Chemotherapy With or Without Enoxaparin in Pancreatic Cancer

NCT ID: NCT00785421

Last Updated: 2015-01-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 312 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-04-30
• Study Completion Date: 2009-06-30

Brief Summary

To evaluate the safety and efficacy of chemotherapy with or without enoxaparin. This study is powered to decrease the DVT/ VTE events rate from 10% to 3% with enoxaparin in the experimental arm.

N=540pts, dropout-rate 15%, power 80 %, two sided, significant level 5%

Detailed Description

Approximately 20% of patients (pts) diagnosed with pancreatic adenocarcinoma (PA) develop venous thromboembolism, which may contribute to the dismal prognosis of PA. A small phase II trial suggested an improved survival by the addition of low molecular weight heparin (LMWH) to chemotherapy. We conducted a small pilot study which indicated that the addition of enoxaparin to chemotherapy GFFC chemotherapy is safe and feasible in pts with advanced PA. Furthermore, results of several phase III studies suggest that pts in good performance status may benefit from more intensive chemotherapy regimen (Riess et al; Heinemann et al; ASCO 2005). Based on these considerations we started the multicenter phase III study CONKO 004.

540 patients are to be recruited into this study. Primary stratification takes place according to Karnofsky performance status and kidney function. Patients with KPS > 80% and normal kidney function receive GFFC +/- LMWH (gemcitabine 1 g/m2 (30 min), cisplatin 30 mg/m2 (90 min), 5-fluorouracil 750 mg/m2 (24 h), folinic acid 200 mg/m2 (30 min), d1, 8; q3w +/- Enoxaparin 1mg/kg daily s.c.). Pts with KPS < 80 % and increased creatinin plasma levels (>1.3 mg/dl) receive the current standard therapy (gemcitabine 1 g/m2 (30 min), d1, 8, 15; q4w) +/- LMWM +/- Enoxaparin 1mg/kg daily s.c. After 12 weeks of initial chemotherapy all patients who have not progressed received the standard therapy (gemcitabine mono) +/- Enoxaparin 40mg/d s.c.

Conditions

Pancreatic Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

A

Patients with KPS > 80% and normal kidney function receive GFFC + LMWH (gemcitabine 1 g/m2 (30 min), cisplatin 30 mg/m2 (90 min), 5-fluorouracil 750 mg/m2 (24 h), folinic acid 200 mg/m2 (30 min), d1, 8; q3w +/- Enoxaparin 1mg/kg daily s.c.).

Pts with KPS < 80 % and increased creatinin plasma levels (>1.3 mg/dl) receive the current standard therapy (gemcitabine 1 g/m2 (30 min), d1, 8, 15; q4w) + Enoxaparin 1mg/kg daily s.c.

After 12 weeks of initial chemotherapy all patients who have not progressed received the standard therapy (gemcitabine mono) + Enoxaparin 40mg/d s.c.

Group Type: EXPERIMENTAL

enoxaparin

Intervention Type: DRUG

Patients receive GFFC +/- LMWH (gemcitabine 1 g/m2 (30 min), cisplatin 30 mg/m2 (90 min), 5-fluorouracil 750 mg/m2 (24 h), folinic acid 200 mg/m2 (30 min), d1, 8; q3w +/- Enoxaparin 1mg/kg daily s.c.). Pts with KPS \< 80 % and increased creatinin plasma levels (\>1.3 mg/dl) receive the current standard therapy (gemcitabine 1 g/m2 (30 min), d1, 8, 15; q4w) +/- LMWM +/- Enoxaparin 1mg/kg daily s.c. After 12 weeks of initial chemotherapy all patients who have not progressed received the standard therapy (gemcitabine mono) +/- Enoxaparin 40mg/d s.c.

chemotherapy with LMWH - enoxaparin

Intervention Type: DRUG

1-12 weeks: enoxaparin 1g/m², s.c. 12-PD or event: enoxaparin 0,4g s.c.

B

Patients with KPS > 80% and normal kidney function receive GFFC - LMWH (gemcitabine 1 g/m2 (30 min), cisplatin 30 mg/m2 (90 min), 5-fluorouracil 750 mg/m2 (24 h), folinic acid 200 mg/m2 (30 min), d1, 8; q3w - Enoxaparin 1mg/kg daily s.c.).

Pts with KPS < 80 % and increased creatinin plasma levels (>1.3 mg/dl) receive the current standard therapy (gemcitabine 1 g/m2 (30 min), d1, 8, 15; q4w) - Enoxaparin 1mg/kg daily s.c.

After 12 weeks of initial chemotherapy all patients who have not progressed received the standard therapy (gemcitabine mono) - Enoxaparin 40mg/d s.c.

Group Type: ACTIVE_COMPARATOR

only chemotherapy

Intervention Type: DRUG

observation, no treatment with LMWH

Interventions

enoxaparin

Patients receive GFFC +/- LMWH (gemcitabine 1 g/m2 (30 min), cisplatin 30 mg/m2 (90 min), 5-fluorouracil 750 mg/m2 (24 h), folinic acid 200 mg/m2 (30 min), d1, 8; q3w +/- Enoxaparin 1mg/kg daily s.c.). Pts with KPS \< 80 % and increased creatinin plasma levels (\>1.3 mg/dl) receive the current standard therapy (gemcitabine 1 g/m2 (30 min), d1, 8, 15; q4w) +/- LMWM +/- Enoxaparin 1mg/kg daily s.c. After 12 weeks of initial chemotherapy all patients who have not progressed received the standard therapy (gemcitabine mono) +/- Enoxaparin 40mg/d s.c.

Intervention Type: DRUG

chemotherapy with LMWH - enoxaparin

1-12 weeks: enoxaparin 1g/m², s.c. 12-PD or event: enoxaparin 0,4g s.c.

Intervention Type: DRUG

only chemotherapy

observation, no treatment with LMWH

Intervention Type: DRUG

Other Intervention Names

gemcitabine; cisplatin; folinic acid; 5-FU; gemcitabine; cisplatin; folinic acid; 5-FU; gemcitabin; cisplatin; folinic acid; 5-FU

Eligibility Criteria

Inclusion Criteria

• histological or cytological pancreatic carcinoma, stage IV A, b
• no preceding radio or chemotherapy of the primarius or the reference lesions
• Karnofsky performance status ≥ 60%
• measurable tumor lesion by spiral CT or MRT not older than 14 days
• no deep venous thrombosis within the last 2 years
• patient compliance and geographical proximity of the residence, which make an adequate follow up possible
• sufficient bone marrow reserve: leukocyte ≥ 3.5 × 109 /l, thrombocyte ≥ 100 × 109 /l
• signed informed consent
• minimum age of 18 years
• women/men must provide sufficient pregnancy prevention

Exclusion Criteria

• preexisting indication for anti-coagulation of other reason
• bleeding in the last 2 weeks or increased bleeding risk (e.g. serious coagulating disturbance, active stomach or intestine ulzera, or had operational interferences in the last 2 weeks)
• body weight < 45 kg and/or > 100 kg
• pregnancy or insufficient preventing methods in the study process
• serious illness, which are incompatible with a study participation
• hypersensitivity to study drugs
• patients with serious kidney malfunction (Creatininclearance < 30 ml/min)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: collaborator

Amgen

INDUSTRY

Sponsor Role: collaborator

Eli Lilly and Company

INDUSTRY

Sponsor Role: collaborator

CONKO-Studiengruppe

OTHER

Sponsor Role: lead

Responsible Party

Uwe Pelzer MD

Dr. med. Uwe Pelzer

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Hanno Riess, PHD

Role: STUDY_DIRECTOR

CONKO Study Group

Locations

Universitätsmedizin - Berlin - Charite

Berlin, State of Berlin, Germany

Countries

Germany

References

Rutjes AW, Porreca E, Candeloro M, Valeriani E, Di Nisio M. Primary prophylaxis for venous thromboembolism in ambulatory cancer patients receiving chemotherapy. Cochrane Database Syst Rev. 2020 Dec 18;12(12):CD008500. doi: 10.1002/14651858.CD008500.pub5.

Reference Type: DERIVED

PMID: 33337539 (View on PubMed)

Other Identifiers

CCT-NAPN-16752

Identifier Type: -

Identifier Source: secondary_id

CONKO 004

Identifier Type: -

Identifier Source: org_study_id