Maintenance Therapy With 5-FU/FA Plus Panitumumab vs. 5-FU/FA Alone After Prior Induction and Re-induction After Progress for 1st-line Treatment of Metastatic Colorectal Cancer

NCT01991873 | Completed Phase 2 DMC

• 3 other identifiers: AIO-KRK-02122012-005422-30PanaMa_DE-2009-0003
• Study Type: interventional
• Target: 387
• Locations: 1 country
• Sites: 2

Brief Summary

This is a phase II, randomized, multi-center, open-label, parallel-group study to evaluate the progression-free survival during maintenance therapy. Eligible patients will be treated within a 12-week induction therapy. Those patients achieving CR/PR or SD at 12 weeks and qualifying for maintenance treatment and re-induction treatment with all potential drug components, will be randomized in a ratio of 1:1 to receive chemotherapy plus panitumumab or chemotherapy alone during maintenance. In case of progression, re-induction treatment will be started.

Conditions

Metastatic Colorectal Cancer

Keywords

metastatic colorectal cancer; maintenance therapy; Panitumumab; Vectibix®

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  Progression-free survival during maintenance therapy defined as time from randomization until disease progression or death, whatever occurs first.

  Until end of follow-up (24 months after randomization)

Secondary Outcomes (7)

• failure of treatment strategy

  Until end of follow up (24 months after randomization)

• Progression-free survival of re-induction

  From start of re-induction therapy until progress or end of follow-up (24 months after randomization)

• Objective response after 12 weeks of induction chemotherapy

  12 weeks after start of induction chemotherapy

• Objective best response during maintenance and re-induction

  Start of maintenance- until end of re-inductin therapy (expected average of 8 months)

• Overall survival

  Until end of follow-up (24 months after randomization)

Study Arms (2)

Maintenance Chemotherapy + Panitumumab

EXPERIMENTAL

Maintenance therapy: Panitumumab 6 mg/kg prior to administration of chemotherapy Folinic acid 400 mg/m2 over 2 hours on day 1 5-FU 2400mg/m2 46h continuous infusion day 1 - day 2 Repeat on day 15 Re-induction upon progression: Panitumumab 6 mg/kg prior to administration of mFOLFOX6 chemotherapy. mFOLFOX6: Oxaliplatin 85 mg/m2 over 2 hours on day 1 Folinic acid 400 mg/m2 over 2 hours on day 1 5-FU 2400mg/m2 46h continuous infusion day 1 - day 2 Repeat on day 15

Drug: Maintenance Chemotherapy; Drug: Panitumumab (Within maintenance phase); Drug: mFOLFOX6 (Within re-induction phase); Drug: Panitumumab (Within re-induction phase)

Maintenance Chemotherapy w/o Panitumumab

EXPERIMENTAL

Maintenance therapy: Folinic acid 400 mg/m2 over 2 hours on day 1 5-FU 2400mg/m2 46h continuous infusion day 1 - day 2 Repeat on day 15 Re-induction upon progression: Panitumumab 6 mg/kg prior to administration of mFOLFOX6 chemotherapy. mFOLFOX6 chemotherapy: Oxaliplatin 85 mg/m2 over 2 hours on day 1 Folinic acid 400 mg/m2 over 2 hours on day 1 5-FU 2400mg/m2 46h continuous infusion day 1 - day 2 Repeat on day 15

Drug: Maintenance Chemotherapy; Drug: mFOLFOX6 (Within re-induction phase); Drug: Panitumumab (Within re-induction phase)

Interventions

Maintenance Chemotherapy DRUG

Also known as: Folinic acid + 5-FU (5-Fluorouracil)

Maintenance Chemotherapy + Panitumumab; Maintenance Chemotherapy w/o Panitumumab

Panitumumab (Within maintenance phase) DRUG

Also known as: Vectibix

Maintenance Chemotherapy + Panitumumab

mFOLFOX6 (Within re-induction phase) DRUG

Also known as: Oxaliplatin + Folinic acid + 5-FU (5-Fluorouracil)

Maintenance Chemotherapy + Panitumumab; Maintenance Chemotherapy w/o Panitumumab

Panitumumab (Within re-induction phase) DRUG

Also known as: Vectibix

Maintenance Chemotherapy + Panitumumab; Maintenance Chemotherapy w/o Panitumumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed written informed consent
• Male or female ≥ 18 years of age
• Histologically proven metastatic colorectal cancer
• Molecular testing showing RAS wild-type in colorectal carcinoma cells
• Life expectancy \> 12 weeks
• At least one measurable lesion according to RECIST 1.1
• Adequate bone marrow, liver, kidney, organ and metabolic function
• Bone marrow function:
• leukocyte count ≥ 3.0 × 109/L
• ANC ≥ 1.5 × 109/L
• platelet count ≥ 100 × 109/L
• hemoglobin ≥ 9 g/dL or 5.59 mmol/L (may be transfused or treated with erythropoietin to maintain/ exceed this level)
• Hepatic function:
• Total bilirubin ≤ 1.5 × UNL
• ALT and AST ≤ 2.5 × UNL (or ≤ 5 × UNL in presence of liver metastases)

You may not qualify if:

• Previous treatment for colorectal cancer in the metastatic setting
• Previous EGFR-targeting therapy \< 6 months after end of adjuvant therapy
• Known brain metastases unless adequately treated (surgery or radiotherapy) with no evidence of progression and neurologically stable off anticonvulsants and steroids
• Chronic inflammatory bowel disease
• Peripheral neuropathy ≥ NCI-CTCAE V 4.03 grade 2
• Other previous malignancies with the exception of a history of previous curatively treated basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix or other curatively treated malignant disease without recurrence after at least 5 years of follow-up
• Significant disease that, in the investigator's opinion, would exclude the patient from the study
• History of cardiac disease; defined as:
• Congestive heart failure \> New York Heart Association (NYHA) class 2
• Active coronary artery disease (myocardial infarction more than 6 months prior to start of study treatment is allowed)
• Cardiac arrhythmias requiring anti-arrhythmic therapy (beta-blockers or digoxin are permitted)
• Uncontrolled hypertension (defined as blood pressure ≥ 160 mmHg systolic and/or ≥ 90 mmHg diastolic on medication)
• Patients with interstitial lung disease, e.g., pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest CT scan
• Known HIV, hepatitis B or C infection
• Known hypersensitivity reaction to any of the study components

Sponsors & Collaborators

• AIO-Studien-gGmbH: lead
• ClinAssess GmbH: collaborator
• Amgen: collaborator

Study Sites (2)

St.-Antonius-Hospital Eschweiler

Eschweiler, 52249, Germany

Location

Zentrum für Tumorbiologie und Integrative Medizin, Klinikum Wilhelmshaven

Wilhelmshaven, 26389, Germany

Location

Related Publications (8)

• Stahler A, Modest DP, Stintzing S, Borelli B, Keller T, Held S, Fischer von Weikersthal L, Muller L, Graeven U, Decker T, Heintges T, Kahl C, Hoppe B, Kiani A, Kaiser F, Schwaner I, Fruehauf S, Karthaus M, Trarbach T, Klauschen F, Horst D, Cremolini C, Heinemann V. Individual Patient Data Meta-Analysis of Consensus Molecular Subtypes as Biomarkers of First-Line Treatment in RAS Wild-Type Metastatic Colorectal Cancer. J Clin Oncol. 2026 Jan;44(1):31-41. doi: 10.1200/JCO-25-00596. Epub 2025 Nov 18.

  PMID: 41252656 DERIVED

• Ballhausen A, Swoboda S, Horst D, Fruehauf S, Graeven U, Muller L, Trarbach T, Fischer von Weikersthal L, Goekkurt E, Heinemann V, Kasper S, Kurreck A, Alig AHS, Reinacher-Schick AC, Bullinger L, Stahler A, Stintzing S, Jarosch A, Modest DP. Spatial Tumor Immune Microenvironment as a Prognostic and Predictive Biomarker in Anti-EGFR-Based Maintenance for RAS wt Metastatic CRC-The PanaMa (AIO KRK0212) Trial. Clin Cancer Res. 2025 Oct 1;31(19):4049-4058. doi: 10.1158/1078-0432.CCR-25-0879.

  PMID: 40736443 DERIVED

• Stahler A, Karthaus M, Fruehauf S, Graeven U, Muller L, Fischer von Weikersthal L, Caca K, Goekkurt E, Ballhausen A, Sommerhauser G, Alig AHS, Held S, Jarosch A, Horst D, Reinacher-Schick A, Kasper S, Heinemann V, Stintzing S, Trarbach T, Modest DP. Panitumumab plus 5-fluorouracil and folinic acid or 5-fluorouracil and folinic acid alone as maintenance therapy in RAS wild-type metastatic colorectal cancer (PanaMa, AIO KRK 0212): final efficacy analysis of a randomised, open-label, phase 2 trial. EClinicalMedicine. 2024 Dec 16;79:103004. doi: 10.1016/j.eclinm.2024.103004. eCollection 2025 Jan.

  PMID: 39802302 DERIVED

• Stahler A, Kind AJ, Sers C, Mamlouk S, Muller L, Karthaus M, Fruehauf S, Graeven U, Fischer von Weikersthal L, Sommerhauser G, Kasper S, Hoppe B, Kurreck A, Held S, Heinemann V, Horst D, Jarosch A, Stintzing S, Trarbach T, Modest DP. Negative Hyperselection of Resistance Mutations for Panitumumab Maintenance in RAS Wild-Type Metastatic Colorectal Cancer (PanaMa Phase II Trial, AIO KRK 0212). Clin Cancer Res. 2024 Apr 1;30(7):1256-1263. doi: 10.1158/1078-0432.CCR-23-3023.

  PMID: 38289994 DERIVED

• Ballhausen A, Karthaus M, Fruehauf S, Graeven U, Muller L, Konig AO, von Weikersthal LF, Sommerhauser G, Alig AHS, Goekkurt E, Meyer-Knees JW, Kurreck A, Stahler A, Held S, Kasper S, Heinrich K, Heinemann V, Stintzing S, Trarbach T, Modest DP. Health-related quality of life in patients with RAS wild-type metastatic colorectal cancer treated with fluorouracil and folinic acid with or without panitumumab as maintenance therapy: a prespecified secondary analysis of the PanaMa (AIO KRK 0212) trial. Eur J Cancer. 2023 Sep;190:112955. doi: 10.1016/j.ejca.2023.112955. Epub 2023 Jun 28.

  PMID: 37454537 DERIVED

• Stahler A, Hoppe B, Na IK, Keilholz L, Muller L, Karthaus M, Fruehauf S, Graeven U, Fischer von Weikersthal L, Goekkurt E, Kasper S, Kind AJ, Kurreck A, Alig AHS, Held S, Reinacher-Schick A, Heinemann V, Horst D, Jarosch A, Stintzing S, Trarbach T, Modest DP. Consensus Molecular Subtypes as Biomarkers of Fluorouracil and Folinic Acid Maintenance Therapy With or Without Panitumumab in RAS Wild-Type Metastatic Colorectal Cancer (PanaMa, AIO KRK 0212). J Clin Oncol. 2023 Jun 1;41(16):2975-2987. doi: 10.1200/JCO.22.02582. Epub 2023 Apr 5.

  PMID: 37018649 DERIVED

• Sommerhauser G, Kurreck A, Beck A, Fehrenbach U, Karthaus M, Fruehauf S, Graeven U, Mueller L, Koenig AO, V Weikersthal LF, Goekkurt E, Haas S, Stahler A, Heinemann V, Held S, Alig AHS, Kasper S, Stintzing S, Trarbach T, Modest DP. Depth of response of induction therapy and consecutive maintenance treatment in patients with RAS wild-type metastatic colorectal cancer: An analysis of the PanaMa trial (AIO KRK 0212). Eur J Cancer. 2023 Jan;178:37-48. doi: 10.1016/j.ejca.2022.09.011. Epub 2022 Oct 25.

  PMID: 36399909 DERIVED

• Modest DP, Karthaus M, Fruehauf S, Graeven U, Muller L, Konig AO, Fischer von Weikersthal L, Caca K, Kretzschmar A, Goekkurt E, Haas S, Kurreck A, Stahler A, Held S, Jarosch A, Horst D, Reinacher-Schick A, Kasper S, Heinemann V, Stintzing S, Trarbach T. Panitumumab Plus Fluorouracil and Folinic Acid Versus Fluorouracil and Folinic Acid Alone as Maintenance Therapy in RAS Wild-Type Metastatic Colorectal Cancer: The Randomized PANAMA Trial (AIO KRK 0212). J Clin Oncol. 2022 Jan 1;40(1):72-82. doi: 10.1200/JCO.21.01332. Epub 2021 Sep 17.

  PMID: 34533973 DERIVED

Related Links

• Homepage of the AIO (Arbeitsgemeinschaft Internistische Onkologie in der Deutschen Krebsgesellschaft e.V.)

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Maintenance Chemotherapy; Leucovorin; Fluorouracil; Panitumumab; Oxaliplatin

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Drug Therapy; Therapeutics; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals

Study Officials

• Tanja Trarbach, Dr. med.

  Zentrum für Tumorbiologie und Integrative Medizin, Klinikum Wilhelmshaven

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2013
• First Posted: November 25, 2013
• Study Start: April 1, 2014
• Primary Completion: February 18, 2023
• Study Completion: February 18, 2023
• Last Updated: June 15, 2023

Record last verified: 2023-06

Locations

DE (2)