Description:
The current study focuses on unresectable stage III non-small cell lung cancer (NSCLC)
patients who have disease progression while on Durvalumab consolidation after concurrent
chemoradiation with a goal of cure. The overall hypothesis of this study is that the addition
of Copanlisib to Durvalumab will be well-tolerated at a biweekly schedule. It will test
whether the addition of Copanlisib to Durvalumab can overcome resistance to Durvalumab.
Title
- Brief Title: Lung Cancer With Copanlisib and Durvalumab
- Official Title: Restoring Immune Response With Copanlisib in Locally Advanced Unresectable Non-Small Cell Lung Cancer on Durvalumab Failure, A Phase Ib Study
Clinical Trial IDs
- ORG STUDY ID:
MCC-20-LUN-119-PMC
- NCT ID:
NCT04895579
Conditions
- Non Small Cell Lung Cancer
Interventions
| Drug | Synonyms | Arms |
|---|
| Durvalumab | Imfinzi | Copanlisib (30mg flat dose) |
| Copanlisib | Aliqopa | Copanlisib (30mg flat dose) |
Purpose
The current study focuses on unresectable stage III non-small cell lung cancer (NSCLC)
patients who have disease progression while on Durvalumab consolidation after concurrent
chemoradiation with a goal of cure. The overall hypothesis of this study is that the addition
of Copanlisib to Durvalumab will be well-tolerated at a biweekly schedule. It will test
whether the addition of Copanlisib to Durvalumab can overcome resistance to Durvalumab.
Detailed Description
Treatment will be administered in outpatient settings. Durvalumab will be administered as
infusion intravenously once every two weeks on D1 and D15, every 28 days (10 mg/Kg based on
body weight). Copanlisib will be given as infusion intravenously on D1, D15 in a 28-day cycle
(flat dose). The starting dose of Copalisib will be 60 mg D1 and D15. It will be reduced to
45 mg for the first dose reduction and to 30 mg for the second dose reduction. The Durvalumab
dose will remain constant when Copanlisib is reduced.
Once the appropriate dose is determined, e.g. Copanlisib 60 mg iv d1, 15, q4w, in the
dose-finding phase, this will become the recommended dose for the dose-expansion phase.
Patients will be treated at the dose-expansion phase to increase our understanding of
pharmacokinetics and to confirm safety as well as initial efficacy in this population.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Copanlisib (30mg flat dose) | Experimental | Patients in the group will receive Durvalumab at 10mg/kg (IV infusion on days 1 and 15, q28 days). They will also receive Copanlisib at a 30mg flat dose (IV infusion on days 1 and 15, q 28 days). | |
| Copanlisib (45mg flat dose) | Experimental | Patients in the group will receive Durvalumab at 10mg/kg (IV infusion on days 1 and 15, q28 days). They will also receive Copanlisib at a 45mg flat dose (IV infusion on days 1 and 15, q 28 days). | |
| Copanlisib (60mg flat dose) | Experimental | Patients in the group will receive Durvalumab at 10mg/kg (IV infusion on days 1 and 15, q28 days). They will also receive Copanlisib at a 60mg flat dose (IV infusion on days 1 and 15, q 28 days). | |
| Copanlisib (expansion cohort) | Experimental | Patients in the group will receive Durvalumab at 10mg/kg (IV infusion on days 1 and 15, q28 days). They will also receive Copanlisib on a dose based on the results of the dose feasibility study. | |
Eligibility Criteria
Inclusion Criteria:
- Histologically confirmed NSCLC (e.g., adenocarcinoma, squamous cell) deemed
unresectable or inoperable who have received concurrent chemoradiation followed by
Durvalumab consolidation.
- Disease progression during or within 3 months of completion of Durvalumab treatment.
- Have at least one measurable lesion.
- ECOG performance status ≤2.
- Adequate organ and marrow function.
- Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
- Mixed Non-small cell and small cell histology; known EGFR and/or ALK driver mutations.
- Treated with sequential chemoradiation therapy.
- Autoimmune disease, such as rheumatoid arthritis, systemic lupus erythematosus,
requiring systemic treatment with immunosuppressant in the past two years.
- Patients who are receiving any other investigational agents orally or intravenously.
- Systemic steroid for other purpose exceeding 10 mg prednisone a day except local
injection at the discretion of the investigator.
- Solid organ or bone marrow transplant recipients.
- History or concurrent condition of interstitial lung disease of any severity and/or
severely impaired lung function.
- Patients with uncontrolled inter-current illness.
- Patients with psychiatric illness/social situations that would limit compliance with
study requirements and patients with seizure disorder not well controlled.
- Received live vaccine in the past 4 weeks.
- Pregnant or breast-feeding/lactating women.
- Receiving medications prohibited by the study.
- Left ventricular ejection fraction less than 40%.
- New York Heart Association Class 3 or above.
- Myocardial infarction within the last 6 months.
- Unstable angina.
- Venous thromboembolism within last 3 months.
- Evidence or history of bleeding diathesis. Any hemorrhage or bleeding event ≥ CTCAE
Grade 3 within 4 weeks.
- Proteinuria of ≥ CTCAE Grade 3 or estimated by urine protein: creatinine ratio > 3.5
- Major surgeries within the last 28 days.
- Any illness or medical conditions that are unstable or could jeopardize the safety of
patients and their compliance in the study.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Dose Limiting Toxicity |
| Time Frame: | 28 days |
| Safety Issue: | |
| Description: | The number of dose limiting toxicities will be counted for each cohort. |
Secondary Outcome Measures
| Measure: | Objective Response Rate |
| Time Frame: | approximately 10 years |
| Safety Issue: | |
| Description: | The objective response rate is evaluated by iRECIST 1.1, which includes all patients with partial response (iPR) or complete response (iCR). |
| Measure: | Progression-Free Survival |
| Time Frame: | approximately 10 years |
| Safety Issue: | |
| Description: | Progression-free survival (PFS) is defined as the time interval between the date patients are started on Copanlisib treatment to the date of disease progression, death or last follow-up, whichever occurs first. Patients who are intolerant to treatment and removed from study by the principal investigator or withdraw from the study will be treated as censored data for the PFS analysis. |
| Measure: | Duration of Response |
| Time Frame: | approximately 10 years |
| Safety Issue: | |
| Description: | Duration of response (DOR) is defined as the time interval between the initial response to therapy and subsequent disease progression or relapse. Non-responders will be assigned a DOR equal to zero. |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Zhonglin Hao |
Trial Keywords
- Stage 3A, 3B
- Chemoradiation therapy
- Durvalumab failure
- Copanlisib
Last Updated
May 20, 2021
