A trial to investigate the safety and tolerability of E7046 when it is given together with radiation and chemotherapy before surgery in patients who have rectum cancer.
- Conditions
- locally advanced rectum cancerMedDRA version: 20.0 Level: LLT Classification code 10007464 Term: Carcinoma rectum System Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-003064-38-GB
- Lead Sponsor
- Adlai Nortye USA Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 35
1.Diagnosis of histologically confirmed invasive primary rectal carcinoma
2.Age =18 years at the time of informed consent
3.Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
4.Subjects must have locally advanced rectum cancer where primary resection without CRT is unlikely to achieve clear margins as defined by MRI, with no metastatic disease, as assessed by local review.
5.Disease which can be encompassed within a radical radiotherapy treatment volume
6.Subject must consent to repeated biopsy as detailed in Table 5 (Section 9.4.2.1) to allow the acquisition of fresh and/or formalin-fixed paraffin-embedded (FFPE) material. Available archived tumor material may be submitted as the pretreatment biopsy provided that minimum requirements are met by local pathology review as defined in the laboratory manual. If archived tumor material is not available or does not meet minimum requirements then a fresh tumor biopsy must be obtained in accordance with local institutional practice.
7.Adequate renal function defined as serum creatinine <1.5 × upper limit of normal (ULN) (or use SI units or calculated creatinine clearance =50 mL/min per the Cockcroft and Gault formula [Appendix 1]).
8.Adequate bone marrow function:
a.Absolute neutrophil count (ANC) = 1500/mm3 (= 1.5 × 103/µL)
b.Platelets = 100,000/mm3 (= 100 × 109/L)
c.Hemoglobin = 9.0 g/dL
9.Adequate liver function:
a.Adequate blood coagulation function as evidenced by an International Normalized Ratio (INR) = 1.5.
b.Total bilirubin = 1.5 × ULN except for unconjugated hyperbilirubinemia or Gilbert’s syndrome.
c.Alkaline phosphatase, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) = 2.5 × ULN.
10.No prior pelvic radiotherapy, chemotherapy, immunotherapy or other anti-cancer treatment for rectal cancer
11.No prior exposure to CSF1R antagonists such as but not limited to emactuzumab (RG7155) (Roche), PLX3397 (Plexicon), JNJ40346627 (J & J), including both anti-CSF1R and small molecule inhibitors and EP4 antagonists.
12.No preexisting condition which would deter radiotherapy, eg, fistulas, severe ulcerative colitis (particularly subjects currently taking sulphasalazine), Crohn’s disease, prior adhesions.
13.Willing and able to give informed consent and comply with all aspects of the protocol.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 23
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 12
1.Any contraindications to MRI.
2.Unfit to receive study treatment or subsequent surgical resection.
3.Active hydronephrosis.
4.Unequivocal evidence of metastatic disease defined by CT (includes resectable metastases).
5.Prolongation of corrected QT (QTc) interval to >480 msec when electrolyte balance is normal.
6.Recent occurrence (within 3-6 months) of a major thromboembolic event.
7.Subjects receiving oral warfarin are not eligible for this study.
8.Previous radiotherapy in the pelvic region.
9.Cardiac conditions.
10.Has a known additional malignancy that is progressing and/or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy, previous ductal carcinoma in situ (DCIS), or breast cancer diagnosed more than 5 years ago, as long as adequately treated or in situ, or early (up to stage 1B1) cervical cancer, or vulval intraepithelial neoplasia (VIN), or vulval cancer adequately treated without pelvic RT
11.Refractory nausea and vomiting, chronic gastrointestinal diseases (eg, inflammatory bowel disease), or significant bowel resection that may impair adequate absorption and bioavailability of study drug. Major disturbance of bowel function (eg, gross fecal incontinence or requiring > 6 mg loperamide each day).
12.Subjects with prior Hepatitis B or C infection with inadequate liver function (adequate liver function as defined in inclusion Criterion # 9)
13.Recent major surgery within 4 weeks prior to entry into the study (excluding the placement of vascular access and defunctioning stoma or any other surgical procedures not considered major by the investigator) which would prevent administration of study treatment.
14.Known dihydropyrimidine dehydrogenase (DPD) deficiency.
15.Subjects with progressive neurological dysfunction that would confound the evaluation of neurological and other toxicities; any evidence of severe or uncontrolled systemic disease, active infection, active bleeding diatheses or renal transplant, including any subject with known active hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infection.
16.Subjects with interstitial pneumonia or extensive and symptomatic fibrosis of the lungs
17.Subjects with any active autoimmune disease or a documented history of autoimmune disease, poorly controlled asthma or history of syndrome that required systemic steroids or immunosuppressive medications, except for subjects with vitiligo or resolved childhood asthma/atopy. Subjects with asthma who require intermittent use of bronchodilators (such as albuterol) will not be excluded from this study.
18.Any other major illness that, in the investigator’s judgment, will substantially increase the risk associated with the subject’s participation in this study
19.Has received a live vaccine within 30 days of planned start of study therapy.
20.Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a negative beta-human chorionic gonadotropin [ß-hCG] test with a minimum sensitivity of 25 IU/L or equivalent units of ß-hCG). A separate baseline
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method