Phase II Trial of Sequential Consolidation With Pembrolizumab Followed by Nab-paclitaxel

NCT02684461 | Completed Phase 2 Results DMC

• 1 other identifier: LCCC 1516
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this research study is to test the effectiveness of three treatment arms that are designed to improve survival in patients with non-small cell lung cancer. Eligible subjects could be randomized to four (4) cycles of chemotherapy followed by immunotherapy, or immunotherapy followed by chemotherapy, or four cycles of chemotherapy plus immunotherapy.

Conditions

Non Small Cell Lung Cancer

Keywords

lung cancer; PD-1 antibody; immune checkpoint blockade

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  Overall survival is defined as the time from day 1 of treatment to death from any cause. Median overall survival was calculated for each arm.

  Up to 60 months

Secondary Outcomes (6)

• Progression Free Survival (PFS)

  Up to 60 months

• Overall Rates of Response (ORR)

  6 months

• Rates of Response in Arm A and Arm B

  6 months

• Toxicity Profile

  6 months

• Quality of Life (QOL) End of Treatment

  Baseline to End of Treatment (up to 210 Days)

Study Arms (3)

Arm A: Sequential Consolidation

ACTIVE COMPARATOR

Completion of four cycles of Sequential Consolidation of Pembrolizumab 200mg every 21 days and then four cycles Nab-paclitaxel 100 mg/mg2 on day 1 and day 8 every 21 days

Drug: Pembrolizumab

Arm B: Sequential Consolidation

ACTIVE COMPARATOR

Completion of 4 cycles of Sequential Consolidation of Nab-paclitexel 100 mg/m2 on day 1 and day 8 every 21 days and then Pembrolizumab 200 mg every 21

Drug: Pembrolizumab

Arm C: Concurrent Consolidation

ACTIVE COMPARATOR

Concurrent Consolidation of Nab paclitaxel 100 mg/m2 on day 1 and day 8 plus Pembrolizumab 200 m5 on day 1 every 21 days for four cycles

Drug: Pembrolizumab

Interventions

Pembrolizumab DRUG

Receive Pembrolizumab 200 mg on day 1 every 21 days for four cycles. Receive nab-paclitaxel 100 mg/m2 on day 1 and day 8 every 21 days for four cycles.

Also known as: Keytruda, nab-paclitaxel

Arm A: Sequential Consolidation; Arm B: Sequential Consolidation; Arm C: Concurrent Consolidation

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be willing and able to provide written informed consent for this trial
• Be greater than or equal to 18 years of age on day of signing consent
• Eastern Cooperative Oncology Group Performance Status less than or equal to 1
• Histologically or cytologically confirmed confirmed stage IV (metastatic) non small cell lung cancer as defined by American Joint Committee on Cancer (AJCC). Recurrent but not metastatic disease is allowed if deemed incurable.
• Has completed or scheduled to begin 4-6 cycles of platinum based induction chemotherapy that does not include a taxane
• Induction may contain, but is not require to contain bevacizumab or cetuximab.
• Induction with a platinum doublet plus another biologic agent will be allowed following review by the University of North Carolina principal investigator that thee is no additional risk to the subject
• NOTE: Evaluable disease is not required for study entry (patients with complete response or response sufficient to preclude measurable lesions are not excluded; such patients will be evaluated for progression free survival and overall survival, but not response)
• Demonstrate adequate organ function (defined in protocol). All screening labs should be performed within 14 days of treatment initiation.
• Recovered from all reversible toxicities related to their previous treatment (other than alopecia) less than or equal to grade 1 or baseline; exceptions to this criteria may be allowed at the discretion of the overall principal investigator for toxicities that are not expected to be exacerbated by pembrolizumab or nab paclitaxel
• Patients with brain metastases may participate if they have undergone appropriate treatment for the lesion)s), are at least two weeks post treatment without evidence for post-treatment progression, have no significant neurologic symptoms, and no longer require steroids for the reason of brain metastases
• Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for greater than 1 year. The two birth control methods can be two barrier methods or a barrier method plus a hormonal method to prevent pregnancy. Subjects should start using birth control from study Visit 1 throughout the study period up to 120 days after the last dose of study therapy.
• Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.

You may not qualify if:

• Patients with epidermal growth factor receptor (EGFR) mutations expected to be sensitive to epidermal growth factor receptor (EGFR) inhibitors and patients with Echinoderm Microtubule-Associated Protein like 4 anaplastic lymphoma kinase (EML4/ALK) translocations are excluded, unless all available FDA approved targeted therapy options have been utilized. NOTE: In contrast to the above a patient with an EGFR mutation who has been treated with a first-generation and third generation TKIs and then with four cycles of carboplatin plus pemetrexed would be eligible
• Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose treatment
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1. Note: if subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
• Has had a prior monoclonal antibody within 4 weeks prior to study day 1 or who has not recovered from adverse events due to agents administered more than 4 weeks earlier. Exceptions to these criteria may be allowed at the discretion overall principal for toxicities that are not expected to be exacerbated by pembrolizumab or nab-paclitaxel
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy
• Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents; subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study
• Has evidence of interstitial lung disease or active, non-infectious pneumonitis
• Has an active infection requiring systemic therapy
• Has a history or current evidence of any condition, therapy or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
• Has inadequate home environment or social support to safely complete the trial procedures
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
• Has received prior therapy with an anti-programmed cell death-1 (PD-1) , anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
• Known hypersensitivity to protein bound paclitaxel

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (5)

UNC Lineberger Comprehsive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

Rex Cancer Center

Raleigh, North Carolina, 27607, United States

Location

Rex Cancer Center of Wakefield

Raleigh, North Carolina, 27614, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Inova Schar Cancer Institute

Fairfax, Virginia, 22031, United States

Location

Related Links

• UNC Lineberger Comprehensive Cancer Center

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

pembrolizumab; 130-nm albumin-bound paclitaxel

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Melahat Canter
• Organization: University of North Carolina Lineberger Comprehensive Cancer Center

gmelahat@med.unc.edu

(919) 962-0000

Study Officials

• Jared Weiss, MD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2016
• First Posted: February 18, 2016
• Study Start: September 13, 2016
• Primary Completion: November 19, 2021
• Study Completion: November 19, 2021
• Last Updated: June 3, 2022
• Results First Posted: June 3, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)