AMG 479 in Advanced Carcinoid and Pancreatic Neuroendocrine Tumors

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ClinicalTrials.gov Identifier: NCT01024387

Recruitment Status : Completed

First Posted : December 2, 2009

Results First Posted : December 27, 2017

Last Update Posted : March 8, 2018

Sponsor:

Collaborators:

Brigham and Women's Hospital

Massachusetts General Hospital

H. Lee Moffitt Cancer Center and Research Institute

Amgen

Information provided by (Responsible Party):

Matthew H. Kulke, MD, Dana-Farber Cancer Institute

Study Type	Interventional
Study Design	Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Conditions	Neuroendocrine Tumor Carcinoid Tumor Pancreatic Neuroendocrine Tumor
Intervention	Drug: AMG 479
Enrollment	60

Participant Flow

Recruitment Details	Patients enrolled from June 2010 through June 2011.
Pre-assignment Details


Arm/Group Title	AMG 479
Arm/Group Description	Patients receive AMG 479 at a dose ...
Arm/Group Description	Patients receive AMG 479 at a dose of 18 mg/kg administered IV on day 1 (± 3 days) of every 3-week cycle. Treatment should continue until disease progression, unacceptable toxicity or withdrawal of consent.
Period Title: Overall Study
Started	60
Evaluable for PFS ^[1]	54
Evaluable for Response ^[2]	53
Completed ^[3]	0
Not Completed	60
Reason Not Completed
Radiographic Progression	29
Symptomatic Progression	10
Physician Decision	5
Withdrawal by Subject	5
Death	2
Prolonged Treatment Delay	1
Adverse Event	3
Other	5
[1] One of the patients uneval for resp was incl in PFS eval dataset which included follow-up for death. [2] symptomatic deterioration (n=2), patient or MD decision (n=2 each), hypersensitivity reaction (n=1) [3] Given treatment duration is not fixed, all patients are considered as 'Non Completed'.

Baseline Characteristics

Arm/Group Title		AMG 479
Arm/Group Description		Patients receive AMG 479 at a dose ...
Arm/Group Description		Patients receive AMG 479 at a dose of 18 mg/kg administered IV on day 1 (± 3 days) of every 3-week cycle. Treatment should continue until disease progression, unacceptable toxicity or withdrawal of consent.
Overall Number of Baseline Participants		60
Baseline Analysis Population Description		...
Baseline Analysis Population Description		The analysis dataset is comprised of all enrolled patients.
Age, Continuous Median (Full Range) Unit of measure: Years
	Number Analyzed	60 participants
		61 (30 to 82)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	60 participants
	Female	38 63.3%
	Male	22 36.7%
Region of Enrollment Measure Type: Count of Participants Unit of measure: Participants
United States	Number Analyzed	60 participants
United States		60 100.0%

Outcome Measures

1.Primary Outcome


Title	Objective Response Rate
Description	Objective response rate is the percentage of patients achieving partia...
Description	Objective response rate is the percentage of patients achieving partial response (PR) or complete response (CR) per RECIST 1.0 criteria. For target lesions, CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. CR or PR status must be confirmed by repeat assessments performed no fewer than 4 weeks or more than 6 weeks after the response criteria are first met. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.
Time Frame	Disease was evaluated radiologically at baseline, every 3 cycles (9 weeks) on treatment and at end of treatment. Patients in this study cohort received a median of 6 treatment cycles (18 weeks).

Outcome Measure Data

Analysis Population Description

The analysis dataset is comprised of all response evaluable patients.


Arm/Group Title	AMG 479
Arm/Group Description:	Patients receive AMG 479 at a dose ...
Arm/Group Description:	Patients receive AMG 479 at a dose of 18 mg/kg administered IV on day 1 (± 3 days) of every 3-week cycle. Treatment should continue until disease progression, unacceptable toxicity or withdrawal of consent.
Overall Number of Participants Analyzed	53
Measure Type: Number Unit of Measure: percentage of patients
	0.0

2.Secondary Outcome


Title	Duration of Response
Description	The duration of response is measured from the time measurement criteri...
Description	The duration of response is measured from the time measurement criteria are met for CR/PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).
Time Frame	Disease was evaluated radiologically at baseline, every 3 cycles (9 weeks) on treatment and at end of treatment. Patients in this study cohort received a median of 6 treatment cycles (18 weeks).

Outcome Measure Data

Analysis Population Description

This endpoint was not evaluated because zero patients achieved objected response per RECIST criteria.


Arm/Group Title	AMG 479
Arm/Group Description:	Patients receive AMG 479 at a dose ...
Arm/Group Description:	Patients receive AMG 479 at a dose of 18 mg/kg administered IV on day 1 (± 3 days) of every 3-week cycle. Treatment should continue until disease progression, unacceptable toxicity or withdrawal of consent.
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

3.Secondary Outcome


Title	Grade 3-4 Toxicity Rate
Description	Grade 3-4 toxicity rate is the percentage of patients who experienced ...
Description	Grade 3-4 toxicity rate is the percentage of patients who experienced a grade 3 or 4 adverse event with treatment attribution of possible, probable or definite based on CTCAEv4.
Time Frame	Toxicity was evaluated every cycle (3 weeks) on treatment. Patients in this study cohort received a median of 6 treatment cycles (18 weeks).

Outcome Measure Data

Analysis Population Description

The analysis dataset is comprised of all enrolled patients.


Arm/Group Title	AMG 479
Arm/Group Description:	Patients receive AMG 479 at a dose ...
Arm/Group Description:	Patients receive AMG 479 at a dose of 18 mg/kg administered IV on day 1 (± 3 days) of every 3-week cycle. Treatment should continue until disease progression, unacceptable toxicity or withdrawal of consent.
Overall Number of Participants Analyzed	60
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of patients
	31.7 (22.3 to 45.0)

4.Secondary Outcome


Title	Progression Free Survival
Description	Progression-free survival (PFS) based on the Kaplan-Meier method is de...
Description	Progression-free survival (PFS) based on the Kaplan-Meier method is defined as the time from the start of treatment to the date of the first documented disease progression or death due to any cause. Patients without an event were censored at the earliest date of last disease assessment or initiation of non-protocol anti-cancer therapy. Per RECIST 1.0 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.
Time Frame	Disease was evaluated radiologically at baseline, every 3 cycles (9 weeks) on treatment and at end of treatment. Patients in this study cohort were followed up to 20 months.

Outcome Measure Data

Analysis Population Description

The analysis dataset is comprised of all PFS evaluable patients.


Arm/Group Title	AMG 479
Arm/Group Description:	Patients receive AMG 479 at a dose ...
Arm/Group Description:	Patients receive AMG 479 at a dose of 18 mg/kg administered IV on day 1 (± 3 days) of every 3-week cycle. Treatment should continue until disease progression, unacceptable toxicity or withdrawal of consent.
Overall Number of Participants Analyzed	54
Median (95% Confidence Interval) Unit of Measure: months
	6.3 (4.2 to 12.6)

5.Secondary Outcome


Title	1-Year Overall Survival
Description	Overall survival (OS) based on the Kaplan-Meier method is defined as t...
Description	Overall survival (OS) based on the Kaplan-Meier method is defined as the time from treatment start to the date of death or censored at the date last known alive. 1-year overall survival is the probability (%) of remaining alive 1 year from the start of treatment.
Time Frame	Patients in this study cohort were followed up to 20 months.

Outcome Measure Data

Analysis Population Description

The analysis dataset is comprised of all enrolled patients.


Arm/Group Title	AMG 479
Arm/Group Description:	Patients receive AMG 479 at a dose ...
Arm/Group Description:	Patients receive AMG 479 at a dose of 18 mg/kg administered IV on day 1 (± 3 days) of every 3-week cycle. Treatment should continue until disease progression, unacceptable toxicity or withdrawal of consent.
Overall Number of Participants Analyzed	60
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percent probability
	66 (52 to 77)

Adverse Events

Time Frame	Adverse events (AEs) were evaluated every cycle (3 weeks) on treatment. Patients in this study cohort received a median of 6 treatment cycles (18 weeks).
Adverse Event Reporting Description	Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.

Arm/Group Title	AMG 479
Arm/Group Description	Patients receive AMG 479 at a dose ...
Arm/Group Description	Patients receive AMG 479 at a dose of 18 mg/kg administered IV on day 1 (± 3 days) of every 3-week cycle. Treatment should continue until disease progression, unacceptable toxicity or withdrawal of consent.
All-Cause Mortality
	AMG 479
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events Serious Adverse Events
	AMG 479
	Affected / at Risk (%)
Total	19/60 (31.67%)
Blood and lymphatic system disorders
Anemia ^† 1	1/60 (1.67%)
Gastrointestinal disorders
Abdominal pain ^† 1	2/60 (3.33%)
General disorders
Death NOS ^† 1	1/60 (1.67%)
Infusion related reaction ^† 1	1/60 (1.67%)
Infections and infestations
Lung infection ^† 1	2/60 (3.33%)
Infections and infestations - Other, specify ^† 1	2/60 (3.33%)
Investigations
Alkaline phosphatase increased ^† 1	3/60 (5.00%)
Lymphocyte count decreased ^† 1	4/60 (6.67%)
Neutrophil count decreased ^† 1	2/60 (3.33%)
Platelet count decreased ^† 1	3/60 (5.00%)
Metabolism and nutrition disorders
Anorexia ^† 1	1/60 (1.67%)
Hyperglycemia ^† 1	9/60 (15.00%)
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	1/60 (1.67%)
Myalgia ^† 1	1/60 (1.67%)
† Indicates events were collected by systematic assessment 1 Term from vocabulary, CTCAE (4.0)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	AMG 479
	Affected / at Risk (%)
Total	57/60 (95.00%)
Blood and lymphatic system disorders
Anemia ^† 1	21/60 (35.00%)
Febrile neutropenia ^† 1	1/60 (1.67%)
Leukocytosis ^† 1	1/60 (1.67%)
Spleen disorder ^† 1	1/60 (1.67%)
Cardiac disorders
Atrial flutter ^† 1	1/60 (1.67%)
Chest pain - cardiac ^† 1	1/60 (1.67%)
Palpitations ^† 1	4/60 (6.67%)
Ear and labyrinth disorders
Hearing impaired ^† 1	1/60 (1.67%)
Ear and labyrinth disorders - Other, specify ^† 1	1/60 (1.67%)
Endocrine disorders
Cushingoid ^† 1	1/60 (1.67%)
Eye disorders
Blurred vision ^† 1	1/60 (1.67%)
Dry eye ^† 1	1/60 (1.67%)
Eye disorders - Other, specify ^† 1	1/60 (1.67%)
Gastrointestinal disorders
Abdominal distension ^† 1	5/60 (8.33%)
Abdominal pain ^† 1	22/60 (36.67%)
Anal pain ^† 1	2/60 (3.33%)
Ascites ^† 1	1/60 (1.67%)
Bloating ^† 1	3/60 (5.00%)
Cecal hemorrhage ^† 1	1/60 (1.67%)
Colitis ^† 1	3/60 (5.00%)
Colonic obstruction ^† 1	1/60 (1.67%)
Constipation ^† 1	13/60 (21.67%)
Diarrhea ^† 1	15/60 (25.00%)
Dry mouth ^† 1	4/60 (6.67%)
Duodenal hemorrhage ^† 1	1/60 (1.67%)
Dyspepsia ^† 1	3/60 (5.00%)
Dysphagia ^† 1	1/60 (1.67%)
Flatulence ^† 1	6/60 (10.00%)
Gastric fistula ^† 1	1/60 (1.67%)
Gastritis ^† 1	1/60 (1.67%)
Gastroesophageal reflux disease ^† 1	2/60 (3.33%)
Gastrointestinal pain ^† 1	1/60 (1.67%)
Hemorrhoidal hemorrhage ^† 1	1/60 (1.67%)
Hemorrhoids ^† 1	1/60 (1.67%)
Ileus ^† 1	1/60 (1.67%)
Lower gastrointestinal hemorrhage ^† 1	3/60 (5.00%)
Malabsorption ^† 1	1/60 (1.67%)
Mucositis oral ^† 1	3/60 (5.00%)
Nausea ^† 1	21/60 (35.00%)
Obstruction gastric ^† 1	1/60 (1.67%)
Pancreatitis ^† 1	1/60 (1.67%)
Rectal fistula ^† 1	1/60 (1.67%)
Rectal hemorrhage ^† 1	2/60 (3.33%)
Rectal pain ^† 1	1/60 (1.67%)
Small intestinal obstruction ^† 1	1/60 (1.67%)
Toothache ^† 1	1/60 (1.67%)
Vomiting ^† 1	12/60 (20.00%)
Gastrointestinal disorders - Other, specify ^† 1	3/60 (5.00%)
General disorders
Chills ^† 1	10/60 (16.67%)
Death NOS ^† 1	1/60 (1.67%)
Edema face ^† 1	1/60 (1.67%)
Edema limbs ^† 1	5/60 (8.33%)
Fatigue ^† 1	34/60 (56.67%)
Fever ^† 1	9/60 (15.00%)
Flu like symptoms ^† 1	1/60 (1.67%)
Hypothermia ^† 1	1/60 (1.67%)
Infusion related reaction ^† 1	8/60 (13.33%)
Irritability ^† 1	1/60 (1.67%)
Malaise ^† 1	6/60 (10.00%)
Non-cardiac chest pain ^† 1	2/60 (3.33%)
Pain ^† 1	5/60 (8.33%)
Sudden death NOS ^† 1	1/60 (1.67%)
General disorders and administration site conditions - Other, specify ^† 1	7/60 (11.67%)
Immune system disorders
Allergic reaction ^† 1	3/60 (5.00%)
Infections and infestations
Abdominal infection ^† 1	1/60 (1.67%)
Anorectal infection ^† 1	2/60 (3.33%)
Bronchial infection ^† 1	1/60 (1.67%)
Eye infection ^† 1	1/60 (1.67%)
Lung infection ^† 1	1/60 (1.67%)
Sepsis ^† 1	2/60 (3.33%)
Sinusitis ^† 1	1/60 (1.67%)
Skin infection ^† 1	1/60 (1.67%)
Tooth infection ^† 1	1/60 (1.67%)
Upper respiratory infection ^† 1	4/60 (6.67%)
Urinary tract infection ^† 1	4/60 (6.67%)
Infections and infestations - Other, specify ^† 1	3/60 (5.00%)
Injury, poisoning and procedural complications
Bruising ^† 1	2/60 (3.33%)
Burn ^† 1	2/60 (3.33%)
Fall ^† 1	2/60 (3.33%)
Investigations
Activated partial thromboplastin time prolonged ^† 1	2/60 (3.33%)
Alanine aminotransferase increased ^† 1	8/60 (13.33%)
Alkaline phosphatase increased ^† 1	10/60 (16.67%)
Aspartate aminotransferase increased ^† 1	12/60 (20.00%)
Blood bilirubin increased ^† 1	6/60 (10.00%)
Creatinine increased ^† 1	3/60 (5.00%)
INR increased ^† 1	3/60 (5.00%)
Lymphocyte count decreased ^† 1	8/60 (13.33%)
Neutrophil count decreased ^† 1	7/60 (11.67%)
Platelet count decreased ^† 1	15/60 (25.00%)
Weight loss ^† 1	10/60 (16.67%)
White blood cell decreased ^† 1	6/60 (10.00%)
Investigations - Other, specify ^† 1	1/60 (1.67%)
Metabolism and nutrition disorders
Alcohol intolerance ^† 1	1/60 (1.67%)
Anorexia ^† 1	16/60 (26.67%)
Dehydration ^† 1	10/60 (16.67%)
Hypercalcemia ^† 1	4/60 (6.67%)
Hyperglycemia ^† 1	24/60 (40.00%)
Hyperkalemia ^† 1	5/60 (8.33%)
Hypermagnesemia ^† 1	1/60 (1.67%)
Hypernatremia ^† 1	4/60 (6.67%)
Hypertriglyceridemia ^† 1	1/60 (1.67%)
Hypoalbuminemia ^† 1	6/60 (10.00%)
Hypocalcemia ^† 1	8/60 (13.33%)
Hypoglycemia ^† 1	6/60 (10.00%)
Hypokalemia ^† 1	8/60 (13.33%)
Hypomagnesemia ^† 1	4/60 (6.67%)
Hyponatremia ^† 1	12/60 (20.00%)
Hypophosphatemia ^† 1	1/60 (1.67%)
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	3/60 (5.00%)
Back pain ^† 1	10/60 (16.67%)
Bone pain ^† 1	1/60 (1.67%)
Buttock pain ^† 1	1/60 (1.67%)
Chest wall pain ^† 1	1/60 (1.67%)
Flank pain ^† 1	1/60 (1.67%)
Generalized muscle weakness ^† 1	4/60 (6.67%)
Muscle weakness lower limb ^† 1	1/60 (1.67%)
Muscle weakness upper limb ^† 1	1/60 (1.67%)
Myalgia ^† 1	7/60 (11.67%)
Neck pain ^† 1	2/60 (3.33%)
Pain in extremity ^† 1	5/60 (8.33%)
Musculoskeletal and connective tissue disorder - Other, specify ^† 1	2/60 (3.33%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain ^† 1	1/60 (1.67%)
Nervous system disorders
Dizziness ^† 1	3/60 (5.00%)
Headache ^† 1	5/60 (8.33%)
Lethargy ^† 1	1/60 (1.67%)
Paresthesia ^† 1	1/60 (1.67%)
Peripheral sensory neuropathy ^† 1	1/60 (1.67%)
Presyncope ^† 1	2/60 (3.33%)
Nervous system disorders - Other, specify ^† 1	2/60 (3.33%)
Psychiatric disorders
Anxiety ^† 1	7/60 (11.67%)
Confusion ^† 1	3/60 (5.00%)
Delirium ^† 1	1/60 (1.67%)
Depression ^† 1	6/60 (10.00%)
Insomnia ^† 1	11/60 (18.33%)
Psychiatric disorders - Other, specify ^† 1	3/60 (5.00%)
Renal and urinary disorders
Acute kidney injury ^† 1	1/60 (1.67%)
Hematuria ^† 1	1/60 (1.67%)
Proteinuria ^† 1	2/60 (3.33%)
Urinary frequency ^† 1	1/60 (1.67%)
Urinary incontinence ^† 1	1/60 (1.67%)
Urinary retention ^† 1	1/60 (1.67%)
Reproductive system and breast disorders
Erectile dysfunction ^† 1	1/60 (1.67%)
Pelvic pain ^† 1	2/60 (3.33%)
Uterine pain ^† 1	1/60 (1.67%)
Vaginal discharge ^† 1	1/60 (1.67%)
Vaginal hemorrhage ^† 1	1/60 (1.67%)
Respiratory, thoracic and mediastinal disorders
Cough ^† 1	5/60 (8.33%)
Dyspnea ^† 1	7/60 (11.67%)
Epistaxis ^† 1	2/60 (3.33%)
Hiccups ^† 1	1/60 (1.67%)
Hypoxia ^† 1	1/60 (1.67%)
Laryngeal edema ^† 1	1/60 (1.67%)
Nasal congestion ^† 1	1/60 (1.67%)
Pleural effusion ^† 1	1/60 (1.67%)
Postnasal drip ^† 1	2/60 (3.33%)
Pulmonary edema ^† 1	2/60 (3.33%)
Sore throat ^† 1	1/60 (1.67%)
Respiratory, thoracic and mediastinal disorders - Other, specify ^† 1	1/60 (1.67%)
Skin and subcutaneous tissue disorders
Alopecia ^† 1	1/60 (1.67%)
Dry skin ^† 1	2/60 (3.33%)
Hyperhidrosis ^† 1	2/60 (3.33%)
Nail ridging ^† 1	1/60 (1.67%)
Palmar-plantar erythrodysesthesia syndrome ^† 1	1/60 (1.67%)
Rash acneiform ^† 1	1/60 (1.67%)
Rash maculo-papular ^† 1	8/60 (13.33%)
Skin hyperpigmentation ^† 1	1/60 (1.67%)
Skin ulceration ^† 1	1/60 (1.67%)
Skin and subcutaneous tissue disorders - Other, specify ^† 1	4/60 (6.67%)
Surgical and medical procedures
Surgical and medical procedures - Other, specify ^† 1	2/60 (3.33%)
Vascular disorders
Flushing ^† 1	5/60 (8.33%)
Hot flashes ^† 1	1/60 (1.67%)
Hypertension ^† 1	6/60 (10.00%)
Hypotension ^† 1	5/60 (8.33%)
Thromboembolic event ^† 1	1/60 (1.67%)
Vascular disorders - Other, specify ^† 1	1/60 (1.67%)
† Indicates events were collected by systematic assessment 1 Term from vocabulary, CTCAE (4.0)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Matthew H. Kulke, MD
Organization:	Dana-Farber Cancer Institute
Phone:	617.632.5136
EMail:	Matthew_Kulke@dfci.harvard.edu

Publications:

Strosberg JR, Chan JA, Ryan DP, Meyerhardt JA, Fuchs CS, Abrams T, Regan E, Brady R, Weber J, Campos T, Kvols LK, Kulke MH. A multi-institutional, phase II open-label study of ganitumab (AMG 479) in advanced carcinoid and pancreatic neuroendocrine tumors. Endocr Relat Cancer. 2013 May 21;20(3):383-90. doi: 10.1530/ERC-12-0390. Print 2013 Jun.

Layout table for additonal information

Responsible Party:	Matthew H. Kulke, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:	NCT01024387
Other Study ID Numbers:	09-240
First Submitted:	December 1, 2009
First Posted:	December 2, 2009
Results First Submitted:	November 30, 2017
Results First Posted:	December 27, 2017
Last Update Posted:	March 8, 2018

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