable disease: Any primary and/or metastatic mass reproducibly measurable in one or two diameters by Response Evaluation Criteria In Solid Tumors (RECIST) parameters by CT scan or MRI scan.
• Ineligible for other high priority national or institutional studies
• Prior radiation and surgery allowed: ≥3 weeks since surgery or chemotherapy or hepatic embolization/chemoembolization or radioactive isotopes (i.e. Yttrium 90) ≥4 weeks since radiation therapy (RT)
• Non pregnant females, not in menopause, who are not breast feeding with a negative serum β-HCG (human chorionic gonadotropin) test within 1 week of starting the study. Men and women of childbearing potential must consent to using effective barrier contraception while on treatment and for 2 months thereafter.

You may not qualify if:

• Prior chemotherapy with capecitabine or temozolomide. Patients previously treated with continuous infusion 5-FU or any schedule of DTIC (dacarbazine), which are similar to capecitabine and temozolomide, respectively, will be excluded. Patients can have had prior therapies up to 3 prior chemotherapy regimens such as bolus 5-FU, streptozocin, anthracyclines, Camptothecin-11 (CPT-11), etoposide, or a platinum agent
• Hypersensitivity: Patients with a history of severe hypersensitivity reaction to capecitabine, 5-FU, temozolomide or DTIC will be excluded (i.e. anaphylaxis or anaphylactoid reactions)
• Serious medical or psychiatric illness preventing informed consent or intensive treatment (e.g, serious infection)
• Patients with tumor which has spread to the central brain (cerebral/cerebellum) and spinal cord.
• Patients with compromised immune systems are at increased risk of toxicity and lethal infections when treated with marrow-suppressive therapy. Therefore, HIV-positive patients are excluded from the study
• Prior malignancies in the last 5 years other than; curatively treated carcinoma in-situ previously treated with curative intent (cancer free for the past year)

Sponsors & Collaborators

• Columbia University: lead

Study Sites (1)

Columbia University Medical Center

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Neuroendocrine Tumors; Pancreatic Neoplasms; Carcinoid Tumor; Pheochromocytoma; Gastrinoma; Zollinger-Ellison Syndrome; Somatostatinoma; Vipoma; Carcinoma, Medullary

Interventions

Capecitabine; Temozolomide

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Paraganglioma; Carcinoma, Islet Cell; Paraneoplastic Endocrine Syndromes; Paraneoplastic Syndromes; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Peptic Ulcer; Duodenal Diseases; Intestinal Diseases; Stomach Diseases; Carcinoma, Neuroendocrine; Neoplasms, Ductal, Lobular, and Medullary

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles

Results Point of Contact

• Title: Dr. Paul Oberstein
• Organization: Columbia University

po2178@cumc.columbia.edu

212-305-0592

Study Officials

• Paul E Oberstein, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2009
• First Posted: March 25, 2009
• Study Start: August 1, 2005
• Primary Completion: December 1, 2013
• Study Completion: October 1, 2014
• Last Updated: July 25, 2016
• Results First Posted: June 22, 2016

Record last verified: 2016-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)