A Study of Nivolumab +/- Nab-paclitaxel in Non-small Cell Lung Cancer

NCT02967133 | Terminated Phase 2 Results DMC

• 1 other identifier: AFT-31
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 4

Brief Summary

The optimal prioritization of second-line chemotherapy and immune therapy based on demographic or biomarker data is an area of ongoing investigation. The hypothesis of this study is that there may be an additive or synergistic antitumor effect of combined chemotherapy and nivolumab in the second-line treatment of NSCLC as an important concept to test in a clinical trial. Previously treated NSCLC remains a setting of unmet clinical need despite recent clinical research progress. Early progression for a subset of NSCLC patients receiving nivolumab is a specific area of clinical need.

Conditions

Non-Small-Cell Lung Cancer Metastatic; Non-Small Cell Carcinoma of Lung, TNM Stage 4; Nonsmall Cell Lung Cancer; Non Small Cell Lung Cancer Recurrent

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival

  This study will compare the progression-free survival of patients with advanced stage non-small cell lung cancer whose cancer has progressed after standard first-line platinum based doublet chemotherapy is improved with nivolumab plus nab-paclitaxel compared to nivolumab alone. A progression is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions). Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.

  13 months

Study Arms (2)

Arm A

ACTIVE COMPARATOR

Nivolumab q 14 days until disease progression/toxicity

Drug: Nivolumab

Arm B

ACTIVE COMPARATOR

Nivolumab every 21 days until disease progression Nab-paclitaxel every 21 days

Drug: Nivolumab; Drug: nab-paclitaxel

Interventions

Nivolumab DRUG

Arm A: Nivolumab 240 mg via intravenous infusion (IV) over 30 minutes day 1 of each 14 day cycle until disease progression or not tolerated. Arm B: Nivolumab 360 mg via intravenous infusion (IV) over 30 minutes day 1 of every 21 day treatment cycle until progression or not tolerated.

Also known as: Opdivo

Arm A; Arm B

nab-paclitaxel DRUG

Patients in arm B receive nab-paclitaxel at a dose of 100 mg/m2 over intravenous infusion on Days 1 and 8 of each 21 day cycle.

Also known as: abraxane

Arm B

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed, Stage IV non-small cell lung cancer (per the Union Internationale contre le Cancer/American Join Committee on Cancer staging system, 7th edition) or recurrent incurable non-small cell lung cancer that has progressed after first-line chemotherapy.
• Prior Therapy: Platinum doublet chemotherapy for current diagnosis of advanced lung cancer. Only one prior line of chemotherapy for advanced lung cancer allowed. Adjuvant chemotherapy, neoadjuvant chemotherapy, or chemoradiotherapy given for early stage lung cancer at least 6 months prior to diagnosis of recurrent/metastatic disease is not counted as a line of therapy for advanced lung cancer. Patients who received platinum doublet therapy with or without radiotherapy as part of treatment for early stage non-small cell lung cancer less than 6 months after developing stage 4 or recurrent incurable disease will be considered study eligible by the criterion of having received one line of chemotherapy for non-small cell lung cancer.
• EGFR, ALK and ROS biomarker positive tumors are eligible as long as the patient has received at least one standard oral, molecular inhibitor therapy in addition to standard platinum doublet chemotherapy. More than one molecular inhibitor is allowed such as a first generation EGFR inhibitor followed by a next generation EGFR inhibitor when T790 mutation develops. Prior molecular therapy for biomarker positive tumors such as (but not limited to) MET, RET and BRAF allowed but not required.
• Prior chemotherapy must have been completed 21 days prior to initiation of protocol therapy and all toxicities must \< grade 2.
• Patients must have \< Grade 2 or pre-existing neuropathy (per CTCAE).
• Palliative radiation must have been completed 2 weeks prior to the initiation of study therapy.
• All patients must have measurable disease. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 20mm with conventional techniques or as ≥10mm with spiral CT scan.
• ECOG Performance Status: 0-1
• Second malignancy: No "currently active" second malignancy other than non-melanoma skin cancers.
• Brain metastases: brain metastases must have been treated at least 2 weeks prior to enrollment, be asymptomatic from brain metastases, stable on brain imaging, and not be receiving a supra-physiologic dose of steroids (\> 10 mg prednisone daily or equivalent).
• Non-pregnant and non-nursing. The effect of nab-paclitaxel and nivolumab on the fetus is unknown.
• Women of childbearing potential (WOCBP) must 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 6 months after the last dose of study medication. Patients of childbearing potential are those who have not been surgically sterilized or have not been free of menses \> 1 year.
• Male patients must agree to use an adequate method of contraception starting with the first dose of study therapy through 7 months after the last dose of study therapy.
• Age ≥18 years.
• Required Initial Laboratory Values:

You may not qualify if:

• Prior nab-paclitaxel chemotherapy excluded.
• Prior immune therapy for NSCLC excluded. Patients should be excluded if they have had prior treatment with an anti-PD-1, anti-PD-L1, anti PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways.
• Patients will be excluded if they have an active, known or suspected autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.
• Patients will be excluded if they have a condition requiring systemic treatment with either corticosteroids (\>10mg/day prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses \>10 mg daily prednisone equivalents are permitted in the absence or active autoimmune disease.
• Patients should be excluded if they test positive for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection.
• Patients should be excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
• Allergies and Adverse Drug Reaction: History of allergy to study drug components

Sponsors & Collaborators

• Alliance Foundation Trials, LLC.: lead
• Celgene Corporation: collaborator
• Bristol-Myers Squibb: collaborator

Study Sites (4)

St. Elizabeth's Healthcare

Edgewood, Kentucky, 41017, United States

Location

Metro Minnesota community oncology research consortium

Saint Louis Park, Minnesota, 55416, United States

Location

Missouri Baptist Medical Center

St Louis, Missouri, 63131, United States

Location

Nebraska Methodist Hospital

Omaha, Nebraska, 68114, United States

Location

Related Publications (13)

• Brahmer J, Reckamp KL, Baas P, Crino L, Eberhardt WE, Poddubskaya E, Antonia S, Pluzanski A, Vokes EE, Holgado E, Waterhouse D, Ready N, Gainor J, Aren Frontera O, Havel L, Steins M, Garassino MC, Aerts JG, Domine M, Paz-Ares L, Reck M, Baudelet C, Harbison CT, Lestini B, Spigel DR. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. N Engl J Med. 2015 Jul 9;373(2):123-35. doi: 10.1056/NEJMoa1504627. Epub 2015 May 31.

  PMID: 26028407 BACKGROUND

• Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, Chow LQ, Vokes EE, Felip E, Holgado E, Barlesi F, Kohlhaufl M, Arrieta O, Burgio MA, Fayette J, Lena H, Poddubskaya E, Gerber DE, Gettinger SN, Rudin CM, Rizvi N, Crino L, Blumenschein GR Jr, Antonia SJ, Dorange C, Harbison CT, Graf Finckenstein F, Brahmer JR. Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. N Engl J Med. 2015 Oct 22;373(17):1627-39. doi: 10.1056/NEJMoa1507643. Epub 2015 Sep 27.

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• Socinski MA, Bondarenko I, Karaseva NA, Makhson AM, Vynnychenko I, Okamoto I, Hon JK, Hirsh V, Bhar P, Zhang H, Iglesias JL, Renschler MF. Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: final results of a phase III trial. J Clin Oncol. 2012 Jun 10;30(17):2055-62. doi: 10.1200/JCO.2011.39.5848. Epub 2012 Apr 30.

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• Liu Z, Wei Z, Hu Y, Gao F, Hao L, Fang P, Sun S, Li J, Jiao S. A phase II open-label clinical study of comparing nab-paclitaxel with pemetrexed as second-line chemotherapy for patients with stage IIIB/IV non-small-cell lung cancer. Med Oncol. 2015 Aug;32(8):216. doi: 10.1007/s12032-015-0660-5. Epub 2015 Jul 14.

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• Camidge R. et al. ORAL02.05 Safety and Efficacy of First-Line Nivolumab (NIVO; Anti-Programmed Death-1 [PD-1]) and Ipilimumab in Non-Small Cell Lung Cancer (NSCLC) World Lung Cancer Meeting, Denver, CO September 2015.

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  BACKGROUND

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Nivolumab; 130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins

Results Point of Contact

• Title: Neal Ready MD PhD
• Organization: Duke University Medical Center

neal.ready@duke.edu

(919) 681-6932

Study Officials

• Monica Bertagnolli, MD

  Alliance Foundation Trials, LLC.

  PRINCIPAL INVESTIGATOR

• Neal Ready, MD, PhD

  Alliance Foundation Trials, LLC.

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: November 8, 2016
• First Posted: November 18, 2016
• Study Start: December 1, 2016
• Primary Completion: January 1, 2018
• Study Completion: January 1, 2018
• Last Updated: September 8, 2022
• Results First Posted: September 8, 2022

Record last verified: 2022-08

Locations

US (4)