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
- ocally advanced rectum cancerMedDRA version: 20.0Level: LLTClassification code 10007464Term: Carcinoma rectumSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-003064-38-PL
- Lead Sponsor
- Adlai Nortye USA INC.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- 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 of a major thromboembolic event
7.Subjects receiving oral warfarin are not eligible for this study (unless warfarin is discontinued at least 7 days prior to commencement of treatment and for the duration of the study, or oral warfarin is converted to low molecular weight heparin, where local clinical opinion considers this an acceptable option).
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 [ßhCG]
test with a minimum sensitivity of 25 IU/L or equivalent units of ßhCG). A separate baseline assessment is required if a negative
screening pregnancy test was obtained more than 72 hours before the
first dose of study
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