Induction FOLFOX With or Without Aflibercept Followed by Chemoradiation in High Risk Locally Advanced Rectal Cancer

• Status: Completed
• Trial end date: 2020-02-04
• Target enrollment: 0
• Participant gender: All

Summary

This trial compares induction treatment with FOLFOX with or without aflibercept in a high risk population selected by MRI, prior to receiving standard chemoradiation (capecitabine combined with 50.4 Gy in 28 days) and surgery, in order to evaluate the efficacy in terms of pathologic complete response (pCR).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Grupo Espanol Multidisciplinario del Cancer Digestivo
• Collaborator: Pivotal S.L.
• Treatments: Aflibercept; Fluorouracil; Leucovorin; Oxaliplatin

Criteria

Inclusion Criteria:

1. Signed and dated informed consent, and willing and able to comply with protocol requirement;

2. Male or female subjects with rectal cancer ≥18 and <70 years of age;

3. High risk MRI-defined operable rectal cancer (with an inferior margin no more than 12 cm above the anal verge as assessed by MRI). Presence of at least 1 of the following on high resolution, thin-slice MRI (3 mm):

Middle Third Tumors

• mr T3

1. Extramural vascular invasion (EMVI) positive

2. Extramural extension > 5 mms into perirectal fat

3. Mesorectal fascia (MRF) threatened or involved*

• mr T4***

Distal Third Tumors (≤5 cm from anal verge)

• mr T3 tumor at or below levators

• T4 as above N2**

• tumor or lymph node < 1 mm from the mesorectal fascia **≥4 lymph nodes in the mesorectum showing morphological signs on MRI indicating metastatic disease. ≥4 nodes, whether enlarged or not, with a rounded, homogeneous appearance is thus not sufficient.

• T4a: overgrowth to an adjacent organ or structure or T4b: peritoneal involvement.

4. Histologically confirmed adenocarcinoma of the rectum. All other histological types are excluded;

5. Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤1;

6. Hematological status: neutrophils (ANC) ≥1.5x109/L; platelets ≥100x109/L; hemoglobin ≥9g/dL;

7. Adequate renal function: serum creatinine level <1.5 x upper limit of normality (ULN);

8. Adequate liver function: serum bilirubin ≤1.5 x ULN, alkaline phosphatase <5x ULN, AST/ALT < 3 x ULN;

9. Proteinuria <2+ (dipstick urinalysis) or ≤1g/24hour;

10. Regular follow-up feasible;

11. For female patients of childbearing potential, negative serum pregnancy test within 1 week (7 days) prior to starting study treatment;

12. Female patients must commit to using reliable and appropriate methods of contraception until at least three months after the end of study treatment (when applicable). Male patients with a partner of childbearing potential must agree to use contraception in addition to having their partner use another contraceptive method during the trial.

Exclusion Criteria:

1. Prior treatment with aflibercept;

2. History or evidence upon physical examination of metastasis;

3. Uncontrolled hypercalcemia;

4. Pre-existing permanent neuropathy (NCI grade ≥2);

5. Uncontrolled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 mmHg), or history of hypertensive crisis, or hypertensive encephalopathy;

6. Concomitant protocol unplanned antitumor therapy (e.g. chemotherapy, molecular targeted therapy, immunotherapy);

7. Treatment with any other investigational medicinal product within 28 days prior to study entry;

8. Other concomitant or previous malignancy, except: i/ adequately treated in-situ carcinoma of the uterine cervix, ii/ basal or squamous cell carcinoma of the skin, iii/ cancer in complete remission for >5 years;

9. Any other serious and uncontrolled non-malignant disease, major surgery or traumatic injury within the last 28 days;

10. Pregnant or breastfeeding women;

11. Patients with known allergy to any excipient to study drugs;

12. History of myocardial infarction and/or stroke within 6 months prior to randomization; Previous history of stable angina, uncontrolled arrhythmia, and acute coronary syndrome even if controlled with medication or with myocardial infarction within the last 12 months.

13. Bowel obstruction.