MDX-010 in Treating Patients With Stage IV Pancreatic Cancer That Cannot Be Removed By Surgery

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00112580
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 27
• Locations: 2
• Actual Duration (Months): 47
• Patients Per Site: 13.5
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

RATIONALE: Biological therapies, such as MDX-010, may stimulate the immune system in different ways and stop tumor cells from growing.

PURPOSE: This phase II trial is studying how well MDX-010 works in treating patients with stage IV pancreatic cancer that cannot be removed by surgery.

Condition or Disease	Intervention/Treatment	Phase
Pancreatic Cancer	Biological: ipilimumab	Phase 2

Detailed Description

OBJECTIVES:

Primary

• Determine clinical response (partial and complete responses) in patients with unresectable stage IV (locally or distantly metastatic) pancreatic adenocarcinoma treated with anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010).

Secondary

• Determine whether observed responses correlate with the incidence of autoimmunity in patients treated with this drug.

OUTLINE: This is an open-label study. Patients are stratified according to status of disease (locally vs distantly metastatic).

Patients receive anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010) IV over 90 minutes on days 0, 21, 42, and 63. Treatment repeats every 84 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients with disease progression after achieving a partial response or complete response receive 2 additional courses of therapy.

After completion of study treatment, patients are followed at 3 weeks, every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 42-82 patients (21-41 per stratum) will be accrued for this study within 2-4 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 27 participants
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Single Agent Ipilimumab (MDX-010 Anti CTLA-4) for Subjects With Locally Advanced or Metastatic Pancreatic Adenocarcinoma
• Actual Study Start Date: Jul 31, 2005
• Actual Primary Completion Date: Jun 30, 2009
• Actual Study Completion Date: Jun 30, 2009

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) [From first dose to 3 weeks following the end of the treatment cycle, up to 24 weeks.]

   Percentage of participants who achieved Complete Response (CR) or Partial Response (PR) according to RECIST criteria. Particularly, CR is defined as disappearance of all target lesions, while PR is defined as at least a 30% decrease n the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Histologically confirmed pancreatic adenocarcinoma

• Stage IV disease

• Locally (invasion of adjacent structures, including mesenteric arteries or organs) or distantly metastatic disease

• Unresectable disease

• Pancreatic adenocarcinoma with intraductal papillary mucinous neoplasm allowed

• The following diagnoses are not allowed:

• Acinar cell carcinoma

• Pancreaticoblastoma

• Malignant cystic neoplasms

• Endocrine neoplasms

• Squamous cell carcinoma

• Vater and periampullary duodenal or common bile duct malignancies

• Clinically evaluable disease with ≥ 1 site of measurable disease

• Biliary or gastric outlet obstruction allowed provided it is effectively drained by endoscopic, operative, or interventional means

• Pancreatic, biliary, or enteric fistulae allowed provided they are controlled with an appropriate drain

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 3 months

Hematopoietic

• WBC ≥ 2,500/mm^3

• Absolute neutrophil count ≥ 1,500/mm^3

• Platelet count ≥ 100,000/mm^3

• Hemoglobin ≥ 9 g/dL

• Hematocrit ≥ 27%

Hepatic

• Hepatitis B surface antigen negative

• Hepatitis C virus antibody negative OR

• Hepatitis C RNA negative by polymerase chain reaction

Renal

• Creatinine < 2.0 mg/dL

Immunologic

• HIV negative

• No history of or active autoimmune disease, including uveitis or autoimmune inflammatory eye disease

• No active uncontrolled infection

Other

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix

• No underlying medical condition that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010)

Chemotherapy

• At least 3 weeks since prior chemotherapy for pancreatic adenocarcinoma and recovered

• No concurrent chemotherapy

Endocrine therapy

• More than 4 weeks since prior corticosteroids

• No concurrent systemic or topical corticosteroids

Radiotherapy

• At least 3 weeks since prior radiotherapy for pancreatic adenocarcinoma and recovered

Surgery

• See Disease Characteristics

Other

• At least 3 weeks since other prior therapy for pancreatic adenocarcinoma and recovered

• No concurrent immunosuppressants (e.g., cyclosporin or its analog)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office	Bethesda	Maryland	United States	20892-1182
2	NCI - Surgery Branch	Bethesda	Maryland	United States	20892

Sponsors and Collaborators

• Bristol-Myers Squibb
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Steven A. Rosenberg, MD, PhD, NCI - Surgery Branch

Study Documents (Full-Text)

• Study Protocol - Mar 24, 2005
• Statistical Analysis Plan - Jan 6, 2009

More Information

Publications

None provided.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT00112580
• Other Study ID Numbers: CDR0000430666; NCI-05-C-0141; NCI-P6557; MDX-010-24; NCT00108888
• First Posted: Jun 3, 2005
• Last Update Posted: Sep 27, 2021
• Last Verified: Sep 1, 2021

• Keywords provided by Bristol-Myers Squibb: recurrent pancreatic cancer; adenocarcinoma of the pancreas; stage IV pancreatic cancer
• Additional relevant MeSH terms: Pancreatic Neoplasms; Ipilimumab

Study Results

Participant Flow

Pre-assignment Detail	27 participants were treated.

Arm/Group Title	Locally Advanced Cohort	Metastatic Cohort
Arm/Group Description	Participants with locally advanced pancreatic adenocarcinoma. Treated with Ipilimumab administered at 3 mg/Kg dose every 3 weeks.	Participants with metastatic pancreatic adenocarcinoma. Treated with Ipilimumab administered at 3 mg/Kg dose every 3 weeks.
Period Title: Overall Study
STARTED	8	19
COMPLETED	0	0
NOT COMPLETED	8	19

Baseline Characteristics

Arm/Group Title	Locally Advanced Cohort	Metastatic Cohort	Total
Arm/Group Description	Participants with locally advanced pancreatic adenocarcinoma. Treated with Ipilimumab administered at 3 mg/Kg dose every 3 weeks.	Participants with metastatic pancreatic adenocarcinoma. Treated with Ipilimumab administered at 3 mg/Kg dose every 3 weeks.	Total of all reporting groups
Overall Participants	8	19	27
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	58.3 (6.48)	51.5 (9.81)	53.5 (9.36)
Sex: Female, Male (Count of Participants)
Female	5 62.5%	7 36.8%	12 44.4%
Male	3 37.5%	12 63.2%	15 55.6%
Race/Ethnicity, Customized (Count of Participants)
White	8 100%	18 94.7%	26 96.3%
Hispanic	0 0%	1 5.3%	1 3.7%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR)
Description	Percentage of participants who achieved Complete Response (CR) or Partial Response (PR) according to RECIST criteria. Particularly, CR is defined as disappearance of all target lesions, while PR is defined as at least a 30% decrease n the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD.
Time Frame	From first dose to 3 weeks following the end of the treatment cycle, up to 24 weeks.

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Locally Advanced Cohort	Metastatic Cohort
Arm/Group Description	Participants with locally advanced pancreatic adenocarcinoma. Treated with Ipilimumab administered at 3 mg/Kg dose every 3 weeks.	Participants with metastatic pancreatic adenocarcinoma. Treated with Ipilimumab administered at 3 mg/Kg dose every 3 weeks.
Measure Participants	8	19
Number [Percent of Participants]	0 0%	0 0%

Adverse Events

Time Frame	All Adverse Events were collected from first dose to study completion (up to approximately 1 year)
Adverse Event Reporting Description	Adverse Events were not monitored/assessed by disease status separately because both cohorts (Locally Advanced cohort and Metastatic cohort) received the same treatment at the same dose. Hence, Adverse Events are reported as a single cohort (Ipilimumab 3 mg/Kg).
Arm/Group Title	Ipilimumab 3 mg/Kg
Arm/Group Description	Participants with locally advanced or metastatic pancreatic adenocarcinoma treated with Ipilimumab administered at 3 mg/Kg dose every 3 weeks.
All Cause Mortality
	Ipilimumab 3 mg/Kg
	Affected / at Risk (%)	# Events
Total	12/27 (44.4%)
Serious Adverse Events
	Ipilimumab 3 mg/Kg
	Affected / at Risk (%)	# Events
Total	20/27 (74.1%)
Blood and lymphatic system disorders
Anaemia	1/27 (3.7%)
Lymphopenia	1/27 (3.7%)
Endocrine disorders
Hypophysitis	1/27 (3.7%)
Gastrointestinal disorders
Abdominal pain	6/27 (22.2%)
Ascites	1/27 (3.7%)
Colitis	1/27 (3.7%)
Diarrhoea	1/27 (3.7%)
Duodenal obstruction	1/27 (3.7%)
Intestinal ischaemia	1/27 (3.7%)
Jejunal ulcer	1/27 (3.7%)
Obstruction gastric	1/27 (3.7%)
Vomiting	1/27 (3.7%)
General disorders
Fatigue	2/27 (7.4%)
Hepatobiliary disorders
Bile duct obstruction	4/27 (14.8%)
Cholangitis	1/27 (3.7%)
Hyperbilirubinaemia	3/27 (11.1%)
Liver disorder	1/27 (3.7%)
Infections and infestations
Infection	2/27 (7.4%)
Sepsis	1/27 (3.7%)
Sinusitis	1/27 (3.7%)
Urinary tract infection	1/27 (3.7%)
Injury, poisoning and procedural complications
Post procedural bile leak	1/27 (3.7%)
Investigations
Alanine aminotransferase increased	1/27 (3.7%)
Aspartate aminotransferase increased	1/27 (3.7%)
Blood alkaline phosphatase increased	2/27 (7.4%)
Blood amylase increased	1/27 (3.7%)
Blood bilirubin increased	1/27 (3.7%)
Lipase increased	1/27 (3.7%)
Metabolism and nutrition disorders
Dehydration	1/27 (3.7%)
Hypoalbuminaemia	1/27 (3.7%)
Hypokalaemia	1/27 (3.7%)
Nervous system disorders
Cerebral ischaemia	1/27 (3.7%)
Embolic cerebral infarction	1/27 (3.7%)
Psychiatric disorders
Confusional state	1/27 (3.7%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/27 (3.7%)
Pulmonary embolism	1/27 (3.7%)
Vascular disorders
Deep vein thrombosis	3/27 (11.1%)
Other (Not Including Serious) Adverse Events
	Ipilimumab 3 mg/Kg
	Affected / at Risk (%)	# Events
Total	26/27 (96.3%)
Blood and lymphatic system disorders
Lymphopenia	2/27 (7.4%)
Gastrointestinal disorders
Abdominal distension	4/27 (14.8%)
Abdominal pain	6/27 (22.2%)
Ascites	4/27 (14.8%)
Constipation	8/27 (29.6%)
Diarrhoea	4/27 (14.8%)
Flatulence	4/27 (14.8%)
Melaena	2/27 (7.4%)
Nausea	9/27 (33.3%)
Vomiting	4/27 (14.8%)
General disorders
Chills	4/27 (14.8%)
Fatigue	13/27 (48.1%)
Oedema	2/27 (7.4%)
Oedema peripheral	5/27 (18.5%)
Pyrexia	11/27 (40.7%)
Hepatobiliary disorders
Hyperbilirubinaemia	5/27 (18.5%)
Infections and infestations
Oral candidiasis	2/27 (7.4%)
Investigations
Alanine aminotransferase increased	4/27 (14.8%)
Aspartate aminotransferase increased	4/27 (14.8%)
Blood alkaline phosphatase increased	6/27 (22.2%)
Haemoglobin decreased	3/27 (11.1%)
Weight decreased	14/27 (51.9%)
Weight increased	2/27 (7.4%)
Metabolism and nutrition disorders
Anorexia	5/27 (18.5%)
Dehydration	2/27 (7.4%)
Hypoalbuminaemia	2/27 (7.4%)
Hypokalaemia	3/27 (11.1%)
Hypomagnesaemia	2/27 (7.4%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/27 (7.4%)
Back pain	6/27 (22.2%)
Nervous system disorders
Headache	2/27 (7.4%)
Psychiatric disorders
Confusional state	2/27 (7.4%)
Insomnia	2/27 (7.4%)
Respiratory, thoracic and mediastinal disorders
Cough	4/27 (14.8%)
Dyspnoea	6/27 (22.2%)
Skin and subcutaneous tissue disorders
Pruritus	3/27 (11.1%)
Rash	6/27 (22.2%)
Vascular disorders
Hypertension	2/27 (7.4%)
Hypotension	4/27 (14.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.