Ziv-Aflibercept for Advanced Progressive Carcinoid Tumors

NCT01782443 | Completed Phase 2 Results DMC

• 1 other identifier: 12-456
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 3

Brief Summary

This research study is a Phase II clinical trial, which tests the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific cancer. "Investigational" means that the drug, Ziv-aflibercept, is being studied. It also means that the FDA has not yet approved Ziv-aflibercept for use in patients with your type of cancer. Every person has molecules in their bloodstream called vascular endothelial growth factors (VEGFs). These molecules help grow and sustain new blood vessels needed by the human body. Cancer tumors hijack this mechanism because they need new blod vessels and oxygen to grow. Ziv-aflibercept is an antibody. Antibodies are proteins that are produced naturally in our bodies and help to recognize foreign substances in our body. Ziv-aflibercept is a "targeted therapy" called a "VEGF Trap", that "traps" (binds) these VEGFs and prevents the cancer from using them to grow. Though Ziv-aflibercept has not yet been FDA approved for the treatment of carcinoid tumors, it has recently been approved for patients with treatment-resistant colorectal cancer. In this research study, we will use Ziv-aflibercept in combination with standard octreotide therapy to see if it slows the growth or spread of your carcinoid tumor. Standard octreotide (sandostatin) therapy is currently approved for treating symptoms of carcinoid tumors, such as those caused by carcinoid syndrome. Carcinoid syndrome is caused by hormones and other substances released by carcinoid tumors into the bloodstream. One of these secreted substances is serotonin, one of the body's natural chemical messengers. When excess serotonin secreted by the carcinoid tumors reaches the body's tissues, it is thought to cause diarrhea and redness (flushing) of the face, chest or back. Excess serotonin may also cause changes in the structure of the heart valves, which can impair the heart's function. Octreotide works by binding to receptors found on carcinoid tumors and prevents the release of hormones from the tumor.

Conditions

Carcinoid Tumor

Keywords

Progressive; Metastatic

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  To evaluate the progression-free survival (PFS) duration of patients with metastatic, unresectable, progressive carcinoid tumors treated with Ziv-aflibercept. Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) was used. Progressive Disease (PD) is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study with at least a 5 mm absolute increase in the sum of all lesions. The appearance of one or more new lesions denotes disease progression. Partial Response (PR) is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

  2 years

Secondary Outcomes (3)

• Evaluation of Disease Response

  2 years

• Evaluation of Biochemical Response - Number of Patients With Greater Than 50% Drop in Chromogranin A From Baseline

  2 years

• Biochemical Response - Number of Patients With Greater Than 50% Drop in 24hr Urine 5-HIAA From Baseline

  2 years

Study Arms (1)

Experimental Treatment Arm

EXPERIMENTAL

Ziv-aflibercept IV every 2 weeks, 4 mg/kg

Drug: Ziv-aflibercept

Interventions

Ziv-aflibercept DRUG

Experimental Treatment Arm

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed well differentiated or moderately differentiated neuroendocrine tumor from either a primary or metastatic site
• Must have disease that is not amenable to curative resection
• Must have evidence of disease progression within 12 months prior to study entry
• Must have measurable disease (RECIST 1.1)
• Prior chemoembolization of local ablative therapies are allowed, provided there is measurable disease outside of the area treated, or documented evidence of progression at the site of prior treatment
• No limit to number of prior treatments. Prior bevacizumab allowed unless discontinued due to unacceptable toxicity. Prior TKI targeting VEGF receptors allowed
• Treatment with a somatostatin analog required for all subjects
• Subjects with history of hypertension must be adequately controlled
• Therapeutic anticoagulation is allowed. Must be on a stable dose of anticoagulant medication
• Must agree to use adequate contraception prior to study entry, for the duration of study participation and for 3 months after last administration of study drug

You may not qualify if:

• Prior treatment including chemoembolization within 4 weeks of study entry
• Major surgery within 4 weeks of study entry or minor surgery within 2 weeks of study entry
• Pregnant or breastfeeding
• Poorly differentiated carcinoma, high grade neuroendocrine tumor or small cell carcinoma
• Prior treatment with Ziv-aflibercept
• Pancreatic neuroendocrine tumor (islet cell carcinoma)will be excluded from this study. All non functional and functional islet cell carcinomas such as insulinoma, glucagonoma, gastrinoma, VIPoma will be excluded.
• Not adequately recovered from toxicity of previous therapy
• Known untreated brain or other central nervous system metastases
• Known allergy to any of the study agents or to compounds of similar chemical or biologic composition
• History of congestive heart failure
• Symptomatic peripheral arterial disease
• Unhealed wounds, ulcers or bone fractures
• HIV positive or active Hepatitis infection
• History of abdominal fistula, GI perforation, intra abdominal abscess, uncontrolled GI bleeding, diverticulitis within 6 months of study entry
• History of arterial thrombotic events such as myocardial infarction, unstable angina pectoris or any ischemic or hemorrhagic cerebrovascular accident within the past 6 months

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead

Study Sites (3)

Massachusetts General Hospital

Boston, Massachusetts, 02115, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Related Publications (1)

• Perez K, Kulke MH, Horick NK, Regan E, Graham C, Scheutz S, Stonely D, Enzinger PC, Fuchs CS, Allen JN, Enzinger AC, Clark JW, Chan JA. A Phase II Study of Ziv-Aflibercept in Patients With Advanced Extrapancreatic Neuroendocrine Tumors. Pancreas. 2022 Aug 1;51(7):763-768. doi: 10.1097/MPA.0000000000002099.

  PMID: 36395401 DERIVED

MeSH Terms

Conditions

Carcinoid Tumor; Neoplasm Metastasis

Interventions

aflibercept

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Dr. Jennifer Chan
• Organization: DFCI

jang@partners.org

617-632-6315

Study Officials

• Jennifer Chan, MD

  Dana-Farber Cancer Institute

  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: PRINCIPAL INVESTIGATOR
• PI Title: Prinicipal Investigator

Study Record Dates

• First Submitted: January 31, 2013
• First Posted: February 1, 2013
• Study Start: February 13, 2013
• Primary Completion: March 1, 2021
• Study Completion: December 26, 2021
• Last Updated: August 14, 2023
• Results First Posted: November 9, 2022

Record last verified: 2023-08

Locations

US (3)