Neoplasms

All Conditions

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Carcinoma

Neuroendocrine Tumors

Carcinoid Tumor

Carcinoma, Islet Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Neuroendocrine Tumor

Neuroepithelioma

Hypoglycemic Agents

All Drugs and Chemicals

Antineoplastic Agents

Gastrointestinal Agents

Insulin

Insulin, Globin Zinc

Mitogens

Octreotide

Antineoplastic Agents, Hormonal

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.

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.

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.

Cixutumumab

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.

depot octreotide

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)

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.

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

A Phase 2, Multicenter, Two Tier Study of IMC-A12 in Combination With Depot Octreotide in Patients With Metastatic, Well or Moderately Differentiated Carcinoid or Islet Cell Carcinoma

Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

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.

Modified ORR is defined as CR+ PR + MR. According to RECIST v1.0, CR was defined as the disappearance of all target and non-target lesions; PR defined as a \>30% decrease in the sum of the longest diameters (LD) of the target lesions, taking as reference the baseline sum of the LD and MR defined as 20% - 29% reduction. Disease progression 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.

Determine the biochemical response rate (≥ 50% reduction in tumor-specific markers; may include, not limited to 24 hour urine 5-hydroxyindoleacetic acid, chromogranin A, adrenocorticotropin hormone (ACTH), or gastrin) in the subset of participants with biochemically measurable disease.

Number of participants that had at least one TEAE is presented. A summary of other non-serious adverse events and all serious adverse events, regardless of causality, is located in the Reported Adverse Events Section.

Eli Lilly and Company

Participants with carcinoid tumor received cixutumumab 10 mg/kg IV over 1 hour every 2 weeks. Treatment continued 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 continued to receive the same dose and schedule of their last regimen.

Participants with islet cell carcinoma received cixutumumab 10 mg/kg IV over 1 hour every 2 weeks. Treatment continued 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 continued to receive the same dose and schedule of their last regimen.

Islet Cell Carcinoma

Participants received cixutumumab 10 mg/kg IV over 1 hour every 2 weeks. Treatment continued 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 continued to receive the same dose and schedule of their last regimen.

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Chief Medical Officer

Binomial Distribution; Primary Analysis

Kaplan-Meier Method; Secondary Analysis

Participants with islet cell carcinoma received cixutumumab 10 mg/kg IV over 1 hour every 2 weeks. Treatment continued 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 continued to receive the same dose and schedule of their last regimen.

All participants who received at least one dose of study drug. Participants censored in the carcinoid tumor arm were 8 and in the islet cell carcinoma arm were 4.

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

All participants who received at least one dose of study drug.

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)

Chromogranin A

Gastrin

All participants who received at least one dose of study drug and had evaluable baseline and post-baseline Chromogranin A and Gastrin data.

Percentage of Participants With a Biochemical Response Rate

Participants with islet cell carcinoma received cixutumumab 10 mg/kg IV over 1 hour every 2 weeks. Treatment continued 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 continued to receive the same dose and schedule of their last regimen.

All participants who had received at least one dose of study drug.

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

Zero participants were analyzed. The assay used to measure serum concentrations of cixutumumab was not fully developed and validated, and the resulting data was therefore not suitable for estimation of PK parameters.

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

PK: Half-life (t 1/2) Cycle 1

PK: Area Under Concentration (AUCinf) Cycle 1

PK: Clearance (CL) Cycle 1

PK: Volume at Steady State (Vss) Cycle 1

Zero participants were analyzed due to no data collection due to low number of clinical responses observed.

Serum Anti-Cixutumumab Antibody Assessment

Pharmacodynamics Markers; Concentration of Insulin-like Growth Factor I, II (IGF-I, IGF-II), IGF Body Fat (IGFBF)-1 and IGFBF-2

Participants with carcinoid tumor received cixutumumab 10 mg/kg intravenously (IV) over 1 hour every 2 weeks. Treatment continued 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 continued to receive the same dose and schedule of their last regimen.

Overall Study

Adenoma

Adenoma, Islet Cell

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Adenocarcinoma

Pancreatic Neuroendocrine Tumor

Pancreatic Cancer

Sunitinib

Angiogenesis Inhibitors

Growth Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

* sunitinib malate oral starting dose 37.5 mg daily (continuous dosing).
* Dose may be decreased to 25 mg daily in case of adverse events.
* It may be increased to 50 mg daily if no response is seen after 8 weeks on treatment.
* Dosing to continue until unacceptable toxicity, progression of disease, death, or study termination.

sunitinib malate

Placebo to match sunitinib taken daily (oral) on the same schedule as active agent below.

Placebo

Pfizer CT.gov Call Center

This study randomized patients with advanced pancreatic islet cell tumors to receive either sunitinib or placebo. Patients who were randomized to sunitinib received 37.5 mg of sunitinib daily, those randomized to placebo received a tablet that looked similar but had no active drug. Neither the patient or the doctor knew whether the patient was receiving sunitinib or placebo. Patients were followed to determine the status and size of their tumors, survival, quality of life and safety of the drug.

The study was designed to detect a 50% improvement in median PFS\[Progression Free Survival\] with 90% power and was to enroll 340 subjects. An interim analysis was planned when 130 events had occurred, and the final analysis was to be conducted when 260 events had occurred.

Study A6181111 was stopped early during the enrollment period because of a clear and clinically meaningful improvement in efficacy for the sunitinib treatment arm as recommended by the DMC \[Data Monitoring Committee\]. The actual number of subjects enrolled was 171 and the actual number of PFS events recorded was 81 PFS events. The decision to terminate the study was not based on safety concerns related to sunitinib administration.

The study was terminated on 11 March 2009 because the independent Data Monitoring Committee determined that the study had met its primary endpoint in demonstrating improvement in progression-free survival. The decision to terminate the trial was not based on safety concerns related to sunitinib administration.

A Study Of Sunitinib Compared To Placebo For Patients With Advanced Pancreatic Islet Cell Tumors

A Phase III Randomized, Double-Blind Study Of Sunitinib (SU011248, SUTENT) Versus Placebo In Patients With Progressive Advanced/Metastatic Well-Differentiated Pancreatic Islet Cell Tumors

Time from randomization to first progression of disease (PD) or death for any reason in the absence of documented PD. PFS was calculated as (first event date minus first randomization date +1) divided by 30.4.

Objective response = subjects with confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) for at least 4 weeks, confirmed by repeat tumor assessments. A CR was defined as the disappearance of all target lesions. A PR was defined as a \> = 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.

Time in months from the first documentation of objective tumor response to objective tumor progression or death due to any cause. DR was calculated as (the date of the first documentation of objective tumor progression or death due to any cause minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 30.4.

Time from randomization to the first documentation of objective tumor response (CR or PR) that was subsequently confirmed.

Time in months from time of randomization to date of death due to any cause. The median number of months is provided; however, the study was terminated early. OS data was not mature by the time of analysis. Median OS time cannot be accurately estimated by Kaplan-Meier method for either treatment arm.

EORTC QLQ-C30 scales: global health/QoL, functional domains (physical, role, cognitive, emotional, social), and symptom scales/items (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea). Recall period: past week; response range: not at all to very much, global/QOL range: very poor to excellent. Scale score range: 0 to 100. Higher functional/global QoL score = better functioning and higher symptom score = greater degree of symptoms.

Pfizer

Director, Clinical Trial Disclosure Group

Oral sunitinib 37.5 mg once daily on a continuous daily dosing schedule.

Between 18 and 44 years

Between 45 and 64

>=65 years

Age, Customized

Pfizer ClinicalTrials.gov Call Center

Intent-to-treat (ITT) population = all subjects who were randomized.

Progression Free Survival (PFS)

ITT. No placebo subjects had objective response.

Number of Subjects With Objective Response

ITT. DR was calculated for the subgroup of subjects with objective response. 8 sunitinib subjects reported CR or PR response and were analyzed for DR; no placebo subjects reported CR or PR.

Duration of Response (DR)

ITT. TTR was calculated for the subgroup of subjects with objective response. 8 sunitinib subjects reported CR or PR response and were analyzed for TTR; no placebo subjects reported CR or PR.

Time-to-Tumor Response (TTR)

ITT. The median OS in months could not be calculated for placebo.

Overall Survival (OS)

Cycle 1 (n=66, 66)

Cycle 2 (n=68, 66)

Cycle 3 (n=60, 56)

Cycle 4 (n=55, 43)

Cycle 5 (n=48, 40)

Cycle 6 (n=42, 31)

Cycle 7 (n=37, 28)

Cycle 8 (n=33, 22)

Cycle 9 (n=33, 18)

Cycle 10 (n=29, 14)

Patient Reported Outcome (PRO) population=subjects from the ITT population who had completed at least 1 EORTC QLQ-C30 assessment while on treatment. n=number of subjects with EORTC QLQ-C30 score at each specified time point. Data in cycles beyond Cycle 10 are not reported due to few subjects and lack of statistical reliability.

European Organization for Research and Treatment of Cancer Quality of LifeQuestionnaire (EORTC QLQ-C30) - Global Quality of Life (QoL) Subscale

Cycle 1 (n=67, 66)

Cycle 2 (n=69, 66)

Cycle 7 (n=38, 28)

Cycle 8 (n=34, 22)

PRO population. n=number of subjects with EORTC QLQ-C30 score at each specified time point. Data in cycles with less than 10 subjects are not reported due to lack of statistical reliability.

EORTC QLQ-C30 - Cognitive Functioning Subscale

PRO population. n=number of subjects with EORTC QLQ-C30 score at each specified time point. Data in cycles beyond Cycle 10 are not reported due to few subjects and lack of statistical reliability.

EORTC QLQ-C30 - Emotional Functioning Subscale

Cycle 2 (n=69, 67)

Cycle 6 (n=42, 30)

EORTC QLQ-C30 - Physical Functioning Subscale

Cycle 5 (n=48, 41)

EORTC QLQ-C30 - Role Functioning Subscale

EORTC QLQ-C30 - Social Functioning Subscale

Cycle 8 (n=34, 21)

EORTC QLQ-C30 - Appetite Loss Subscale

Cycle 1 (n=67, 65)

Cycle 3 (n=59, 56)

Cycle 9 (n=32, 18)

EORTC QLQ-C30 - Constipation Subscale

Cycle 5 (n=47, 40)

EORTC QLQ-C30 - Diarrhea Subscale

EORTC QLQ-C30 - Dyspnea Subscale

EORTC QLQ-C30 - Fatigue Subscale

Cycle 2 (n=68, 65)

EORTC QLQ-C30 - Financial Difficulties Subscale

EORTC QLQ-C30 - Insomnia Subscale

EORTC QLQ-C30 - Nausea and Vomiting Subscale

EORTC QLQ-C30 - Pain Subscale

Oral sunitinib 37.5 milligrams (mg) once daily on a continuous daily dosing schedule.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Cixutumumab (IMC-A12) in Islet Cell Cancer	NCT00781911	Carcinoma Neuroendocrine ...	Cixutumumab depot octreotid...	18 Years -	Eli Lilly and Company
A Study Of Sunitinib Compared To Placebo For Patients With Advanced Pancreatic Islet Cell Tumors	NCT00428597	Carcinoma, Isle... Carcinoma, Panc...	sunitinib malat... Placebo	18 Years -	Pfizer
A Study of BBI608 in Combination With Standard Chemotherapies in Adult Patients With Pancreatic Cancer	NCT02231723	Metastatic Panc...	BBI608 Nab-paclitaxel Gemcitabine Oxaliplatin Leucovorin Irinotecan Fluorouracil MM-398	18 Years -	Sumitomo Pharma America, Inc.

Spots Global Cancer Trial Database for carcinoma, islet cell