Rucaparib and Pembrolizumab for Maintenance Therapy in Stage IV Non-Squamous Non-Small Cell Lung Cancer

Stage IV Non-small Cell Lung Cancer Clinical Trial

Official title:

A Phase I/II Multi-site Study of Rucaparib and Pembrolizumab Maintenance Therapy in Stage IV Non-Squamous Non-Small Cell Lung Cancer After Initial Therapy With Carboplatin, Pemetrexed, and Pembrolizumab

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03559049
• Other study ID #: UMCC 2018.033
• Secondary ID: HUM00142973
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: December 24, 2018
• Est. completion date: July 2027

Study information

• Verified date: January 2024
• Source: University of Michigan Rogel Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is a multi-center, Phase I/II, single arm trial to assess the safety and efficacy of the combination of oral rucaparib plus intravenous pembrolizumab as maintenance therapy in patients with stage IV non-squamous non-small cell lung cancer (NSCLC) without progressive disease (PD), as confirmed on CT scans, after induction therapy with carboplatin/pemetrexed/pembrolizumab (CPP) triplet therapy.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 25
• Est. completion date: July 2027
• Est. primary completion date: July 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Be willing and able to provide written informed consent/assent for the trial.

• Be =18 years of age on day of signing informed consent.

• Have a life expectancy of at least 3 months.

• Have a diagnosis of stage IV non-squamous NSCLC whose tumors do not have an epidermal sensitizing growth factor (EGFR) mutation or BRAF mutation or rearrangements in ALK (anaplastic lymphoma kinase) or ROS-1 and have at least one measurable lesion based on RECIST v1.1.

• Have a performance status of 0 or 1 on the ECOG Performance Scale (Appendix 15.1).

• Demonstrate adequate organ function

• Female subject of childbearing potential should have a serum pregnancy test within -28 days of enrollment and 72 hours prior to receiving the first dose of study medications.

• Female subjects of childbearing potential must be willing to use a highly effective method of contraception as outlined in Section 6.3.3 for the course of the study through 180 days after the last dose of study medications. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

• Male subjects of childbearing potential must agree to use an adequate method of contraception as outlined in Section 6.3.3, starting with the first dose of study therapy through 180 days after the last dose of study therapy. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

• If the patient has archival tissue, this should be collected for correlative studies. If archival tissue does not exist, a new biopsy is not required

Exclusion Criteria:

• Received previous systemic therapy for stage IV NSCLC

• Received radiation to the lungs >30Gy =6 months of enrollment

• Received palliative radiation within 7 days of enrollment

• Had prior treatment with any other anti-PD-1, PD-L1, or PD-L2 agent or an antibody targeting other immune-regulatory receptors or mechanisms

• Received prior treatment with a PARP inhibitor

• Has a known history of prior malignancy except if the patient has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy

• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis

• Has active autoimmune disease that has required systemic treatment within the past 2 years

• Subjects requiring daily corticosteroids >10mg of prednisone (or its equivalent) would be excluded from the study.

• Has evidence of interstitial lung disease or a history of non-infectious pneumonitis that required oral or intravenous glucocorticoids to assist with management

• Has an active infection requiring systemic therapy

• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial

• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with informed consent through 180 days after the last dose of trial treatment

• Has a diagnosis of immunodeficiency (including Human Immunodeficiency Virus (HIV) or acquired immunodeficiency (AIDS)-related illness) or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to enrollment

• Has a known history of active TB (Bacillus Tuberculosis)

• Has known active Hepatitis B or Hepatitis C

• Has received a live vaccine within 30 days of enrollment

• A medical condition that requires daily systemic corticosteroids, greater than the equivalent of 10mg of prednisone

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Stage IV Non-small Cell Lung Cancer

Intervention

Drug:
• Pembrolizumab
200mg IV every 21 days
• Pemetrexed
500mg/m^2 IV every 21 days
• Carboplatin
AUC 5 IV every 21 days
• Rucaparib
600mg PO, BID days 1-21 of each 21 day cycle

Locations

Country	Name	City	State
United States	The University of Michigan Rogel Cancer Center	Ann Arbor	Michigan
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (3)

Lead Sponsor	Collaborator
University of Michigan Rogel Cancer Center	Clovis Oncology, Inc., Merck Sharp & Dohme LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Median duration of time from start of treatment to time of progression	The primary endpoint is median progression free survival (PFS) which is defined as the median duration of time from the start of treatment to progression. Progression is defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started, or the appearance of one or more new lesions.	Up to 5 years
Secondary	Median duration of time from the start of treatment until death	The secondary endpoint is median overall survival (OS) which is defined as the median duration of time from the start of treatment until death.	Up to 5 years
Secondary	Response rate	Percentage of patients who achieve a complete or partial response after at least one cycle of maintenance therapy with rucaparib and pembrolizumab. Response assessed by immune-related Response Evaluation Criteria in Solid Tumors (irRecist).	Up to 5 years