A Study Comparing CO-1.01 With Gemcitabine as First Line Therapy in Patients With Metastatic Pancreatic Adenocarcinoma (LEAP)

• Sponsor: Clovis Oncology, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01124786
• Collaborator: (none)
• Enrollment: 367
• Locations: 95
• Arms: 2
• Duration (Months): 37
• Patients Per Site: 3.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether CO-1.01 is safe and effective in the treatment of patients with metastatic pancreatic cancer and low hENT1 expression compared with gemcitabine.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Pancreatic Adenocarcinoma	Drug: CO-1.01; Drug: Gemcitabine	Phase 2

Detailed Description

Pancreatic cancer is a very serious form of cancer. The majority of patients present with unresectable disease, and the condition is often not diagnosed until the cancer is relatively advanced. The standard first-line treatment for patients with unresectable pancreatic cancer is gemcitabine monotherapy. Unfortunately many of these patients fail to derive benefit from this treatment. No clinical or molecular marker has been established to predict benefit from gemcitabine therapy, so patients are treated empirically until evidence of disease progression or worsening performance status.

The potential for human equilibrative nucleoside transporter-1 (hENT1) expression to predict survival in gemcitabine-treated patients has been studied, and data suggest that patients with low levels of tumor cell hENT1 expression derive less benefit from gemcitabine treatment than patients with high levels of tumor cell hENT1 expression. These data support the hypothesis to be tested in this study that patients with pancreatic tumors expressing low levels of hENT1 will derive minimal benefit from gemcitabine, but will receive benefit from CO-1.01 (gemcitabine elaidate) which enters tumor cells in a hENT1-independent fashion.

Study Design

• Study Type: Interventional
• Actual Enrollment: 367 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Randomized, Open-Label, Multicenter Study Comparing CO-1.01 With Gemcitabine as First-Line Therapy in Patients With Metastatic Pancreatic Adenocarcinoma
• Study Start Date: May 1, 2010
• Actual Primary Completion Date: Nov 1, 2012
• Actual Study Completion Date: Jun 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CO-1.01	Drug: CO-1.01; 1250 mg/m2 intravenous infusion weekly for 3 weeks every 4 weeks
Active Comparator: gemcitabine	Drug: Gemcitabine; 1000 mg/m2 intravenous infusion weekly for 7 weeks followed by 1 week rest, then weekly for 3 weeks every 4 weeks

Outcome Measures

Primary Outcome Measures

1. Overall Survival in Patients With Low High Human Equilibrative Nucleoside Transporter 1 (hENT1) Expression [Monthly follow up after treatment discontinuation until death, up to 1.5 years.]

Secondary Outcome Measures

1. Overall Survival in All Patients and Patients With hENT1 Expression [Monthly follow up after treatment discontinuation until death, up to 1.5 years]

2. ORR, Duration of Response, and Progression Free Survival (PFS) in Patients With Measurable/Evaluable Disease, Using RECIST 1.1, up to 1.5 Years [Every 8 weeks]

3. Cancer Antigen (CA)19-9 Response Rates [Every 4 weeks, up to 1.5 years]

4. Drug Tolerability and Toxicity [Every week, up to 1.5 years]

5. Change From Baseline in Pain Severity [Every 4 weeks, up to 1.5 years]

6. Change From Baseline in Health Status [Every 4 weeks, up to 1.5 years]

7. Pharmacokinetic (PK) Profile of CO-1.01 Based on Sparse Sampling [30 days after first dose]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Metastatic pancreatic ductal adenocarcinoma (i.e., Stage 4).

• Histological/cytological confirmation of metastatic tissue (not primary tumor) by a central pathology laboratory (H&E stain) to ensure sufficient material is available for later hENT1 analysis.

• Adjuvant chemotherapy/radiotherapy ≥ 6 months prior to randomization.

• Palliative radiotherapy (if administered) ≥ 1 month prior to randomization.

• CT scan ≤30 days prior to randomization

• Performance Status (ECOG) 0 or 1.

• Estimated life expectancy ≥ 12 weeks.

• Age ≥ 18 years.

• Adequate hematological and biological function.

• Written consent on an Institutional Review Board/Institutional Ethics Committee-approved Informed Consent Form prior to any study-specific evaluation.

Exclusion Criteria:

• Prior palliative chemotherapy for pancreatic cancer.

• Radical pancreatic resections (e.g., Whipple procedure) are not allowed < 6 months prior to randomization. Exploratory laparotomy, palliative (e.g., bypass) surgery, or other procedures (e.g., stents) are not allowed < 14 days prior to randomization. In both cases the patient must be sufficiently recovered and stable.

• Symptomatic brain metastases.

• Participation in other investigational drug clinical studies ≤ 30 days prior to randomization.

• Concomitant treatment with prohibited medications.

• History of allergy to gemcitabine or eggs.

• Presence of any serious or unstable concomitant systemic disorder incompatible with the clinical study (e.g., substance abuse, uncontrolled intercurrent illness including active infection, arterial thrombosis, symptomatic pulmonary embolism).

• Any disorder that would hamper protocol compliance.

• Prior nonpancreatic malignancy treated with chemotherapy. Prior malignancies treated with surgery or radiotherapy alone must be in remission ≥ 3 years. The following prior malignancies are allowable irrespective of when they occurred: in situ carcinoma of the cervix, in situ ductal breast cancer, low-grade local bladder cancer, and nonmelanotic skin cancer.

• Females who are pregnant or breastfeeding.

• Refusal to use adequate contraception for fertile patients (females and males during the study and for 6 months after the last study treatment). Adequate forms of contraception are double-barrier methods (condoms or diaphragm with spermicidal jelly or foam); oral, depot, or injectable contraceptives; intrauterine devices; tubal ligation.

• Any other reason the investigator considers the patient should not participate in the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Center for Hematology Oncology	Glendale	Arizona	United States	85306
2	Wilshire Oncology Medical Group, Inc.	Corona	California	United States	92879
3	White Memorial Medical Center	Los Angeles	California	United States	90033
4	Cancer Care Institute	Los Angeles	California	United States	90036
5	Newport Cancer Care Medical	Newport Beach	California	United States	92660
6	Hematology Oncology Associates	Oakland	California	United States	94609
7	Sharp Clinical Oncology Research	San Diego	California	United States	92123
8	Rocky Mountain Cancer Centers	Denver	Colorado	United States	80218
9	Hartford Hospital Clinical Research	Hartford	Connecticut	United States	06102
10	Oncology Associates of Bridgeport	Trumbull	Connecticut	United States	06611
11	Annapolis Oncology Center	Annapolis	Maryland	United States	21401
12	Virginia Piper Cancer Institute	Minneapolis	Minnesota	United States	55407
13	The Cancer Institute of New Jersey	New Brunswick	New Jersey	United States	08901
14	New Mexico Cancer Care Alliance	Albuquerque	New Mexico	United States	87109
15	Arena Oncology Associates, PC	Lake Success	New York	United States	11042
16	Bend Memorial Clinic	Bend	Oregon	United States	97701
17	Cancer Center of the Carolinas	Greenville	South Carolina	United States	29605
18	Cancer Specialists of South Texas, P.A.	Corpus Christi	Texas	United States	78412
19	Valley Cancer Associates	Harlingen	Texas	United States	78550
20	South Texas Oncology and Hematology, PA	San Antonio	Texas	United States	78229
21	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
22	Policlínica Privada Instituto de Medicina Nuclear	Buenos Aires	Bahia Blanca	Argentina	B8000FJI
23	Instituto Especializado Alexander Fleming	Cuidad Autónoma de Buenos Aires	Buenos Aires	Argentina	C1426ANZ
24	Hospital de Gastroenterología	Loma Hermosa	Buenos Aires	Argentina	B1657BHD
25	Clínica Universitaria Reina Fabiola	Córdoba		Argentina	X5004FHP
26	ISIS Centro Especializado	Santa Fe		Argentina	S3000FFU
27	Newcastle Private Hospital	New Lambton Heights	New South Wales	Australia	2305
28	Port Macquarie Base Hospital	Port Macquarie	New South Wales	Australia	2444
29	Southern Medical Day Oncology Care Centre	Wollongong	New South Wales	Australia	2500
30	Flinders Medical Centre	Bedford Park	South Australia	Australia	5042
31	Saint Vincent's Hospital	Fitzroy	Victoria	Australia	3065
32	Border Medical Oncology, Murray Valley Private Hospital	Wodonga	Victoria	Australia	3690
33	Universitair Ziekenhuis Antwerpen	Edegem	Antwerpen	Belgium	2650
34	Cliniques Universitaires Saint Luc	Brussels		Belgium	1200
35	Centre Hospitalier de Jolimont-Lobbes	Haine-Saint-Paul		Belgium	7100
36	Hospital Universitario	Brasilia	Distrito Federal	Brazil	70840
37	Santa Casa de Misericordia de Belo Horizonte	Belo Horizonte	Minas Gerais	Brazil	60430-230
38	Irmandade da Santa	Porto Alegre	Rio Grande do Sul	Brazil	90020
39	Hospital São Lucas - PUCRS	Porto Alegre	Rio Grande Do Sul	Brazil	90610-000
40	CEPON-Centro de pesquisas Oncologicas	Florianópolis	Santa Catarina	Brazil	88034-000
41	Hospital do Cancer de Barretos	Barretos	Sao Paulo	Brazil	14784-400
42	Fundacao Hospital	Jau	Sao Paulo	Brazil	17210
43	Faculdade de Medicina do ABC	Santo Andre	Sao Paulo	Brazil	09060-650
44	Instituto Nacional do Cancer	Rio de Janeiro		Brazil	20231
45	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
46	Centre Hospitalier de la Cote Basque	Bayonne Cedex		France	64109
47	Hôpital Saint André, Service d'Oncologie Médicale	Bordeaux		France	33000
48	Clinique François Chénieux	Limoges Cedex		France	87039
49	Centre Hospitalier Régional Universitaire Hôpital Saint Eloi	Montpellier Cedex 5		France	34295
50	Centre Regional de Lutte contre le Cancer Val d'Aurelle	Montpellier		France	34298
51	Centre René Gauducheau	Saint Herblain cedex		France	44805
52	Institut Gustave-Roussy - Centre de Lutte Contre le Cancer	Villejuif Cedex		France	94805
53	Ludwig-Maximilians-Universität, Medizinische Klinik und Poliklinikversität München	München	Bayern	Germany	81377
54	Klinikum der Ernst-Moritz-Arndt-Universität	Greifswald	Mecklenburg-Vorpommern	Germany	17475
55	Knappschaftskrankenhaus Bochum-Langendreer	Bochum	Nordrhein-Westfalen	Germany	44892
56	Universitätsklinikum Jena	Jena	Thueringen	Germany	07740
57	Charité Universitätsmedizin Berlin	Berlin		Germany	13353
58	Universitätsklinikum Carl Gustav Carus	Dresden		Germany	01307
59	Klinik der Otto-Von-Guericke-Universität Magdeburg	Magdeburg		Germany	39120
60	Medizinische Universitätsklinik Ulm, Abt. Innere Medizin I	Ulm		Germany	89081
61	Azienda Ospedaliero-Universitaria di Bologna - Policlinico S.Orsola-Malpighi	Bologna	Emilia-Romagna	Italy	40138
62	Fondazione San Raffaele del Monte Tabor	Milano		Italy	20132
63	Instituto Oncologico Veneto, Oncologia Medica 1	Padova		Italy	35128
64	Ospedali Riuniti di Ancona	Torrette di Ancona		Italy	60020
65	Centro Ricerche Cliniche di Verona	Verona		Italy	37134
66	Vrije Universiteit Medisch Centrum	Amsterdam	Noord-Holland	Netherlands	1081 HV
67	Sørlandet sykehus HF	Kristiansand		Norway	4604
68	Oslo Universitetssykehus, Ullevål	Oslo		Norway	0407
69	Republic Clinical Oncology Center	Izhevsk	Republic of Udmurtia	Russian Federation	426067
70	Sverdlovsk Regional Oncology Center	Ekaterinburg		Russian Federation	620036
71	Regional Oncology Center	Irkutsk		Russian Federation	664035
72	Clinical Oncology Center #1	Krasnodar		Russian Federation	350040
73	Kursk Regional Oncology Center	Kursk		Russian Federation	305035
74	Blokhin Cancer Research Center	Moscow		Russian Federation	115478
75	Novosibirsk, City Clinical Hospital #1	Novosibirsk		Russian Federation	630047
76	Leningrad Regional Clinical Hospital	St. Petersburg		Russian Federation	194291
77	Mechnikov St. Petersburg State Medical Academy	St. Petersburg		Russian Federation	195067
78	St. Petersburg City Oncology Center	St. Petersburg		Russian Federation	197785
79	Tambov Regional Oncology Center	Tambov		Russian Federation	392013
80	Tula Regional Oncology Center	Tula		Russian Federation	300053
81	Regional Clinical Oncology Hospital	Yaroslavl		Russian Federation	150040
82	Lanssjukhuset Ryhov	Jonkoping		Sweden	551 85
83	Linköping University Hospital	Linköping		Sweden	581 85
84	Växjö Centrallasarettet	Växjö		Sweden	351 85
85	Dnipropetrovsk City Multispecialty Clinical Hospital #4, Department of Chemotherapy, Dnipropetrovsk State Medical Academy, Department of Oncology and Medical Radiology	Dnipropetrovsk		Ukraine	49102
86	Public Clinical Treatment and Prophylaxis Institution "Donetsk Regional Antitumor Center", Oncosurgery Department #6	Donetsk		Ukraine	83092
87	"Public Healthcare Institution ""Kharkiv Regional Clinical Oncology Center"", Abdominal Department	Kharkiv		Ukraine	61070
88	National Cancer Institute, Department of Tumors of Abdominal Cavity and Retroperitoneum	Kiev		Ukraine	03022
89	State Regional Diagnostics and Treatment Oncology Center, Chemotherapy Department	Lviv		Ukraine	79031
90	Mykolayiv Regional Oncology Center, Surgery Department #1	Mykolayiv		Ukraine	54044
91	Zakarpatya Regional Clinical Oncology Center, Chemotherapy Department	Uzhorod		Ukraine	88014
92	Clinical Facility: Public Institution "Zaporizhya City Clinical Hospital #3", Regional Center of Hepatic, Biliary Tract and Pancreatic Surgery, Surgery Department #1	Zaporizhya		Ukraine	69032
93	Hammersmith Hospital	London	England	United Kingdom	W12 0HS
94	Christie Hospital	Manchester	England	United Kingdom	M20 4BX
95	Beatson West of Scotland Cancer Centre, Cancer Research UK Clinical Trials Unit (CTU)	Glasgow	Scotland	United Kingdom	G12 0YN

Sponsors and Collaborators

• Clovis Oncology, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Clovis Oncology, Inc.
• ClinicalTrials.gov Identifier: NCT01124786
• Other Study ID Numbers: CO-101-001
• First Posted: May 17, 2010
• Last Update Posted: Apr 17, 2014
• Last Verified: Mar 1, 2014

• Keywords provided by Clovis Oncology, Inc.: cancer; metastatic; pancreatic; pancreas; adenocarcinoma; gemcitabine; human equilibrative nucleoside transporter-1 (hENT1); CO-1.01; CO-101; CO101; Stage 4; Stage IV
• Additional relevant MeSH terms: Adenocarcinoma; Gemcitabine

Study Results

Participant Flow

Recruitment Details	This was a multicenter, multinational study conducted at 98 medical centers in Europe, Australia, and the Americas. The first patient was randomized on 04-Aug-2010 and the last patient on 09-April-2012.
Pre-assignment Detail	Eligible patients were randomized (1:1) to receive either gemcitabine elaidate or gemcitabine. The stratification factors in this model were Eastern Cooperative Group Performance Status (ECOG PS) (0 vs 1) and region (North America/Western Europe/Australia vs Eastern Europe vs South America).

Arm/Group Title	CO-1.01	Gemcitabine
Arm/Group Description	CO-1.01 : 1250 mg/m2 intravenous infusion weekly for 3 weeks every 4 weeks	Gemcitabine : 1000 mg/m2 intravenous infusion weekly for 7 weeks followed by 1 week rest, then weekly for 3 weeks every 4 weeks
Period Title: Overall Study
STARTED	182	185
Intent-to-Treat (ITT) Population	182	185
Safety Population	179	181
Tumor Evaluable Population	178	180
COMPLETED	178	180
NOT COMPLETED	4	5

Baseline Characteristics

Arm/Group Title	Gemcitabine Elaidate	Gemcitabine	Total
Arm/Group Description	CO-1.01 : 1250 mg/m2 intravenous infusion weekly for 3 weeks every 4 weeks	Gemcitabine : 1000 mg/m2 intravenous infusion weekly for 7 weeks followed by 1 week rest, then weekly for 3 weeks every 4 weeks	Total of all reporting groups
Overall Participants	182	185	367
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	103 56.6%	116 62.7%	219 59.7%
>=65 years	79 43.4%	69 37.3%	148 40.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.5 (9.62)	60.5 (11.19)	61.5 (10.47)
Sex: Female, Male (Count of Participants)
Female	74 40.7%	74 40%	148 40.3%
Male	108 59.3%	111 60%	219 59.7%
Region of Enrollment (participants) [Number]
United States	18 9.9%	22 11.9%	40 10.9%
Ukraine	40 22%	47 25.4%	87 23.7%
Russian Federation	45 24.7%	40 21.6%	85 23.2%
Italy	8 4.4%	9 4.9%	17 4.6%
United Kingdom	11 6%	10 5.4%	21 5.7%
France	19 10.4%	10 5.4%	29 7.9%
Canada	5 2.7%	2 1.1%	7 1.9%
Argentina	2 1.1%	6 3.2%	8 2.2%
Brazil	7 3.8%	3 1.6%	10 2.7%
Belgium	6 3.3%	4 2.2%	10 2.7%
Australia	4 2.2%	5 2.7%	9 2.5%
Germany	14 7.7%	17 9.2%	31 8.4%
Norway	2 1.1%	3 1.6%	5 1.4%
Sweden	1 0.5%	7 3.8%	8 2.2%

Outcome Measures

1. Primary Outcome

Title	Overall Survival in Patients With Low High Human Equilibrative Nucleoside Transporter 1 (hENT1) Expression
Time Frame	Monthly follow up after treatment discontinuation until death, up to 1.5 years.

Outcome Measure Data

Analysis Population Description

Analysis was per protocol and included hENT-1 low Intent to Treat (IIT) population.

Arm/Group Title	CO-1.01	Gemcitabine
Arm/Group Description	CO-1.01 : 1250 mg/m2 intravenous infusion weekly for 3 weeks every 4 weeks	Gemcitabine : 1000 mg/m2 intravenous infusion weekly for 7 weeks followed by 1 week rest, then weekly for 3 weeks every 4 weeks
Measure Participants	114	118
Median (95% Confidence Interval) [months]	5.7	6.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CO-1.01, Gemcitabine
	Comments	If the median Overall Survival (OS) for the CO-1.01-treated patients is 7.7 months and the median OS for gemcitabine-treated patients with hENT1-low status is 4 months (hazard ratio of 0.53), then a total of 144 events of death in the hENT1-low subgroup will provide over 90% power at a 0.05 (2 sided) significance level for the comparison of CO-1.01 to gemcitabine in the hENT1-low patients.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.973
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.994
	Confidence Interval	(2-Sided) 95%; 0.746 to 1.326
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio and confidence interval presented above, so parameter dispersion not indicated in standard deviation field directly above.

2. Secondary Outcome

Title	Overall Survival in All Patients and Patients With hENT1 Expression
Time Frame	Monthly follow up after treatment discontinuation until death, up to 1.5 years

Outcome Measure Data

Analysis Population Description

Due to Primary endpoint showing lack of efficacy, development of CO-1.01 was stopped and secondary endpoints were not analyzed.

Arm/Group Title	CO-1.01	Gemcitabine
Arm/Group Description	CO-1.01 : 1250 mg/m2 intravenous infusion weekly for 3 weeks every 4 weeks	Gemcitabine : 1000 mg/m2 intravenous infusion weekly for 7 weeks followed by 1 week rest, then weekly for 3 weeks every 4 weeks
Measure Participants	0	0

3. Secondary Outcome

Title	ORR, Duration of Response, and Progression Free Survival (PFS) in Patients With Measurable/Evaluable Disease, Using RECIST 1.1, up to 1.5 Years
Time Frame	Every 8 weeks

Outcome Measure Data

Analysis Population Description

Due to Primary endpoint showing lack of efficacy, development of CO-1.01 was stopped and secondary endpoints were not analyzed.

Arm/Group Title	CO-1.01	Gemcitabine
Arm/Group Description	CO-1.01 : 1250 mg/m2 intravenous infusion weekly for 3 weeks every 4 weeks	Gemcitabine : 1000 mg/m2 intravenous infusion weekly for 7 weeks followed by 1 week rest, then weekly for 3 weeks every 4 weeks
Measure Participants	0	0

4. Secondary Outcome

Title	Cancer Antigen (CA)19-9 Response Rates
Time Frame	Every 4 weeks, up to 1.5 years

Outcome Measure Data

Analysis Population Description

Due to Primary endpoint showing lack of efficacy, development of CO-1.01 was stopped and secondary endpoints were not analyzed.

Arm/Group Title	CO-1.01	Gemcitabine
Arm/Group Description	CO-1.01 : 1250 mg/m2 intravenous infusion weekly for 3 weeks every 4 weeks	Gemcitabine : 1000 mg/m2 intravenous infusion weekly for 7 weeks followed by 1 week rest, then weekly for 3 weeks every 4 weeks
Measure Participants	0	0

5. Secondary Outcome

Title	Drug Tolerability and Toxicity
Time Frame	Every week, up to 1.5 years

Outcome Measure Data

Analysis Population Description

Due to Primary endpoint showing lack of efficacy, development of CO-1.01 was stopped and secondary endpoints were not analyzed.

Arm/Group Title	CO-1.01	Gemcitabine
Arm/Group Description	CO-1.01 : 1250 mg/m2 intravenous infusion weekly for 3 weeks every 4 weeks	Gemcitabine : 1000 mg/m2 intravenous infusion weekly for 7 weeks followed by 1 week rest, then weekly for 3 weeks every 4 weeks
Measure Participants	0	0

6. Secondary Outcome

Title	Change From Baseline in Pain Severity
Time Frame	Every 4 weeks, up to 1.5 years

Outcome Measure Data

Analysis Population Description

Due to Primary endpoint showing lack of efficacy, development of CO-1.01 was stopped and secondary endpoints were not analyzed.

Arm/Group Title	CO-1.01	Gemcitabine
Arm/Group Description	CO-1.01 : 1250 mg/m2 intravenous infusion weekly for 3 weeks every 4 weeks	Gemcitabine : 1000 mg/m2 intravenous infusion weekly for 7 weeks followed by 1 week rest, then weekly for 3 weeks every 4 weeks
Measure Participants	0	0

7. Secondary Outcome

Title	Change From Baseline in Health Status
Time Frame	Every 4 weeks, up to 1.5 years

Outcome Measure Data

Analysis Population Description

Due to Primary endpoint showing lack of efficacy, development of CO-1.01 was stopped and secondary endpoints were not analyzed.

Arm/Group Title	CO-1.01	Gemcitabine
Arm/Group Description	CO-1.01 : 1250 mg/m2 intravenous infusion weekly for 3 weeks every 4 weeks	Gemcitabine : 1000 mg/m2 intravenous infusion weekly for 7 weeks followed by 1 week rest, then weekly for 3 weeks every 4 weeks
Measure Participants	0	0

8. Secondary Outcome

Title	Pharmacokinetic (PK) Profile of CO-1.01 Based on Sparse Sampling
Time Frame	30 days after first dose

Outcome Measure Data

Analysis Population Description

Due to Primary endpoint showing lack of efficacy, development of CO-1.01 was stopped and secondary endpoints were not analyzed.

Arm/Group Title	CO-1.01	Gemcitabine
Arm/Group Description	CO-1.01 : 1250 mg/m2 intravenous infusion weekly for 3 weeks every 4 weeks	Gemcitabine : 1000 mg/m2 intravenous infusion weekly for 7 weeks followed by 1 week rest, then weekly for 3 weeks every 4 weeks
Measure Participants	0	0

Adverse Events

Time Frame	Adverse events were assessed from the time of informed consent to 28 days after the last study drug administration, up to 1.5 years.
Arm/Group Title	CO-1.01		Gemcitabine
Arm/Group Description	CO-1.01 : 1250 mg/m2 intravenous infusion weekly for 3 weeks every 4 weeks		Gemcitabine : 1000 mg/m2 intravenous infusion weekly for 7 weeks followed by 1 week rest, then weekly for 3 weeks every 4 weeks
All Cause Mortality
	CO-1.01		Gemcitabine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	CO-1.01		Gemcitabine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	82/179 (45.8%)		82/181 (45.3%)
Blood and lymphatic system disorders
Anaemia	6/179 (3.4%)		3/181 (1.7%)
Leukopenia	1/179 (0.6%)		0/181 (0%)
Thrombocytopenia	2/179 (1.1%)		0/181 (0%)
Cardiac disorders
Acute myocardial infarction	2/179 (1.1%)		0/181 (0%)
Atrial fibrillation	0/179 (0%)		2/181 (1.1%)
Cardiac failure	1/179 (0.6%)		2/181 (1.1%)
Cardiac failure acute	1/179 (0.6%)		0/181 (0%)
Cardiovascular disorder	1/179 (0.6%)		0/181 (0%)
Gastrointestinal disorders
Abdominal pain	3/179 (1.7%)		2/181 (1.1%)
Abdominal pain upper	1/179 (0.6%)		0/181 (0%)
Ascites	0/179 (0%)		2/181 (1.1%)
Colitis	1/179 (0.6%)		0/181 (0%)
Constipation	1/179 (0.6%)		0/181 (0%)
Duodenal obstruction	2/179 (1.1%)		0/181 (0%)
Duodenal stenosis	2/179 (1.1%)		0/181 (0%)
Enteritis	0/179 (0%)		1/181 (0.6%)
Erosive oesophagitis	0/179 (0%)		1/181 (0.6%)
Gastric haemorrhage	1/179 (0.6%)		1/181 (0.6%)
Gastric stenosis	1/179 (0.6%)		0/181 (0%)
Gastric ulcer	0/179 (0%)		1/181 (0.6%)
Gastrointestinal haemorrhage	1/179 (0.6%)		1/181 (0.6%)
Intestinal obstruction	1/179 (0.6%)		0/181 (0%)
Mallory-Weiss syndrome	0/179 (0%)		1/181 (0.6%)
Nausea	3/179 (1.7%)		2/181 (1.1%)
Obstruction gastric	2/179 (1.1%)		0/181 (0%)
Pancreatitis	2/179 (1.1%)		0/181 (0%)
Pancreatitis acute	1/179 (0.6%)		0/181 (0%)
Vomiting	4/179 (2.2%)		3/181 (1.7%)
General disorders
Asthenia	3/179 (1.7%)		2/181 (1.1%)
Device occlusion	0/179 (0%)		1/181 (0.6%)
Fatigue	1/179 (0.6%)		0/181 (0%)
Oedema peripheral	0/179 (0%)		1/181 (0.6%)
Pyrexia	3/179 (1.7%)		3/181 (1.7%)
Sudden cardiac death	1/179 (0.6%)		0/181 (0%)
Sudden death	0/179 (0%)		1/181 (0.6%)
Hepatobiliary disorders
Bile duct obstruction	1/179 (0.6%)		1/181 (0.6%)
Bile duct stenosis	0/179 (0%)		2/181 (1.1%)
Cholangitis	2/179 (1.1%)		4/181 (2.2%)
Cholestasis	2/179 (1.1%)		6/181 (3.3%)
Jaundice	1/179 (0.6%)		1/181 (0.6%)
Jaundice cholestatic	2/179 (1.1%)		2/181 (1.1%)
Dilatation intrahepatic duct acquired	0/179 (0%)		1/181 (0.6%)
Hyperbilirubinaemia	0/179 (0%)		2/181 (1.1%)
Infections and infestations
Biliary sepsis	1/179 (0.6%)		4/181 (2.2%)
Biliary tract infection	1/179 (0.6%)		1/181 (0.6%)
Bronchitis	0/179 (0%)		1/181 (0.6%)
Bronchopneumonia	0/179 (0%)		1/181 (0.6%)
Cellulitis	0/179 (0%)		2/181 (1.1%)
Device related infection	1/179 (0.6%)		2/181 (1.1%)
Enterococcal bacteraemia	0/179 (0%)		1/181 (0.6%)
Erysipelas	0/179 (0%)		1/181 (0.6%)
Escherichia urinary tract infection	0/179 (0%)		1/181 (0.6%)
Infection	0/179 (0%)		1/181 (0.6%)
Liver abscess	0/179 (0%)		1/181 (0.6%)
Lobar pneumonia	0/179 (0%)		1/181 (0.6%)
Lymphangitis	0/179 (0%)		1/181 (0.6%)
Nasopharyngitis	0/179 (0%)		1/181 (0.6%)
Peritonitis	0/179 (0%)		1/181 (0.6%)
Peritonitis bacterial	1/179 (0.6%)		0/181 (0%)
Pneuomococcal sepsis	0/179 (0%)		1/181 (0.6%)
Pneumonia	2/179 (1.1%)		4/181 (2.2%)
Sepsis	2/179 (1.1%)		0/181 (0%)
Urinary tract infection	2/179 (1.1%)		2/181 (1.1%)
Viral upper respiratory tract infection	0/179 (0%)		1/181 (0.6%)
Infection (not confirmed) due to fever and elevated CRP	0/179 (0%)		1/181 (0.6%)
Injury, poisoning and procedural complications
Infusion related reaction	1/179 (0.6%)		0/181 (0%)
Intestinal anastomosis complication	1/179 (0.6%)		0/181 (0%)
Pneuomothorax traumatic	0/179 (0%)		1/181 (0.6%)
Investigations
Activated partial thromboplastin time prolonged	0/179 (0%)		1/181 (0.6%)
Alanine aminotransferase increased	0/179 (0%)		1/181 (0.6%)
Aspartate aminotransferase increased	0/179 (0%)		1/181 (0.6%)
Blood alkaline phosphatase increased	0/179 (0%)		1/181 (0.6%)
Blood bilirubin increased	0/179 (0%)		5/181 (2.8%)
C-reactive protein increased	1/179 (0.6%)		1/181 (0.6%)
Haemoglobin decreased	1/179 (0.6%)		0/181 (0%)
Platelet count decreased	1/179 (0.6%)		0/181 (0%)
Metabolism and nutrition disorders
Decreased appetite	1/179 (0.6%)		0/181 (0%)
Dehydration	5/179 (2.8%)		2/181 (1.1%)
Fluid retention	0/179 (0%)		1/181 (0.6%)
Hypercalcaemia	1/179 (0.6%)		0/181 (0%)
Hyperglycaemia	2/179 (1.1%)		1/181 (0.6%)
Hyperkalaemia	1/179 (0.6%)		0/181 (0%)
Hyperuricaemia	1/179 (0.6%)		0/181 (0%)
Hyponatraemia	1/179 (0.6%)		0/181 (0%)
Malnutrition	1/179 (0.6%)		0/181 (0%)
Type 1 diabetes mellitus	0/179 (0%)		1/181 (0.6%)
Musculoskeletal and connective tissue disorders
Back pain	2/179 (1.1%)		0/181 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma pancreas	1/179 (0.6%)		0/181 (0%)
Cancer pain	1/179 (0.6%)		0/181 (0%)
Malignant ascites	1/179 (0.6%)		0/181 (0%)
Malignant pleural effusion	1/179 (0.6%)		0/181 (0%)
Metastases to peritoneum	2/179 (1.1%)		0/181 (0%)
Pancreatic carcinoma metastatic	32/179 (17.9%)		39/181 (21.5%)
Tumour haemorrhage	0/179 (0%)		1/181 (0.6%)
Nervous system disorders
Cerebrovascular accident	3/179 (1.7%)		1/181 (0.6%)
Convulsion	0/179 (0%)		1/181 (0.6%)
Dizziness	1/179 (0.6%)		0/181 (0%)
Haemorrhage intracranial	0/179 (0%)		1/181 (0.6%)
Hypotonia	1/179 (0.6%)		0/181 (0%)
Ischaemic stroke	1/179 (0.6%)		0/181 (0%)
Syncope	1/179 (0.6%)		0/181 (0%)
Renal and urinary disorders
Acute prerenal failure	0/179 (0%)		1/181 (0.6%)
Hydronephrosis	1/179 (0.6%)		0/181 (0%)
Prerenal failure	0/179 (0%)		1/181 (0.6%)
Renal failure acute	1/179 (0.6%)		1/181 (0.6%)
Urinary retention	1/179 (0.6%)		0/181 (0%)
Renal failure	2/179 (1.1%)		1/181 (0.6%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/179 (0%)		1/181 (0.6%)
Couth	1/179 (0.6%)		0/181 (0%)
Dyspnoea	3/179 (1.7%)		2/181 (1.1%)
Epistaxis	1/179 (0.6%)		0/181 (0%)
Pleural effusion	0/179 (0%)		2/181 (1.1%)
Pneumonitis	0/179 (0%)		1/181 (0.6%)
Pneumothorax	0/179 (0%)		1/181 (0.6%)
Pulmonary embolism	4/179 (2.2%)		5/181 (2.8%)
Pulmonary fibrosis	0/179 (0%)		1/181 (0.6%)
Pulmonary oedema	2/179 (1.1%)		0/181 (0%)
Respiratory failure	2/179 (1.1%)		0/181 (0%)
Vascular disorders
Arterial thrombosis limb	9/179 (5%)		3/181 (1.7%)
Deep vein thrombosis	3/179 (1.7%)		2/181 (1.1%)
Hypertension	3/179 (1.7%)		0/181 (0%)
Thrombophlebitis	1/179 (0.6%)		0/181 (0%)
Venous thrombosis limb	1/179 (0.6%)		0/181 (0%)
Other (Not Including Serious) Adverse Events
	CO-1.01		Gemcitabine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	171/179 (95.5%)		164/181 (90.6%)
Blood and lymphatic system disorders
Anaemia	65/179 (36.3%)		78/181 (43.1%)
Thrombocytopenia	53/179 (29.6%)		60/181 (33.1%)
Neutropenia	46/179 (25.7%)		47/181 (26%)
Platelet count decreased	14/179 (7.8%)		10/181 (5.5%)
Leukopenia	12/179 (6.7%)		17/181 (9.4%)
Thrombocytosis	10/179 (5.6%)		1/181 (0.6%)
Gastrointestinal disorders
Nausea	70/179 (39.1%)		59/181 (32.6%)
Decreased appetite	42/179 (23.5%)		33/181 (18.2%)
Vomiting	41/179 (22.9%)		35/181 (19.3%)
Diarrhoea	34/179 (19%)		30/181 (16.6%)
Abdominal pain	32/179 (17.9%)		24/181 (13.3%)
Constipation	26/179 (14.5%)		25/181 (13.8%)
Abdominal pain upper	19/179 (10.6%)		29/181 (16%)
Ascites	7/179 (3.9%)		17/181 (9.4%)
General disorders
Asthenia	47/179 (26.3%)		34/181 (18.8%)
Fatigue	38/179 (21.2%)		45/181 (24.9%)
Pyrexia	35/179 (19.6%)		41/181 (22.7%)
Oedema peripheral	25/179 (14%)		34/181 (18.8%)
Hepatobiliary disorders
Hyperbilirubinaemia	11/179 (6.1%)		17/181 (9.4%)
Infections and infestations
Urinary tract infection	5/179 (2.8%)		11/181 (6.1%)
Investigations
Alanine aminotransferase increased	20/179 (11.2%)		15/181 (8.3%)
Aspartate aminotransferase increased	16/179 (8.9%)		19/181 (10.5%)
Weight decreased	14/179 (7.8%)		10/181 (5.5%)
Blood akaline phosphatase increased	11/179 (6.1%)		10/181 (5.5%)
Gamma-glutamyltransferase increased	9/179 (5%)		8/181 (4.4%)
Musculoskeletal and connective tissue disorders
Back pain	13/179 (7.3%)		16/181 (8.8%)
Nervous system disorders
Dizziness	11/179 (6.1%)		8/181 (4.4%)
Headache	11/179 (6.1%)		12/181 (6.6%)
Psychiatric disorders
Insomnia	13/179 (7.3%)		10/181 (5.5%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	18/179 (10.1%)		24/181 (13.3%)
Cough	12/179 (6.7%)		7/181 (3.9%)
Vascular disorders
Hypertension	7/179 (3.9%)		10/181 (5.5%)
Hypotension	5/179 (2.8%)		10/181 (5.5%)

Limitations/Caveats

Due to Primary endpoint showing lack of efficacy, development of CO-1.01 was stopped and secondary endpoints were not analyzed. However, patient enrollment completed normally.

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 120 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.