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Adaptive ctDNA-Based Personalization of Treatment During Consolidation Therapy in NSCLC

ConditionsNon Small Cell Lung CancerNSCLC, Stage IIINsclc
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorStanford University

About this trial

The purpose of this study is to test whether or not number of circulating cancer cells detected in the blood can be decreased the by combining the standard treatment (durvalumab) with Tremelimumab and additional chemotherapy

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Histologically- or cytologically-documented NSCLC presenting with locally-advanced, unresectable stage III disease (Version 8 of AJCC Staging Manual) or NSCLC with locoregional recurrence after previous definitive treatment.

For stage III or recurrent disease, must have completed platinum-based chemotherapy and radiation therapy to all known tumor sites (60 Gy +/- 10%). Must not have known progression of disease.

Must be receiving consolidation durvalumab following completion of radiation and chemotherapy, and less than 32 weeks has elapsed from their first dose of durvalumab. (Patients may sign consent for study before start of durvalumab, but confirm eligibility and enroll only after first dose of durvalumab is received).

Able to potentially receive further consolidation chemotherapy plus durvalumab and tremelimumab, but not be currently intended to receive additional systemic consolidation chemotherapy apart from this durvalumab.

Disqualifiers

Subjects with Grade ≥ 2 neuropathy will be evaluated on a case by case basis after consultation with the Protocol Director / Principal Investigator

Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by treatment with durvalumab may be included (ie, hearing loss) only after consultation with the Protocol Director / Principal Investigator.

Vitiligo or alopecia

Hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement

Trial design

Design model

Parallel

Treatments tested in this trial

  • Durvalumab

    Drug

    Cohort 1 (1500 mg IV every 21 days, for 1 year), •Cohort 2 (10mg/kg every 2 weeks for 1 year)

  • Carboplatin

    Drug

    Target area under the curve (AUC) not to exceed 750mg on Day 1 of every 21-day cycle

  • Pemetrexed

    Drug

    500mg/m2 on Day 1 of every 21-day cycle

  • Paclitaxel

    Drug

    175mg/m2 on Day 1 of every 21-day cycle

  • Cisplatin

    Drug

    Cisplatin (75mg/m2 per institution guidelines) may be substituted for Carboplatin

  • AVENIO ctDNA Surveillance Kit

    Device

    Roche Sequencing and Life Science kit to detect minimal residue disease (MRD)

  • Tremelimumab

    Drug

    not to exceed 75mg IV on Day 1 of every 21-day cycle

Treatment groups

48 Participants
are divided into 2 treatment groups
Group A: Cohort 1 minimal residual disease positive (MRD+)Experimental treatment 7 interventions
Group B: Cohort 2 minimal residual disease negative (MRD )Experimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

Change in ctDNA Level Following Chemotherapy

Participants in Cohort 1 MRD+ will be assessed for ctDNA levels at baseline and end of treatment, expected to be 4 cycles of 3 weeks per cycle (defined as ctDNA evaluable set or ctDES). The outcome will be assessed as the number of participants with a ≥ 3 fold decrease in ctDNA level, a number without dispersion.

Time frame
12 weeks

Secondary outcomes

1

Presence of Detectable ctDNA Following Chemotherapy

Participants in Cohort 1 MRD+ will be assessed for ctDNA levels at baseline and end of treatment, expected to be 4 cycles of 3 weeks per cycle. The outcome will be assessed as the number of participants with or without detectable ctDNA, a number without dispersion.

Time frame
12 weeks
2

Overall Survival (OS)

Overall survival (OS) is defined as the period a participant remains alive after study registration until death due to any cause. Participants lost to follow up will be censored at last known date alive. The outcome will be reported as the number of participants in both cohorts remaining alive after 2 years, a number without dispersion.

Time frame
2 years
3

Progression free survival (PFS)

Progression free survival (PFS) is defined as the period a participant remains alive without disease progression after study registration. Tumor status is assessed per the Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1) by computed tomography (CT), positron emission tomography (PET) CT; and/or X rays. Participants lost to follow up will be censored at last known date alive. The outcome will be reported as the number of participants in both cohorts remaining alive without progression after 2 years, a number without dispersion. * Complete Response (CR) = Disappearance of all lesions * Partial Response (PR) = ≥30% decrease in the sum of the lesion diameters * Overall Response (OR) = CR + PR * Progressive disease (PD) = 20% increase in the sum of lesion diameters, and/or the appearance of 1+ new lesion(s) * Stable disease (SD) = Small changes that do not meet any of the above criteria

Time frame
2 years
4

Durvalumab and Tremelimumab related Adverse Events (Cohort 1 MRD+ only)

Adverse events will be collected for participants of Cohort 1 (MRD+) who initiate treatment with durvalumab and tremelimumab through 930 days after the last dose of durvalumab. AE grade per the Common Terminology Criteria for Adverse Events (CTCAE v5) criteria and relationship to study treatment will be assessed. The outcome will be reported as the number of durvalumab and tremelimumab related adverse events by grade that Cohort 1 MRD+ participants experienced.

Time frame
13 months

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Stanford University

Lead sponsor

AstraZeneca

Collaborator

Source ClinicalTrials.gov
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