Metastatic colorectal carcinoma (mCRC) refractory to fluoropyrimidine-, irinotecan-, oxaliplatin- (if KRAS mutated) and panitumumab- or cetuximab- (if KRAS wild type) containing regimens MedDRA version: 14.1 Level: LLT Classification code 10052362 Term: Metastatic colorectal cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: DETICENE
Pharmaceutical Form: Powder and solvent for solution for infusion
INN or Proposed INN: NA
CAS Number: NA
Current Sponsor code: NA
Other descriptive name: NA
Concentration unit: mg
Sponsors
AZIENDA OSPEDALIERA OSPEDALE NIGUARDA CA' GRANDA (A.O. DI RILIEVO NAZIONALE)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Male or female = 18 years of age; 2. Eastern Cooperative Oncology Group (ECOG) performance status of = 1; 3. Life expectancy of at least 3 months; 4. Understand and voluntarily sign an informed consent form; 5. Histologically or cytologically confirmed metastatic colorectal adenocarcinoma; 6. Measurable disease (RECIST criteria v1.1) using conventional techniques (CT scan or MRI); 7. Previous treatment including: fluoropyrimidine, oxaliplatin, irinotecan for patients with mutant KRAS (as assessed in primary tumor or metastases evaluating codon 12 and 13 mutations) or fluoropyrimidine, oxaliplatin, irinotecan, cetuximab and/or panitumumab for patients with wild-type KRAS. 8. Imaging confirmed (CT/MRI) disease progression within 3 months of previous standard treatment. Patients who have been withdrawn from standard treatment due to unacceptable toxicity will also be allowed into the study. Patients treated with oxaliplatin in an adjuvant setting should have progressed during or within 6 months of completion of adjuvant therapy; 9. Women of childbearing potential and men must agree to use adequate contraception since signing of the informed consent form until at least 3 months after the last study drug administration; 5 10. Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment: · Total bilirubin 100000 /mm3, Hemoglobin (Hb) >9 g/dL, Absolute Neutrophil Count (ANC) >1500/mm3; · Alkaline phosphatase limit =65 years) yes F.1.3.1 Number of subjects for this age range 28
Exclusion criteria
Exclusion criteria: Prior treatment with dacarbazine or temozolomide; 2. Previous or concurrent cancer that is distinct in primary site or histology from colorectal cancer within 5 years prior to randomization EXCEPT for curatively treated cervical cancer in situ, non-melanoma skin cancer and superficial bladder tumors [Ta (Non-invasive tumor),Tis (Carcinoma in situ) and T1 (Tumor invades lamina propria)]; 3. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before start of study medication; 4. Pregnant or breast-feeding patients. Women of childbearing potential must have a pregnancy test performed a maximum of 7 days before start of treatment, and a negative result must be documented before start of treatment; 5. Congestive heart failure > New York Heart Association (NYHA) class 2; 6 6. Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months). Myocardial infarction less than 6 months before start of study medication. 7. Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), or pulmonary embolism within the 6 months before start of study medication; 8. Ongoing infection > grade 2 NCI-CTC version 3.0; 9. Untreated, symptomatic brain metastases (brain radiologic imaging not required); 10. Non-healing wound, ulcer, or bone fracture; 11. Renal failure requiring hemo-or peritoneal dialysis; 12. Substance abuse, medical, psychological or social conditions that may interfere with the patient’s participation in the study or evaluation of the study results; 13. Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation. Investigational Product Dosage and
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: This trial aims to assess activity dacarbazine in terms of objective response rate (ORR) in patients with mCRC refractory to standard therapies.;Secondary Objective: Evaluation of clinical benefit (disease control rate) 2. Evaluation of progression-free survival (PFS) 3. Identification of biomarkers of response to dacarbazine based on molecular characteristics of individual tumor samples: · loss of expression of O6-methylguanine-DNA-methyltransferase (MGMT) as evaluated by immunohistochemistry (IHC) and promoter hypermethylation; · KRAS status (wild type vs mutated) · population of mCRC with BRAF mutation will be also evaluated separately;Primary end point(s): ORR by RECIST criteria;Timepoint(s) of evaluation of this end point: eighteen weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: eighteen weeks more six months;Secondary end point(s): Disease control rate (ORR + Stable Disease by RECIST criteria) · PFS · Association of response/resistance with loss of expression of O6-methylguanine- DNA-methyltransferase (MGMT) and KRAS or BRAF mutations | — |
Countries
Italy
Contacts
Public ContactONCOLOGIA
ONCOLOGIA
Outcome results
None listed