SIEGE: Scheduling Nab-paclitaxel With Gemcitabine

Sponsor

CCTU- Cancer Theme (Other)

Overall Status

Completed

CT.gov ID

NCT03529175

Collaborator

Celgene (Industry)

146

Enrollment

Locations

Arms

Duration (Months)

6.3

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Metastatic pancreatic cancer is difficult to treat. Until recently, most patients would be offered treatment with a chemotherapy drug called gemcitabine. However, a large international trial showed that combining gemcitabine with a drug called nab-paclitaxel (or abraxane) was more effective compared with gemcitabine alone. The purpose of this study is to compare two different ways of combining gemcitabine with abraxane. Conventionally, both drugs are given on the same day via a drip into a vein in the arm but research suggests that giving abraxane 24 hours in advance of gemcitabine could possibly be more beneficial.

In this study, blood and tumour samples will be collected and analysed to try to confirm what has been seen in the laboratory studies. In addition, the investigators wish to find out whether certain tumour characteristics (called biomarkers) can be used to predict for response to chemotherapy.

Condition or Disease	Intervention/Treatment	Phase
Pancreatic Adenocarcinoma Metastatic	Drug: Abraxane (nab-paclitaxel) Drug: Gemcitabine	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

146 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Randomised Phase II Trial to Investigate Two Different Schedules of Nab-paclitaxel (Abraxane) Combined With Gemcitabine as First Line Treatment for Metastatic Pancreatic Ductal Adenocarcinoma

Study Start Date :

Jan 1, 2014

Actual Primary Completion Date :

Jun 1, 2016

Actual Study Completion Date :

Jun 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Concomitant Intravenous Abraxane125 mg/m2 30-minute infusion followed immediately by intravenous Gemcitabine 1000 mg/m2 30-minute infusion will be administered on days 1, 8 and 15 of a 4-week cycle.	Drug: Abraxane (nab-paclitaxel) Drug: Gemcitabine
Active Comparator: Sequential Intravenous Abraxane 125 mg/m2 30-minute infusion will be administered on days 1, 8 and 15 of a 4-week cycle. Intravenous Gemcitabine 1000 mg/m2 30-minute infusion will be administered on days 2, 9 and 16 of a 4-week cycle. Gemcitabine must be delivered 24 +/- 2 hours after commencing Abraxane infusion.	Drug: Abraxane (nab-paclitaxel) Drug: Gemcitabine

Arm

Intervention/Treatment

Active Comparator: Concomitant

Intravenous Abraxane125 mg/m2 30-minute infusion followed immediately by intravenous Gemcitabine 1000 mg/m2 30-minute infusion will be administered on days 1, 8 and 15 of a 4-week cycle.

Drug: Abraxane (nab-paclitaxel)

Drug: Gemcitabine

Active Comparator: Sequential

Intravenous Abraxane 125 mg/m2 30-minute infusion will be administered on days 1, 8 and 15 of a 4-week cycle. Intravenous Gemcitabine 1000 mg/m2 30-minute infusion will be administered on days 2, 9 and 16 of a 4-week cycle. Gemcitabine must be delivered 24 +/- 2 hours after commencing Abraxane infusion.

Drug: Abraxane (nab-paclitaxel)

Drug: Gemcitabine

Outcome Measures

Primary Outcome Measures

Progression free survival [From participant randomisation to the point at which disease progression is reported (i.e. 12 months)]
The primary objective of the trial is to investigate the outcome of sequential administration of nab-paclitaxel combined with gemcitabine (ABX/GEM, 24 hours apart) in patients with metastatic pancreatic ductal adenocarcinoma (PDAC) in terms of progression-free survival.

Secondary Outcome Measures

Patient Safety [1 year after end of treatment visit]
Adverse Events (including Serious Adverse Events), abnormal laboratory test results and performance status
Treatment Efficacy [8 weeks]
response to treatment assessed using radiological RECIST criteria

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Aged ≥ 18 years old
Signed informed consent and ability to comply with the protocol
Histologically or cytologically confirmed metastatic PDAC
Radiologically confirmed stage IV disease and measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1; baseline tumour assessments and measurements must be done within 28 days prior to randomisation
Karnofsky performance status ≥70%
Life expectancy >12 weeks from the date of screening assessment
Adequate bone marrow function
Absolute neutrophil count (ANC) ≥1.5 x 109 /L
Haemoglobin (Hb) ≥ 100 g/L
Platelets ≥100 x 109 /L
White blood cell count (WBC) ≥ 3 x 109 /L
Adequate liver function
Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤2.5 x upper limit of normal range (ULN)
Total bilirubin <1.5 x ULN
Adequate renal function defined as a serum creatinine ≤1.5 x ULN or calculated creatinine clearance by Cockcroft-Gault of ≥50 mL/min
Received no prior systemic therapy for metastatic disease
Prior adjuvant chemotherapy (with GEM or any other drug/s) is allowed if completed at least 6 months previously
Prior radiotherapy is allowed as long as there is measurable disease which has not been irradiated
Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, completion of QoL and HE questionnaires and other study procedures
Confirmation of tumour tissue sample collected within 12 weeks prior to randomisation and blood to be taken prior to randomisation
Women of child-bearing potential (WCBP), defined as a sexually mature woman not surgically sterilized or not post-menopausal for at least 24 consecutive months if age ≤55 years or 12 months if age >55 years, must have a negative serum or urine pregnancy test within 14 days prior to randomisation
All WCBP and all sexually active male patients must agree to use effective contraception methods throughout the study and for 30 days after the final dose of study drug for WCBP and for up to 6 months after treatment for male patients

Exclusion Criteria:

Patients with operable or locally advanced PDAC
Other invasive malignancies diagnosed within the last 5 years, except non-melanoma skin cancer and localized cured prostate cancer
Significant acute or chronic medical or psychiatric condition, disease or laboratory abnormality which in the judgment of the investigator would place the patient at undue risk or interfere with the trial. Examples include, but are not limited to:
Patients who have had a venous thromboembolic event who are not appropriately anticoagulated or have had a significant bleeding episode in the 3 weeks prior to randomisation
Patients with symptoms of severe chronic obstructive airways disease or significant shortness of breath at rest AND have an FEV1<1.0 L within the last 6 months
Patients with a history of interstitial lung disease, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis, cystic fibrosis or bronchiectasis
Patients with uncontrolled ischaemic heart or other cardiovascular event (myocardial infarction (MI), new angina, stroke transient ischaemic attack (TIA), or new congestive cardiac failure (CCF)) within the last 6 months
Patients with stable but significant cardiovascular disease defined by heart failure (New York Heart Association Functional Classification (NYHF) III or IV, see Appendix 3) or frequent angina
Presence of active infection
Cirrhotic liver disease, known chronic active or acute hepatitis B, or hepatitis C
Known allergy or hypersensitivity to GEM or ABX
Women who are pregnant, plan to become pregnant or are lactating
Routine use of any of the following will exclude patients:
Oral anti-oxidant supplements: beta-carotene, selenium, lutein, zeaxanthin, lycopene, pycnogenol, fernblock, omega-3S, vitamin C, vitamin E, astaxanthin

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cambridge University Hospitals NHS Foundation Trust	Cambridge	Cambridgeshire	United Kingdom	CB2 0QQ
2	Peterborough City Hospital	Peterborough	Cambridgeshire	United Kingdom	PE3 9GZ
3	Ysbyty Gwynedd	Bangor		United Kingdom
4	Belfast City Hospital	Belfast		United Kingdom	BT9 7AB
5	Queen Elizabeth Hospital	Birmingham		United Kingdom
6	Bristol Haematology & Oncology Centre	Bristol		United Kingdom
7	Velindre Cancer Centre	Cardiff		United Kingdom
8	Colchester Hospital	Colchester		United Kingdom	CO4 5JL
9	University Hospitals Coventry & Warwickshire	Coventry		United Kingdom	CV2 2DX
10	Edinburgh Cancer Research Centre	Edinburgh		United Kingdom
11	The Beatson Oncology Centre	Glasgow		United Kingdom
12	The Royal Surrey County Hospital	Guildford		United Kingdom
13	St James' Institute of Oncology	Leeds		United Kingdom
14	Leicester Royal Infirmary	Leicester		United Kingdom	LE1 5WW
15	Clatterbridge Cancer Centre	Liverpool		United Kingdom
16	Barts Health NHS Trust	London		United Kingdom	EC1A 7BE
17	Hammersmith Hospital	London		United Kingdom
18	The Royal Free Hospital	London		United Kingdom
19	University College London Hospital	London		United Kingdom
20	The Christie Hospital	Manchester		United Kingdom
21	Churchill Hospital	Oxford		United Kingdom
22	Weston Park Hospital	Sheffield		United Kingdom
23	Royal Cornwall Hospital	Truro		United Kingdom