mFOLFOX6 vs. mFOLFOX6 + Aflibercept as Neoadjuvant Treatment in MRI-defined T3-rectal Cancer

NCT03043729 | Completed Phase 2

• 1 other identifier: AIO-KRK-0214
• Study Type: interventional
• Target: 119
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with locally advanced rectal or rectosigmoid cancer staged cT3 CRM-negative with MRI will receive 6 cycles of neoadjuvant treatment with mFOLFOX6 (Arm A) vs. mFOLFOX6 + aflibercept (Arm B) followed by surgery.

Conditions

Rectal Cancer; Rectosigmoid Cancer

Keywords

neoadjuvant; MRI-defined T3; mFOLFOX6; Aflibercept

Outcome Measures

Primary Outcomes (1)

• Pathologic complete response (pCR)

  number of patients with a pCR finding divided by the number of patients in the analysis set pCR will be assessed in a standardized manner independently by a central pathology

  20 weeks

Secondary Outcomes (20)

• Dose intensities of study medication

  12 weeks

• Type, incidence and severity of AEs, SAEs

  20 weeks

• Dose reduction or discontinuation of study drug due to adverse events

  20 weeks

• Rate of treatment discontinuation due to toxicity

  20 weeks

• Type, incidence and severity of laboratory abnormalities

  20 weeks

Study Arms (2)

Arm A

ACTIVE COMPARATOR

6 cycles chemotherapy with Oxaliplatin 85 mg/m\^2 and Leucovorin 350 mg/m\^2 i.v. as 2h infusion on Day 1 and 5-FU 400 mg/m\^2 i.v. as bolus on Day 1 and 2400 mg/m\^2 as 46 h infusion q2w followed by surgery 4 weeks after last neoadjuvant chemotherapy treatment

Drug: Oxaliplatin; Drug: 5-FU; Drug: Leucovorin

Arm B

EXPERIMENTAL

6 cycles chemotherapy with Oxaliplatin 85 mg/m\^2 and Leucovorin 350 mg/m\^2 i.v. as 2h infusion on Day 1 and 5-FU 400 mg/m\^2 i.v. as bolus on Day 1 and 2400 mg/m\^2 as 46 h infusionq2w + Aflibercept 4 mg/kg BW i.v. on Day 1 q2w (6th cycle without Aflibercept) followed by surgery 4 weeks after last neoadjuvant chemotherapy treatment

Drug: Oxaliplatin; Drug: 5-FU; Drug: Leucovorin; Biological: Aflibercept

Interventions

Oxaliplatin DRUG

Oxaliplatin 85 mg/m\^2, as 2h infusion on Day 1 (Arm A + Arm B)

Arm A; Arm B

5-FU DRUG

5-FU 400 mg/m\^2 i.v. as bolus on Day 1 and 2400 mg/m\^2 as 46 h infusion q2w (Arm A + Arm B)

Arm A; Arm B

Leucovorin DRUG

Leucovorin 350 mg/m\^2 i.v. as 2h infusion on Day 1 (Arm A + Arm B)

Arm A; Arm B

Aflibercept BIOLOGICAL

Aflibercept 4 mg/kg BW i.v. on Day 1 q2w (Arm B, Cycles 1 to 5)

Arm B

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years on day of signing informed consent
• Signed and dated informed consent, and willing and able to comply with protocol requirements
• WHO/ECOG Performance Status (PS) 0-1
• Diagnosis of rectal adenocarcinoma
• Candidate for sphincter-sparing surgical resection prior to neoadjuvant therapy according to the primary surgeon, i.e. no patient will be included for whom surgeon indicates need for abdomino-perineal resection (APR) at baseline.
• Clinical staging is based on the combination of the following assessments:
• Physical examination by the primary surgeon
• CT scan of the chest/abdomen
• Pelvic MRI
• Rigid rectoscopy / endoscopic ultrasound (ERUS).
• Both examinations (i.e. MRI and ERUS) are mandatory.
• The tumor has to fulfill the following criteria:
• No symptomatic bowel obstruction
• Locally advanced rectal and rectosigmoid cancer, i.e. lower border of tumor \> 5 cm and \< 16 cm from anal verge as determined by rigid rectoscopy
• MRI criteria:

You may not qualify if:

• Distant metastases (CT scans of thorax and abdomen are mandatory)
• cT2 and cT4 tumors (defined by MRI criteria)
• Prior antineoplastic therapy for rectal cancer
• History or evidence upon physical examination of CNS metastasis
• Uncontrolled hypercalcemia
• Pre-existing permanent neuropathy (NCI-CTCAE grade ≥ 2)
• Uncontrolled hypertension (defined as systolic blood pressure \> 150 mmHg and/or diastolic blood pressure \> 100 mmHg), or history of hypertensive crisis, or hypertensive encephalopathy
• Concomitant protocol unplanned antitumor therapy (e.g. chemotherapy, molecular targeted therapy, immunotherapy, radiotherapy)
• Treatment with any other investigational medicinal product within 28 days prior to study entry
• Known dihydropyrimidine dehydrogenase (DPD) deficiency
• Treatment with CYP3A4 inducers unless discontinued \> 7 Days prior to randomization
• Grade 3-4 gastrointestinal bleeding
• Treatment resistant peptic ulcer disease
• Erosive esophagitis or gastritis
• Infectious or inflammatory bowel disease

Sponsors & Collaborators

• AIO-Studien-gGmbH: lead
• Institut für Klinisch-Onkologische Forschung (IKF) Frankfurt: collaborator
• Sanofi: collaborator

Study Sites (1)

Tagestherapiezentrum am ITM & III. Med. Klinik

Mannheim, 68167, Germany

Location

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Oxaliplatin; Fluorouracil; Leucovorin; aflibercept

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

Study Officials

• Ralf-Dieter Hofheinz, Prof. Dr.

  Tagestherapiezentrum am ITM & III. Med. Klinik, Universitätsmedizin Mannheim

  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: January 31, 2017
• First Posted: February 6, 2017
• Study Start: March 6, 2017
• Primary Completion: January 11, 2021
• Study Completion: June 1, 2022
• Last Updated: February 6, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)