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Paclitaxel/Carboplatin With or Without Cetuximab in CUP (PACET-CUP)

Primary Purpose

Neoplasms, Unknown Primary, Carcinoma

Status
Unknown status
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
paclitaxel/carboplatin
cetuximab
Sponsored by
Heidelberg University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neoplasms, Unknown Primary focused on measuring carcinoma of unknown primary, cancer of unknown primary, CUP, carboplatin, paclitaxel, cetuximab

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Histologic or cytologic proven, non-resectable carcinoma of unknown primary (adenocarcinoma or non-differentiated carcinoma)
  • Measurable tumor lesion(s) according to RECIST criteria
  • WHO PS 0 to 1
  • Paclitaxel/Carboplatin with or without Cetuximab in Adeno- and Undifferentiated CUP (PACET-CUP)
  • Signed written informed consent
  • ≥ 18 years of age
  • Effective contraception for both male and female subjects if the risk of conception exists

  • Adequate bone marrow function:

    • Neutrophiles blood cell count (NBC) ≥ 1,5x109/L
    • Platelet count ≥ 100x109/L
    • Hemoglobin ≥ 5,00 mmol/L (8 g/dL)

  • Adequate liver and renal function:

    • Bilirubin ≤ 1,5 x upper normal level (UNL) and not increasing more than 25% within the last 4 weeks
    • ASAT and ALAT ≤ 2,5 x UNL or in case of liver metastases ≤ 5 x UNL
    • Serum creatinine ≤ 1.5 x UNL

Exclusion Criteria:

  • Previous exposure to epidermal growth factor receptor-targeting therapy
  • Previous chemotherapy except adjuvant treatment with progression of disease documented > 6 months after end of adjuvant treatment
  • Radiotherapy or major abdominal or thoracic surgery within the last 4 weeks before inclusion
  • Concurrent chronic systemic immunotherapy, chemotherapy or hormone therapy
  • Investigational agents or participation in clinical trials within 30 days before treatment start in this study
  • Clinically relevant coronary disease or myocardial infarction within 12 months before study entry
  • Possibility of a curative local treatment (surgery and/or radiotherapy)
  • Women with axillary node metastasis as predominant tumor site
  • Women with peritoneal carcinomatosis as predominant tumor site
  • Men < 50 years old with retroperitoneal or mediastinal lymph node +/- lung metastases as predominant tumor site
  • Identification of the primary or suspicion of a specific tumor entity by reference histopathology (i.e., Her-2 positive or hormone receptor positive tumors corresponding to breast cancer, CK7-negative/CK20- positive tumors with high probability for colorectal cancer)
  • Peripheral neuropathy > CTC grade I
  • Previous malignancy within the last 5 years (except history of basal cell carcinoma of skin or pre-invasive carcinoma of the cervix with adequate treatment)
  • History of severe psychiatric illness
  • Life expectancy less than six weeks
  • Drug or alcohol abuse
  • Known hypersensitivity reaction to any of the components of the study treatment
  • Pregnancy (absence to be confirmed by β-hCG test) or lactation period
  • Brain metastasis and/or leptomeningeal disease (known or suspected)
  • Acute or sub-acute intestinal occlusion or inflammatory bowel disease

Sites / Locations

  • University Hospital Heidelberg, Med. Dep. v

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

A

B

Arm Description

6 cycles of carboplatin/paclitaxel

carboplatin/paclitaxel plus cetuximab until disease progression

Outcomes

Primary Outcome Measures

The rate of progression free survival at 8 months after randomization, defined as the proportion of patients alive with stable disease, partial or complete response, according to RECIST is the primary endpoint for the final analysis.

Secondary Outcome Measures

Efficacy: Response rate, Median progression free survival (PFS), Overall survival (OS) Toxicity

Full Information

First Posted
May 6, 2009
Last Updated
May 13, 2009
Sponsor
Heidelberg University
Collaborators
Merck KGaA, Darmstadt, Germany
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1. Study Identification

Unique Protocol Identification Number
NCT00894569
Brief Title
Paclitaxel/Carboplatin With or Without Cetuximab in CUP
Acronym
PACET-CUP
Official Title
Open-Labeled, Randomized Multi-Center Phase II Study Evaluating the Efficacy and Safety of Paclitaxel/ Carboplatin With and Without Cetuximab as First-Line Treatment of Adeno- and Undifferentiated Carcinoma of Unknown Primary (CUP)
Study Type
Interventional

2. Study Status

Record Verification Date
May 2009
Overall Recruitment Status
Unknown status
Study Start Date
July 2009 (undefined)
Primary Completion Date
July 2010 (Anticipated)
Study Completion Date
August 2011 (Anticipated)

3. Sponsor/Collaborators

Name of the Sponsor
Heidelberg University
Collaborators
Merck KGaA, Darmstadt, Germany

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to determine whether an addition of cetuximab to carboplatin/paclitaxel can improve efficacy in comparison to carboplatin/paclitaxel in patients with carcinoma of unknown-primary.
Detailed Description
Carcinomas of unknown primary (CUP) account for approximately 2-5% of all cancer diagnoses. Except for some subsets with favorable prognosis, for most of these patients, treatment options are limited, and no standard first-line regimen has been identified. Standard therapy for patients with adeno- or undifferentiated CUP is Paclitaxel/Carboplatin, yielding response rates between 20-40%. In recent years, targeted therapies with inhibitors to EGFR, several tyrosine kinases, and VEGF have been shown to improve survival in different solid tumor entities. Cetuximab, a monoclonal antibody against the EGF receptor, has proved efficacy in combination with chemotherapy in patients with metastatic colorectal cancer, gastric cancer, squamous cell carcinoma of head and neck and non-small cell lung cancer (NSCLC). Because of these promising results it seems to be reasonable to examine the impact of adding cetuximab to standard chemotherapy with paclitaxel and carboplatin in patients with CUP.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neoplasms, Unknown Primary, Carcinoma
Keywords
carcinoma of unknown primary, cancer of unknown primary, CUP, carboplatin, paclitaxel, cetuximab

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
150 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
A
Arm Type
Active Comparator
Arm Description
6 cycles of carboplatin/paclitaxel
Arm Title
B
Arm Type
Experimental
Arm Description
carboplatin/paclitaxel plus cetuximab until disease progression
Intervention Type
Drug
Intervention Name(s)
paclitaxel/carboplatin
Intervention Description
6 cycles paclitaxel 175 mg/m² and carboplatin AUC 5, repetition d22.
Intervention Type
Drug
Intervention Name(s)
cetuximab
Intervention Description
cetuximab (400 mg/m² first dose, 250 mg/m² weekly) until disease progression
Primary Outcome Measure Information:
Title
The rate of progression free survival at 8 months after randomization, defined as the proportion of patients alive with stable disease, partial or complete response, according to RECIST is the primary endpoint for the final analysis.
Time Frame
8 months after randomization
Secondary Outcome Measure Information:
Title
Efficacy: Response rate, Median progression free survival (PFS), Overall survival (OS) Toxicity
Time Frame
until end of study

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologic or cytologic proven, non-resectable carcinoma of unknown primary (adenocarcinoma or non-differentiated carcinoma) Measurable tumor lesion(s) according to RECIST criteria WHO PS 0 to 1 Paclitaxel/Carboplatin with or without Cetuximab in Adeno- and Undifferentiated CUP (PACET-CUP) Signed written informed consent ≥ 18 years of age Effective contraception for both male and female subjects if the risk of conception exists Adequate bone marrow function: Neutrophiles blood cell count (NBC) ≥ 1,5x109/L Platelet count ≥ 100x109/L Hemoglobin ≥ 5,00 mmol/L (8 g/dL) Adequate liver and renal function: Bilirubin ≤ 1,5 x upper normal level (UNL) and not increasing more than 25% within the last 4 weeks ASAT and ALAT ≤ 2,5 x UNL or in case of liver metastases ≤ 5 x UNL Serum creatinine ≤ 1.5 x UNL Exclusion Criteria: Previous exposure to epidermal growth factor receptor-targeting therapy Previous chemotherapy except adjuvant treatment with progression of disease documented > 6 months after end of adjuvant treatment Radiotherapy or major abdominal or thoracic surgery within the last 4 weeks before inclusion Concurrent chronic systemic immunotherapy, chemotherapy or hormone therapy Investigational agents or participation in clinical trials within 30 days before treatment start in this study Clinically relevant coronary disease or myocardial infarction within 12 months before study entry Possibility of a curative local treatment (surgery and/or radiotherapy) Women with axillary node metastasis as predominant tumor site Women with peritoneal carcinomatosis as predominant tumor site Men < 50 years old with retroperitoneal or mediastinal lymph node +/- lung metastases as predominant tumor site Identification of the primary or suspicion of a specific tumor entity by reference histopathology (i.e., Her-2 positive or hormone receptor positive tumors corresponding to breast cancer, CK7-negative/CK20- positive tumors with high probability for colorectal cancer) Peripheral neuropathy > CTC grade I Previous malignancy within the last 5 years (except history of basal cell carcinoma of skin or pre-invasive carcinoma of the cervix with adequate treatment) History of severe psychiatric illness Life expectancy less than six weeks Drug or alcohol abuse Known hypersensitivity reaction to any of the components of the study treatment Pregnancy (absence to be confirmed by β-hCG test) or lactation period Brain metastasis and/or leptomeningeal disease (known or suspected) Acute or sub-acute intestinal occlusion or inflammatory bowel disease
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Alwin Kraemer, Prof.
Phone
+49-6221-42-1441
Email
a.kraemer@dkfz.de
First Name & Middle Initial & Last Name or Official Title & Degree
Katharina Schuette, Dr.
Phone
+49-351-458-2311
Email
katharina.schuette@uniklinikum-dresden.de
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alwin Kraemer, Prof. Dr.
Organizational Affiliation
University of Heidelberg, Medic. Dep. V
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital Heidelberg, Med. Dep. v
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kraemer
Phone
+49-6221-42-1441
Email
a.kraemer@dkfz.de
First Name & Middle Initial & Last Name & Degree
Alwin Kraemer, Prof. Dr.

12. IPD Sharing Statement

Citations:
PubMed Identifier
33235314
Citation
Folprecht G, Trautmann K, Stein A, Huebner G, Stahl M, Kasper S, Kretzschmar A, Kohne CH, Grunwald V, Hofheinz RD, Schutte K, Loffler H, Bokemeyer C, Kramer A; Arbeitsgemeinschaft Internistische Onkologie (AIO) - CUP Group. Adding cetuximab to paclitaxel and carboplatin for first-line treatment of carcinoma of unknown primary (CUP): results of the Phase 2 AIO trial PACET-CUP. Br J Cancer. 2021 Feb;124(4):721-727. doi: 10.1038/s41416-020-01141-8. Epub 2020 Nov 25.
Results Reference
derived

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Paclitaxel/Carboplatin With or Without Cetuximab in CUP

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