A Multicenter, Open-Label, Randomized, Phase 2 Study to Evaluate the Efficacy and Safety of NKTR-102 Versus Irinotecan in Patients with Second-Line, Irinotecan-Naïve, KRAS-Mutant, Metastatic Colorectal Cancer (mCRC).
- Conditions
- Irinotecan-Naïve, KRAS-Mutant, Metastatic Colorectal cancer (mCRC)MedDRA version: 14.1Level: LLTClassification code 10065147Term: Malignant solid tumorSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 14.1Level: PTClassification code 10061451Term: Colorectal cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2008-004093-40-DE
- Lead Sponsor
- ektar Therapeutics
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 174
Each patient must meet the following criteria to be enrolled in this study:
1. Provide signed and dated informed consent prior to study-specific screening procedures.
2. = 18 years old.
3. Patients must have histological confirmation of colorectal adenocarcinoma. Patients must have metastatic disease with at least 1 uni-dimensionally measurable lesion meeting RECIST version 1.1 guidelines (see Section 12.1.1). Either computed tomography (CT) or magnetic resonance imaging (MRI) scanning is acceptable. Patients must have an
acceptable quality radiologic exam as assessed by Sponsor or Sponsor’s designee.
4. KRAS mutation determined from tumor tissue (primary tumor or metastasis). The presence of a KRAS mutation may be determined from patients’ original diagnostic block.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6. Patients must have received at least 1 but no more than 1 prior fluoropyrimidine containing regimen in the metastatic setting and must be naïve to irinotecan. Patients may also have received a fluoropyrimidine in the adjuvant or neoadjuvant setting.
7. Standard prior radiation therapy for rectal cancer is allowed. Patients must have recovered from the toxic effects of radiation prior to study enrollment. Prior radiotherapy must be completed 28 days before study entry.
Lesions that have been radiated in the advanced setting cannot be included as sites of measurable disease unless clear tumor progression has been documented in these lesions since the end of radiation therapy.
8. Adequate organ and bone marrow function at the Screening Visit defined as:
a. Absolute neutrophil count = 1,500/mm3 without myeloid growth factor support for 21 days preceding the lab assessment
b. White blood cell (WBC) count = 3,000/mm3 without myeloid growth factor support for 21 days preceding the lab assessment
c. Platelet count = 100,000/mm3, without transfusion within 7 days preceding the lab assessment
d. Hemoglobin = 9 g/dL, without transfusion support within 7 days preceding the lab assessment
e. Total bilirubin = 2 mg/dL
f. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) = 3 x ULN (= 5 x ULN if the presence of liver metastasis is confirmed)
g. Creatinine = 1.5 times ULN or creatinine clearance = 60 mL/min
9. Women of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test at Cycle 1 Day 1.
10. Women of childbearing potential, or men whose female partners are of childbearing potential, must agree to use at least 2 forms of contraception, 1 of which includes a barrier method (male condom) by the male partner, during the treatment period. Appropriate contraception must be used for at least 8 months after the last dose of the study drug.
11. Patients must be able and willing to comply with the study visit schedule and study procedures.
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 121
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 53
Patients who meet any of the following criteria will not be permitted entry to the study:
1. Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to Day 1 of Cycle 1, and have not, as deemed by the Investigator, recovered to NCI-CTCAE Grade 0 or 1 toxicity (any NCI-CTCAE grade of alopecia is allowed) associated with previous treatment irrespective of the
interval from the last treatment.
2. Patients who have had any major surgery within 4 weeks prior to Day 1 of Cycle 1 or minor surgery within 2 weeks of Day 1 of Cycle 1.
3. Administration of any of the following CYP3A4 inducer or inhibitor: phenytoin, phenobarbital, carbamazepine, rifampin, rifabutin, St. John’s Wort, ketoconazole, neuromuscular agents or atazanavir sulfate (Section 8.6.2) within 2 weeks prior to the first day of study drug treatment.
4. Patients who have received biologic agents including antibodies (e.g., bevacizumab, trastuzumab, etc.) as well as investigational agents within 28 days prior to the first day of study drug treatment.
5. Patients who have received any treatment with a camptothecin derivative (e.g., irinotecan, topotecan, SN-38 investigational agents, etc.).
6. Known or suspected central nervous system metastases.
7. Pregnant or lactating.
8. Other malignancy within the past 5 years except for any of the following: non-melanoma skin cancer, carcinoma in situ of the cervix, or any another malignancy with no evidence of recurrence for more than 5 years.
Patients with a history of low-grade (Gleason score less than or equal to 6) localized prostate cancer will be eligible even if diagnosed less than 5 years previously.
9. Liver cirrhosis.
10. Interstitial pneumonitis.
11. Any other significant co-morbid conditions that, in the judgment of the Investigator, would impair study participation or cooperation.
12. Patients with a history of hypersensitivity or intolerance to other PEGylated drugs or to the excipients of irinotecan/Camptosar.
13. Patients with inflammatory bowel disease (e.g., Crohn’s disease and ulcerative colitis), unresolved bowel issues (e.g., diverticulitis, ileitis, colitis, complete bowel obstruction etc.) or patients with chronic or acute gastrointestinal disorders with diarrhea as a major symptom.
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