A Study On An Immunostimulant Antibody In Combination With Chemotherapy For Advanced Cancer Of The Pancreas

Pancreatic Neoplasm Clinical Trial

Official title:

A Phase 1 Dose Escalation Open Label Study Of CP-870,893 In Combination With Gemcitabine In Patients With Chemotherapy-Naïve Surgically Incurable Pancreatic Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00711191
• Other study ID #: A5021005
• Status: Completed
• Phase: Phase 1
• First received: June 26, 2008
• Last updated: November 26, 2013
• Start date: June 2008
• Est. completion date: January 2011

Study information

• Verified date: November 2013
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This study aims to seek evidence that activation of certain cells of the immune system will be safe and well tolerated in combination with cytotoxic chemotherapy. Preliminary evidence of clinical anti-tumor activity will be sought.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: January 2011
• Est. primary completion date: January 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 1st-line surgically incurable cancer of the pancreas

• ECOG(Eastern Cooperative Oncology Group) performance status 0-1

Exclusion Criteria:

• Previous systemic therapy for pancreas cancer

• History of cancer-associated blood clots

• History of autoimmune disease

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Pancreatic Neoplasm
• Pancreatic Neoplasms

Intervention

Biological:
• monoclonal antibody
CP-870,893 intravenous administration [IV] on day 3 of 4-week cycles

Drug:
• chemotherapy
gemcitabine 1000 mg/m^2 intravenous administration [IV] q week [wk]x3 of 4-week cycles

Locations

Country	Name	City	State
United States	Pfizer Investigational Site	Indianapolis	Indiana
United States	Pfizer Investigational Site	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Hoffmann-La Roche	University of Pennsylvania

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Recommended Phase 2 Dose (RP2D) of CP-870893 in Participants With Advanced Pancreas Cancer	Additional participants enrolled at MTD of CP-870893 to further characterize suitability for phase 2 testing. RP2D confirmed if = 3 our of 12 participants in expansion cohort experience DLT in cycle 1.	Baseline up to time of determination of maximum tolerated dose (MTD)	Yes
Primary	Number of Participants With Dose Limiting Toxicities (DLTs)	Any of the following during first cycle of treatment and attributable to CP-870893: afebrile Grade (Gr) 4 neutropenia (absolute neutrophil count [ANC] <500 cells/mm^3) =7 days or Gr 3 or 4 neutropenia associated with fever (1 oral temperature >38.5 degrees Celsius (C) or 3 oral temperatures >38.0 degrees C in a 24-hour period); Gr 4 thrombocytopenia or Gr 3 thrombocytopenia associated with bleeding; Gr 4 lymphopenia, if coupled with clinical consequence (such as, opportunistic infection) or any other Gr 3 hematological adverse events; =Gr 3 non-hematologic toxicities (except alopecia).	Baseline up to Cycle 1 / Day 28	Yes
Secondary	Percentage of Participants With Objective Tumor Response According to Response Evaluation Criteria in Solid Tumors (RECIST)	Number of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST. Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as =30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat imaging study =4 weeks after initial documentation of response.	At the end of every even-numbered cycle (cycle=28 days) up to a maximum of 12 cycles and 4 to 6 weeks following initial documentation of response	No
Secondary	Overall Survival (OS)	OS is time from baseline to death from any cause. Participants last known to be alive were censored at the date of last contact.	Baseline, assessed monthly until death or 7.5 months after last participant was enrolled (up to January 2011)	Yes
Secondary	Progression Free Survival (PFS)	PFS is time from baseline to first progression (Prog) or death from any cause. Participants last known to be alive, had not started a new (non-protocol) cancer treatment, were Prog-free, and who had a baseline and =1 on-study disease assessment were censored at date of last objective disease assessment that verified lack of Prog. Participants who were off treatment prior to Prog and who had no on-study disease assessment were also censored. Prog: =20% increase in sum of longest dimension (LD) of target lesions from smallest sum LD recorded since treatment start or appearance of =1 new lesions.	Baseline, assessed monthly until death or 7.5 months after last participant was enrolled (up to January 2011)	No
Secondary	Time to Progression	Disease progression defined as =20% increase in sum LD of target lesions from smallest sum LD recorded since treatment start or appearance of =1 new lesions. Criteria for progression also included unequivocal progression of existing nontarget lesions.	Monthly until death or 7.5 months after last participant was enrolled (up to January 2011)	No
Secondary	Maximum Serum Concentration (Cmax)		Cycle 1 / Day 3 pre-dose, 5 minutes after End of Infusion (EOI), and 2, 6, and 24 hours after EOI and pre-dose on Day 3 of every subsequent cycle up to a maximum of 12 cycles	No
Secondary	Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)	Area under the serum concentration time-curve from time zero to the last measured concentration. AUClast analyzed using a noncompartmental approach to estimate individual participant values.	Cycle 1 / Day 3 pre-dose, 5 minutes after EOI, and 2, 6, and 24 hours after EOI and pre-dose on Day 3 of every subsequent cycle up to a maximum of 12 cycles	No
Secondary	Change (Pre-dose to Post-dose) in Plasma Cytokine Concentrations: Pre-dose Concentration (CYTO0), Maximum Concentration (CTYOMAX)	An increase in values indicates greater cytokine release from cells targeted by the antibody and may be associated with an infusion reaction. Change calculated as mean of pre-dose and maximum post-dose values.	Cycle 1 / Day 1 prior to gemcitabine infusion (0 hour), 5 minutes after EOI and 2, 4, 6, and 24 hours after EOI; Cycle 1 / Day 3 prior to CP-970893 infusion (0 hour), 5 minutes after EOI, and 2, 4, 6, and 24 hours after EOI	No
Secondary	Change (Pre-dose to Post-dose) in Plasma Cytokine Concentrations: Time of Maximum Concentration (TCYTOMAX)	An increase in values indicates greater cytokine release from cells targeted by the antibody and may be associated with an infusion reaction. Change calculated as mean of pre-dose and maximum post-dose values.	Cycle 1 / Day 1 prior to gemcitabine infusion (0 hour), 5 minutes after EOI and 2, 4, 6, and 24 hours after EOI; Cycle 1 / Day 3 prior to CP-970893 infusion (0 hour), 5 minutes after EOI, and 2, 4, 6, and 24 hours after EOI	No
Secondary	Total and Neutralizing Human Antihuman Antibody (HAHA) Titer	HAHA assessed as an indicator of immunogenicity to CP-870893.	Prior to infusion of CP-870893 on Day 3 of every cycle up to a maximum of 12 cycles	Yes
Secondary	Change (Pre-dose to Post-dose) in Bone Marrow Derived Cells (B Cell) Surface Markers: CD54, CD23, CD40, CD86, and Human Leukocyte Antigen (HLA-DR)	Assess the ability of PF-870893 to activate B-cells and HLA-DR which are involved in the production of antibodies. Change calculated as mean of pre-dose and post-dose values. Positive values indicate greater presence of cells associated with antibody production.	Cycle 1 / Day 1 and Cycle 1 / Day 8 prior to gemcitabine infusion and 6 and 24 hours after EOI; Cycle 1 / Day 3 prior to CP-870893 infusion and 6, 24, and 48 hours after EOI	No
Secondary	18-fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) Imaging (MTD Expansion Cohort)	FDG PET assessment to characterize and monitor tumors before and after study treatment; measured as a standardized uptake value (SUV). A reduction in SUV from baseline for at least 1 tumor may indicate a positive metabolic response to treatment.	Baseline, Week 2, Week 8, and Single Time Point (STP) PET for all PET scans after Week 8	No
Secondary	Carbohydrate Antigen 19-9 (CA 19-9)	CA 19-9 or sialylated Lewis (a) antigen (a tumor marker). Values higher than 37 units per milliliter (U/ml) considered abnormal; higher values usually indicate greater presence of disease.	At the end of every even-numbered cycle (cycle=28 days) and 4 to 6 weeks following initial documentation of response	No

External Links

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