Clinical trial NCT05856305: SCRT in TNT With or Without Chlorophyllin
Official title: Phase II Randomized Study of Short Course Radiotherapy Based Total Neoadjuvant Therapy & Brachytherapy Boost With Or Without Chlorophyllin In Watch And Wait Suitable Locally Advanced Rectal Cancer (SCOTCH Study)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Rectal Neoplasms
Keywords: Locally Advanced rectal cancer
Sodium Copper Chlorophyllin
Lead sponsor: Tata Memorial Centre
Sponsor class: OTHER
First posted: 2023-05-12
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to see, if addition of chlorophyllin to neoadjuvant Chemo-radiotherapy can reduce the gastro-intestinal/genitourinary/hematological toxicity rates and improve the quality of life in patient's diagnosed with locally advanced rectal cancer.

This is a randomized placebo control trial, wherein participants randomized to Chlorophyllin arm will receive the drug of interest along with the standard treatment. Participants randomized to other arm will receive placebo along with the standard treatment.

Researchers will compare the difference between the outcomes from both the arms and will also observe the non-operative management success rates.

Detailed description: The current standard treatment for locally advanced rectal cancer includes neoadjuvant (treatment given before Surgery) radiotherapy \& chemotherapy followed by surgery if needed or wait and watch in patients whom tumour has completely regressed. It has been observed that even after receiving this intensive treatment patients, almost 70% of patients develop acute toxicity (during or within 3 months) of grade 2 or higher (needing medication for toxicity). This affects their treatment tolerance, completion and quality of life.

In this study Researchers are going to see if addition of drug Chlorophyllin (derived from green plant leaves) along with standard treatment would help in reducing the acute toxicity. Chlorophyllin is present in all green leaves of plants giving them green color. The drug is derived from green plant leaves. As it is a plant-based product it is safe for humans and has no known side effects of its own. This is a randomized study which has two arms; Arm 1 is test arm where participants will receive drug of interest (Chlorophyllin) and in other arm participants will receive Placebo. Upon successful completion of study, outcomes from both the study arm will be compared and participants will be followed by standard protocol for 3 years.

Eligibility criteria: Inclusion Criteria:

* Age \> 18 years.
* Histologically confirmed diagnosis of adenocarcinoma of the rectum.
* Clinical Stage II/III (T2-3, 4b: adherent to prostate, SV or post vagina but not grossly invading, N0-2) based on MRI.
* Non-circumferential tumours with craniocaudal length \<7 cm
* The tumours of the lower rectum, or starting up to 7 cm from the anal verge.
* No evidence of distant metastases on CT Chest and Abdomen.
* No prior pelvic radiation therapy
* No prior chemotherapy or surgery for rectal cancer
* Eastern Cooperative Oncology Group (ECOG) Performance status 0-2
* Patients must read, agree to, and sign a statement of Informed Consent prior to participation in this study.
* Eligible to receive one of the options of standard neoadjuvant chemotherapy as determined by the medical oncologist team.

  * Absolute neutrophil count (ANC) \> 1.5 cells/mm3, hemoglobin (HGB) \> 8.0 gm/dl, platelet (PLT) \> 150,000/mm3.
  * Total bilirubin ≤ 1.5 x ULN (except in patients with Gilbert's Syndrome who must have total bilirubin ≤ 3.0 x ULN), aspartate aminotransferase (AST) ≤ 3 x ULN, alanine transaminase (ALT) ≤ 3 x ULN.

Exclusion Criteria:

* Signet or mucinous histology cancer of rectum
* Recurrent rectal cancer or previous pelvic radiotherapy
* Primary unresectable rectal cancer.
* Creatinine level greater than 1.5 times the upper limit of normal.
* Patients who are unable to undergo an MRI.
* Patients with a history of any arterial thrombotic event within the past 6 months. This includes angina (stable or unstable), MI, TIA, or CVA.
* Ulcerative colitis or any other histologically confirmed inflammatory bowel disease.
* Patients with a history of venous thrombotic episodes such as deep venous thrombosis, and pulmonary embolism occurring more than 6 months prior to enrollment may be considered for protocol participation, provided they are on stable doses of anticoagulant therapy. Similarly, patients who are anticoagulated for a trial fibrillation or other conditions may participate, provided they are on stable doses of anticoagulant therapy.
* Patients with any other concurrent medical or psychiatric condition or disease which, in the investigator's judgment, would make them inappropriate candidates for entry into this study.
* Poor reliability for follow up.
* Ineligible as per eligibility criteria

Primary outcomes:
measure: Acute Toxicity
timeFrame: 3 months post-last cytotoxic therapy.
Secondary outcomes:
measure: Overall successful complete response rates
timeFrame: 3 years
measure: Organ preservation rates
timeFrame: 3 years
measure: Disease free survival
timeFrame: 3 years
measure: Treatment related early and late toxicities
timeFrame: 2 years
measure: Estimation of surgical complications
timeFrame: 30 days post surgery
measure: Health related quality of life
timeFrame: 2 years
measure: Cost benefit with reduction in toxicity
timeFrame: 2 years
measure: Tumor Volume reduction kinetics
timeFrame: 2 years
measure: To evaluate the timeline of Occurence
timeFrame: 3 years
Other outcomes:
Locations:
city: Mumbai
country: India
facility: Tata Memorial Hospital
state: Maharashtra
Study officials:
affiliation: Tata Memorial Hospital
name: Prof. Rahul Krishnatry, M.D.
role: PRINCIPAL_INVESTIGATOR
References: