A Randomized, Multi-Center, Open-Label, Phase II Study to Evaluate the Efficacy and Safety of Recombinant Super-Compound Interferon (rSIFN-co) in Combination With Total Neo-adjuvant Therapy, in Subjects With Mid-low Locally Advanced Rectal Cancer
A Randomized, Multi-Center, Open-Label, Phase II Study to Evaluate the Efficacy and Safety of Recombinant Super-Compound Interferon (rSIFN-co) in Combination With Total Neo-adjuvant Therapy, in Subjects With Mid-low Locally Advanced Rectal Cancer
This is a multi-center, randomized, phase II study, aimed to evaluate the efficacy of investigational product at a dose of 1800 µg/day when given in combination with TNT. There will be two arms included in this study: Arm A (TNT regimen
+ 1800 µg/day of rSIFN-co treatment) and Arm B (TNT regimen only). Subjects will be randomly assigned to any of the two arms in a 2:1 ratio to receive TNT regimen concurrently with rSIFN-co treatment twice a week or TNT regimen only. The efficacy of rSIFN-co when given in combination with Total Neo-adjuvant Therapy (TNT) will be measured by complete response. Where, complete response is defined as subjects with pathological complete response (pCR) or clinical complete response (cCR).
Inclusion Criteria:
1.Male and female subjects ≥18 years of age and having BMI ≥ 17 kg/m2. 2.Subjects with histologically or cytologically confirmed mid-low locally advanced rectal cancer, with tumor location within 12 cm from the anal verge, as per UICC classification, and who are scheduled to undergo TNT in the opinion of the investigator 3.Subjects having rectal cancer with pMMR/MSS tumor type and TNM stage: T3, N any, M0; T1-2, N1-2, M0; T4, N any, M0 or locally unresectable or medically inoperable or subjects who are eligible for sphincter sparing surgery.
4.Subjects with ECOG Performance Status 0-2 (Ambulatory and capable of all self-care but unable to carry out any work activities; up and about more than 50% of waking hours). [As per Appendix A] 5.Subjects with life expectancy of at least 6 months 6.Subjects willing and able to comply with all study requirements, including study treatment, timing and/or nature of required assessments.
7.Subjects with normal organ functions prior to enrollment in study:
Blood routine examination
* WBC: ≥ 4×109/L;
Biochemical examination * Total bilirubin (TBIL) ≤ 1.5 × ULN;
ALT and AST ≤ 2.5 × ULN; Creatinine clearance (CrCl) ≥ 60ml/min using the Cockcroft Gault formula 8.Adequate coagulation function, defined as international normalized ratio (INR) and prothrombin time (PT) ≤ 1.5 × ULN; 9.Female subjects with negative serum pregnancy test at screening and negative urine pregnancy test at baseline.
10.Female subjects of childbearing potential agrees to use a medically acceptable method of contraception throughout the study and for at least 6 months after receiving the final dose.
Acceptable methods of contraception are:
Intrauterine device (IUD) or Intrauterine system (IUS)
Double barrier method of contraception (condom and occlusive cap or condom and spermicidal agent)
Male sterilization (at least 06 months prior to the screening, should be the sole male partner for that subject)
Female sterilization (surgical bilateral oophorectomy) or tubal ligation at least 06 weeks prior to study participation
Total abstinence (partial abstinence is not acceptable). 11.Male subjects with female partners of reproductive potential must agree to use condoms (or any barrier method of contraception) throughout the study and for at least 3 months after receiving the final dose.
Exclusion Criteria:
1.Subjects with known hypersensitivity or contraindication to study drug or to any known component of study drug formulation.
2.Subjects who have received treatment with interferon and interferon-like therapy within 30 days prior to screening.
3.Subjects who had present or prior malignancy other than study indication (except cured basal or squamous cell carcinoma, cervical carcinoma).
4.Subjects who have received radiotherapy prior to screening or had a history of radiotherapy around the pelvic area.
5.Subjects with known or confirmed severe gastrointestinal inflammation, ileus, or chronic diarrhea (>3 loose stools per day).
6.Subjects with known or confirmed distant tumor metastasis. 7.Subjects with rectal obstruction and significant bleeding. 8.Subjects with history of surgery or trauma: major surgery within 8 weeks prior to screening, such as laparotomy, thoracotomy, organ resection, etc (excluding diagnostic surgical procedures); severe, non-healing wounds, ulcers, or fractures within 8 weeks prior to screening; minor surgery within 7 days prior to screening (excluding diagnostic surgical procedures).
9.Subjects with other serious conditions that may restrict their participation in the trial (e.g., progressive infection, uncontrolled diabetes or uncontrolled hypertension, serious cardiac dysfunction or angina, active autoimmune disease, etc.).
10.Subjects with active infection as determined by positive serology for Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), or Human Immunodeficiency Virus (HIV).
Note: Subjects with controlled HIV, HBV, or HCV infection by antiretroviral therapy will not be excluded.
11.Subjects with other uncontrolled active infections (Grade CTCAE V5.0 >2), who require treatment with IV antimicrobial therapy, and subjects with active tuberculosis, and subjects undergoing anti syphilis treatment.
12.Subjects with a history of severe skin disease. 13.Subjects with known or confirmed presence of other uncontrollable benign diseases of the lung, liver or kidney and known or confirmed presence of any infection.
14.Subjects with any other medical condition or serious inter-current illness that, in the opinion of the Investigator, may make it undesirable for the subject to participate in the study including but not limited to cirrhosis or psychiatric illness/social situations that would limit adherence to study requirements.
15.Pregnant or lactating women, or female subjects unwilling to use any form of contraception during the study.
16.Subjects with history of alcohol or drug abuse.