A Study of Cixutumumab (IMC-A12) in Islet Cell Cancer

NCT00781911 | Completed Phase 2 Results DMC

• 3 other identifiers: 13929CP13-0710I5A-IE-JAEE
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 10

Brief Summary

Determine the 6-month progression free survival (PFS) rate associated with cixutumumab in combination with depot octreotide acetate (octreotide) in participants with metastatic neuroendocrine tumors.

Conditions

Carcinoma; Neuroendocrine Tumors

Keywords

Islet Cell; CARCINOMA, ISLET CELL; Octreotide; depot octreotide acetate; Insulin-Like Growth Factor (IGF) 1; Metastatic, Carcinoid or Islet Cell; Neuroendocrine Tumors

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Progression-Free Survival (PFS) Rate at Six Months

  Percentage of participants who are alive and progression-free at 6 month from start of the study treatment over all participants. PFS is defined as the time from the start of study treatment until the date of objectively determined progressive disease (PD) or death due to any cause. Disease progression was assessed via Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0, and defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, and/or the appearance of one or more new lesion(s), and/or unequivocal progression of existing nontarget lesions. Participants without documentation of progression or death will be censored at the date of last tumor assessment. The PFS was estimated by the binomial distribution and Kaplan-Meier method.

  From Start of Study Treatment to Progressive Disease or Death Due to Any Cause (Up to 6 Months)

Secondary Outcomes (10)

• Percentage of Participants Who Achieve Modified Objective Response Rate (ORR) of Complete Response (CR), Partial Response (PR) and Minor Response (MR) Modified Objective Response Rate (mORR)

  From Start of Treatment Baseline to Disease Progression (Up to 18 Months)

• Percentage of Participants With a Biochemical Response Rate

  From Start of Treatment Up to 18 Months

• Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs)

  18 months

• Pharmacokinetics (PK): Maximum Concentration (Cmax) Cycle 1

  Prior to the final infusion, immediately after the infusion, and 1, 2, 4, 8, 48, 96, 168, and 336 hours after the completion of the final infusion

• PK: Half-life (t 1/2) Cycle 1

  Prior to the final infusion, immediately after the infusion, and 1, 2, 4, 8, 48, 96, 168, and 336 hours after the completion of the final infusion

Study Arms (2)

Carcinoid tumor

EXPERIMENTAL

Participants with carcinoid tumor will receive cixutumumab 10 mg/kg over 1 hour every 2 weeks. Treatment will continue until there is evidence of disease progression, intolerable toxicity, or other withdrawal criteria are met. Participants must be receiving depot octreotide at the time of enrolling into the study. Participants on stable doses of depot octreotide will continue to receive the same dose and schedule of their last regimen.

Biological: Cixutumumab; Drug: depot octreotide

Islet cell carcinoma

EXPERIMENTAL

Participants with islet cell carcinoma will receive cixutumumab 10 mg/kg over 1 hour every 2 weeks. Treatment will continue until there is evidence of disease progression, intolerable toxicity, or other withdrawal criteria are met. Participants must be receiving depot octreotide at the time of enrolling into the study. Participants on stable doses of depot octreotide will continue to receive the same dose and schedule of their last regimen.

Biological: Cixutumumab; Drug: depot octreotide

Interventions

Cixutumumab BIOLOGICAL

Participants will receive cixutumumab IV 10 mg/kg over 1 hour every 2 weeks. Treatment will continue until there is evidence of disease progression, intolerable toxicity, or other withdrawal criteria are met.

Also known as: IMC-A12, LY3012217

Carcinoid tumor; Islet cell carcinoma

depot octreotide DRUG

Participants must be receiving depot octreotide at the time of enrolling into the study. Participants on stable doses of depot octreotide will continue to receive the same dose and schedule of their last regimen.

Also known as: SMS 201-995

Carcinoid tumor; Islet cell carcinoma

Eligibility Criteria

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

You may qualify if:

• The participant has well-differentiated or moderately-differentiated, histologically confirmed neuroendocrine carcinoma, including carcinoid of any location and islet cell tumors
• The participant has metastatic disease at the time of study entry
• The participant must have a tumor measurable according to Response Evaluation Criteria in Solid Tumors (RECIST) guidelines, measurable by elevated tumor markers (eg, 24-hour urine 5-HIAA, chromogranin A, adrenocorticotropin hormone (ACTH), gastrin, or other tumor specific biochemical markers), or both
• The participant is age ≥ 18 years
• The participant's tumor has Ki-67 expression ≤ 20%
• The participant is receiving depot octreotide therapy at the time of enrolling into the study
• The participant has received 0 - 2 systemic anticancer regimens in addition to depot octreotide, which may have included chemotherapy, interferon, antiangiogenic therapy, other targeted treatments, or a combination of such treatments
• The participant is no longer a candidate for surgery, embolization, or radiofrequency ablation therapy
• The participant has experienced radiographic, biochemical, and/or scintigraphic disease progression while on a regimen that includes octreotide
• The participant has completed prior chemotherapy and/or radiotherapy with curative intent at least 3 weeks prior to the administration of the first dose of study therapy. Participants that have received palliative radiation therapy to bony metastases prior to the first dose of study medication are eligible
• The participant has a life expectancy of \> 3 months
• The participant has an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-2
• The participant has adequate hematologic function as defined by absolute neutrophil count ≥ 1500/microliters (μL), hemoglobin ≥ 9 gram/deciliter (g/dL), and platelet count ≥100,000/μL
• The participant has adequate hepatic function as defined by a total bilirubin ≤ 1.5 x the upper limit of normal (ULN), and aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x the ULN (or ≤ 5 x the ULN in the presence of known liver metastases)
• The participant either has adequate coagulation function as defined by international normalized ratio (INR) ≤ 1.5 and partial thromboplastin time (PTT) no more than 5 seconds above the ULN, or is on a stable dose of anticoagulant

You may not qualify if:

• The participant has uncontrolled brain or leptomeningeal metastases
• The participant has not recovered to Grade ≤ 1 from adverse events due to agents administered more than 4 weeks prior to study entry (except for alopecia)
• The participant is receiving any other investigational agent(s)
• The participant has received therapeutic radiolabeled somatostatin analogues
• The participant has received more than 2 prior regimens of systemic therapy in the metastatic setting
• The participant has a history of treatment with other agents targeting the IGF receptor
• The participant has a history of allergic reactions attributed to compounds of chemical or biologic composition similar to that of cixutumumab or to octreotide
• The participant has poorly controlled diabetes mellitus. Participants with a history of diabetes mellitus are allowed to participate, provided that their fasting glucose \< 160 mg/dL or below the ULN and that they are on a stable dietary or therapeutic regimen for this condition
• The participant has an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics, symptomatic congestive heart failure, uncontrolled hypertension, clinically significant cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• The participant is pregnant or lactating
• The participant is known to be positive for infection with the human immunodeficiency virus
• The participant has a history of another primary cancer, with the exception of: a) curatively resected nonmelanomatous skin cancer; b) curatively treated cervical carcinoma in-situ; or c) other primary solid tumor curatively resected or treated with no known active disease present and no treatment administered for the last 3 years

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (10)

ImClone Investigational Site

Los Angeles, California, 90033, United States

Location

ImClone Investigational Site

Los Angeles, California, 90095, United States

Location

ImClone Investigational Site

Aurora, Colorado, 80045, United States

Location

ImClone Investigational Site

Atlanta, Georgia, 30318, United States

Location

ImClone Investigational Site

Indianapolis, Indiana, 46202, United States

Location

ImClone Investigational Site

Kenner, Louisiana, 70065, United States

Location

ImClone Investigational Site

Columbus, Ohio, 43210, United States

Location

ImClone Investigational Site

Providence, Rhode Island, 02903, United States

Location

ImClone Investigational Site

Nashville, Tennessee, 37232, United States

Location

ImClone Investigational Site

Dallas, Texas, 75246, United States

Location

MeSH Terms

Conditions

Carcinoma; Neuroendocrine Tumors; Carcinoma, Islet Cell; Neoplasm Metastasis; Carcinoid Tumor

Interventions

cixutumumab; Octreotide

Condition Hierarchy (Ancestors)

Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Adenocarcinoma; Pancreatic Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

800-545-5979

Study Officials

• Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2008
• First Posted: October 29, 2008
• Study Start: February 1, 2009
• Primary Completion: July 1, 2011
• Study Completion: May 1, 2016
• Last Updated: September 20, 2019
• Results First Posted: April 18, 2018

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
• Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.

Locations

US (10)