Study of Mycobacterium in Adjuvant Setting in Advanced Stage of Lung Cancer.

Phase 4

Not yet recruiting

Conditions: Malignant neoplasm of lower respiratory tract, part unspecified,

Registration Number: CTRI/2020/09/027853

Lead Sponsor: Tata Memorial Hospital

Brief Summary: **STUDY DESIGN:**

The present study is an open label, randomized, clinical trial to assess safety and efficacy between test arm and control arm in Stage-IIIb/IV NSCLC patients. After obtaining the informed consent, patients meeting inclusion and exclusion criteria, will be randomized to test and control arm in 1:1 ratio, respectively. The total sample size required for the present study is 834.

**Stratification in randomization will done based on histology and PS of treatment.**

Patients will receive chemotherapy by intravenous infusion on day 1 of a 21 days cycle for 4 chemotherapy cycles as a part of their standard therapy. In same test arm, first dose of *Mw* (test arm) or will be administrated 7 days prior to 1st chemotherapy cycle followed by their administration into respective arms on 8th and 15th days of all four chemotherapy cycles. After completion of chemotherapy, patients will receive one dose of *Mw* (test arm) or every month till 12 months from the start of the chemotherapy or patientâ€™s death, whichever is earlier.

During chemotherapy and after chemotherapy cycle, patients will be followed up physically or telephonically at every visit up to one month after last dose of *Mw* (test arm) or its for safety. Safety laboratory parameters will be performed at siteâ€™s laboratory. CT scan will be performed at baseline, 2 months, 4 month, 8 month and 12 month of *Mycobacterium w* (*Mw*) treatment to determine tumor response rate.

Efficacy parameters will include Overall survival in all randomized patients.

Patients will visit the investigator site at regular intervals as specified in the flow chart (section 5.0) for trial related visit specific activities. Patientâ€™s study participation duration in the study will be up to one month after last dose of *Mw* (test arm) arm) or death whichever is earlier.

TREATMENT REGIMENBoth arms will receive and platinum based chemotherapy by intravenous infusion on day 1 of a 21 days cycle for 4 chemotherapy cycles.In addition in test arm, first dose of *Mw* will be administrated 7 days prior to 1st chemotherapy cycle followed by their administration on 8th and 15th days of all four chemotherapy cycles. After completion of chemotherapy, patients will receive one dose of *Mw* every month till 12 month from the start of the chemotherapy or patientâ€™s death, whichever is earlier.For squamous carcinoma- paclitaxel 175 mg/m2 with carboplatin AUC-5 backbone will be used for 4 cycles delivered 21 days apart. While for adenocarcinoma pemetrexed 500 mg/m2 with carboplatin AUC-5 backbone will be used for 4 cycles delivered 21 days apart. After which pemetrexed maintainnenece will continue every 3 weekly till progression.

**STATISTICAL ANALYSIS PLAN**

The material in this section forms the basis for the statistical analysis plan for the study. This plan may be revised during the study to accommodate clinical trial protocol amendments and to make changes to adapt to unexpected issues in study execution and data that affect planned analysis. These revisions will be based on blinded review of the study and data, and a final plan will be issued before database lock.

**SAMPLE SIZE DETERMINATION**

The study would have 2 types of patient- Squamous cell and Non-squamous. Both of these groups are independently powered for analysis. The sample size for each group is as per below.

For adenocarcinoma assuming a 1 year OS of 49.0% ( Gandhi et al), with the expected improvement of 10%, with type 1 error of 5% (1-sided), Type 2 error of 20%, with a study duration of 5 years and estimated lost to follow up of 10%, we required 404 patients with event for analysis being 272.

For squamous cell carcinoma assuming a 1 year OS of 40.0% (Patil et al), with the

expected improvement of 10%, with type 1 error of 5% (1-sided), Type 2 error of 20%,

with a study duration of 5 years and estimated lost to follow up of 10%, we required 430 patients with event for analysis being 317.

The combined analysis will have the strength to detect an improvement in HR-0.81, assuming a1 year OS of 45% and the rest parameters being similar to subgroup analysis.

Detailed Description: Not available

Recruitment & Eligibility

Status: Not Yet Recruiting

Sex: All

Target Recruitment: 834

Inclusion Criteria

1 Patients willing to comply with the protocol and have signed IEC or IRB approved informed consent form (ICF).
2 Histologically confirmed Stage IIIb/IV NSCLC patients (as per AJCC Classification) without any driver mutation planned with treatment with palliativecare 3 Eligible for cytotoxic combination chemotherapy as a first linetherapy 4 Male or female patient aged 18-years or more; Eastern Cooperative Oncology Group (ECOG) performance status of 0-2; and Life Expectancy of at least 24weeks 5 Adequate organ function as evidenced by hematological and biochemical tests.
6 Negative pregnancy test for women of child bearing potential prior to entry into the trial.
Women of childbearing potential or men with partners of childbearing potential must use effective physical contraceptive measures during treatment and at least 6 months after the last dose of the study treatment.
If a woman becomes pregnant or suspects she is pregnant while participating in this study, she must agree to inform her treating physician immediately.

Exclusion Criteria

1 Patients with untreated symptomatic brain metastasis.
Patients with symptomatic brain mets after receiving RT to brain can be included in the study 2 Malignancy other than NSCLC within 5 years prior to enrollment, with the exception of basal cell carcinoma or carcinoma insitu of the cervix.
3 History of allergic reactions attributed to paclitaxel, platinum based chemotherapy or mycobacteria or any of their ingredients 4 Pregnant women or nursingwomen 5 Uncontrolled inter- current illness that would limit compliance with study requirements 6 HIV positive patients with CD4 count less than 200 7 Previous splenectomy 8 A major surgical procedure, or significant traumatic injury â‰¤28 days of beginning treatment, or anticipation of the need for major surgery during the course of thestudy 9 Current, recent, or planned participation in another experimental drug study 10 Patients who had cytotoxic chemotherapy and/or radiotherapy (except palliative radiotherapy within 2 weeks prior to enrollment).

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Overall Survival	Randomization till death

Secondary Outcome Measures

Name	Time	Method
1 To compare safety	2 To assess Tumour responserate

Trial Locations

Locations (1): Tata Memorial Hospital
🇮🇳
Mumbai, MAHARASHTRA, India
Tata Memorial Hospital
🇮🇳Mumbai, MAHARASHTRA, India
Dr Kumar Prabhash
Principal investigator
09167760576
kprabhash1@gmail.com