MPDL3280A With Chemoradiation for Lung Cancer

NCT02525757 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: 2014-0722NCI-2015-01543
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to learn about the safety of adding MDPL3280A to standard chemotherapy (a combination of carboplatin and paclitaxel) and radiation in patients with lung cancer. You are being asked to take part in this study because you have non-small cell lung cancer (NSCLC) that is unresectable (cannot be removed by surgery) and has not spread. This is an investigational study. MPDL3280A is not FDA approved or commercially available. It is currently being used for research purposes only. Paclitaxel, carboplatin, and the radiation therapy are all FDA approved for the treatment of lung cancer. The use of these drugs in combination is considered investigational. Up to 40 participants will be enrolled in this study. All will take part at MD Anderson.

Conditions

Lung Cancer; Non-Small Cell Lung Cancer

Keywords

Lung Cancer; Non-small cell lung cancer; NSCLC; Unresectable; MPDL3280A; Carboplatin; Paraplatin; Paclitaxel; Taxol; Radiation therapy; XRT

Outcome Measures

Primary Outcomes (1)

• Time to Toxicity

  Time to toxicity defined as any grade 3, 4 regimen-related non-hematologic toxicity, during the first 15 weeks of therapy. The method of Thall et al. used for safety monitoring.

  15 weeks

Secondary Outcomes (1)

• Progression Free Survival (PFS)

  6 months and 1 year

Study Arms (2)

Group 1: Chemotherapy + Radiation

EXPERIMENTAL

Participants receive standard chemotherapy and radiation for 6-7 weeks, followed by a 3-4 week rest period when they receive no chemotherapy or radiation. Consolidation Phase: After the rest period, participants receive MPDL3280A in addition to chemotherapy for 2 cycles. Maintenance Phase: After completing the consolidation period, participants continue to receive MPDL3280A alone for up to 1 year.

Drug: MPDL3280A; Drug: Carboplatin; Drug: Paclitaxel; Radiation: Radiation Therapy

Group 2: MPDL3280A + Chemotherapy + Radiation

EXPERIMENTAL

Participants receive MPDL3280A, standard chemotherapy, and radiation therapy for 6-7 weeks. This will be followed by a rest period of 3-4 weeks, during which time participant receives 1 dose of MPDL3280A but no chemotherapy or radiation. Consolidation Phase: After the rest period, participants receive MPDL3280A in addition to chemotherapy for 2 cycles. Maintenance Phase: After completing the consolidation period, participants continue to receive MPDL3280A alone for up to 1 year.

Drug: MPDL3280A; Drug: Carboplatin; Drug: Paclitaxel; Radiation: Radiation Therapy

Interventions

MPDL3280A DRUG

1200 mg by vein every 3 weeks up to 1 year after completing consolidation chemotherapy. Group 1: MPDL3280A given after receiving standard chemotherapy and radiation for 6-7 weeks, followed by a 3-4 week rest period. Group 2: MPDL3280A given with standard chemotherapy, and radiation therapy for 6-7 weeks followed by a rest period of 3-4 weeks, during which time participants receive 1 dose of MPDL3280A but no chemotherapy or radiation.

Group 1: Chemotherapy + Radiation; Group 2: MPDL3280A + Chemotherapy + Radiation

Carboplatin DRUG

AUC 2 by vein once a week on Day 1 during radiation therapy. During consolidation chemotherapy, Carboplatin given at AUC 6 by vein on Days 1 and 22 for 2 cycles.

Also known as: Paraplatin

Group 1: Chemotherapy + Radiation; Group 2: MPDL3280A + Chemotherapy + Radiation

Paclitaxel DRUG

50 mg/m2 by vein once a week on Day 1 during radiation therapy. During consolidation chemotherapy, Paclitaxel given at 200 mg/m2 on Days 1 and 22 for 2 cycles.

Also known as: Taxol

Group 1: Chemotherapy + Radiation; Group 2: MPDL3280A + Chemotherapy + Radiation

Radiation Therapy RADIATION

60-66 Gy in 30-33 fractions administered once-daily on Day 1, 5 days a week, for 6 to 7 weeks.

Also known as: XRT

Group 1: Chemotherapy + Radiation; Group 2: MPDL3280A + Chemotherapy + Radiation

Eligibility Criteria

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

You may qualify if:

• Ability and willingness to provide informed consent
• Ability and willingness to comply with the requirements of the study protocol
• Age \>/= 18 years.
• Representative tumor specimens in paraffin blocks (preferred) or at least 10 unstained slides, with an associated pathology report, requested at any time prior to study entry. Only tissue from core needle, punch, or excisional biopsy sample collection will be accepted. Fine-needle aspiration, brushing, and lavage samples are not acceptable. For all biopsy types, submitted blocks should have sufficient tissue to generate at least 10 sections, and tissue for which the pathology report specifies that the overall tumor content is low (e.g., "sparse" or "scant") is not acceptable.
• Cont'd from #4: If archival tissue is either insufficient or unavailable, the patient will need to consent to and undergo a pre treatment core or excisional biopsy sample collection of the tumor. Fine needle aspiration, brushing, and lavage samples are not acceptable. The immediate unavailability of tissue blocks or unstained slides aside from the slides needed for diagnostic confirmation of lung cancer does not exclude patients from this trial. If the patient chooses to not undergo a repeat biopsy aside from biopsy for diagnostic purposes, the patient will still be eligible to enroll on 2014-0722. However, availability of core or excisional biopsy samples must be ascertained prior to enrollment.
• Patients must have histologically confirmed, untreated non-small cell lung cancer that are considered non-metastatic, unresectable for which chemoradiation is the definitive therapy.
• Patients will have the option to enroll on blood collection protocol, LAB09-0983, for serial collections of blood before, during intervals of treatment, and at follow up visits. Enrolling on the LAB09-0983 protocol is not required to enroll on the 2014-0722 study.
• Adequate hematologic and end organ function, defined by the following laboratory results obtained within 14 days prior to the first study treatment (Cycle 1, Day 1): Absolute neutrophil count (ANC) \>/= 1500 cells/uL \*White Blood Cells (WBC) counts \> 2500/uL \*Lymphocyte count \>/= 500/uL \*Platelet count \>/= 100,000/uL; for patients with hematologic malignancies, platelet count \>/= 75,000/uL \*Hemoglobin \>/= 9.0 g/dL \*Total bilirubin \</= 1.5 x Upper Limit of Normal (ULN) with the following exception: Patients with known Gilbert disease who have serum bilirubin level \</= 3 x ULN may be enrolled. \*Aspartate Aminotransferase (AST) and Alanine transaminase (ALT) \</= 3.0 x ULN
• Cont'd from #8: Serum creatinine \</= 1.5 x ULN or creatinine clearance \>/= 50 mL/min on the basis of the Cockcroft-Gault glomerular filtration rate estimation: (140 - age) x (weight in kg) x (0.85 if female) / 72 x (serum creatinine in mg/dL)
• Measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1
• For female patients of childbearing potential and male patients with partners of childbearing potential, agreement (by patient and/or partner) to use highly effective form(s) of contraception (i.e., one that results in a low failure rate \[\< 1% per year\] when used consistently and correctly) and to continue its use for 12 months after the last dose of MPDL3280A, and for male patients continued use of contraception must be for a minimum of 3 months post-treatment.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 as long as patients are eligible to receive chemotherapy along with concurrent radiotherapy
• International Normalized (INR) and aPTT \</= 1.5 x ULN \* This applies only to patients who do not receive therapeutic anticoagulation; patients receiving therapeutic anticoagulation (such as low-molecular weight heparin or warfarin) should be on a stable dose.

You may not qualify if:

• Patients with any distant metastasis (liver, lung, bone, brain).
• Any approved anticancer therapy, including chemotherapy, hormonal therapy, or radiotherapy, within 3 weeks prior to initiation of study treatment; however, the following are allowed: \*Hormone-replacement therapy or oral contraceptives \*Herbal therapy \> 1 week prior to Cycle 1, Day 1 (herbal therapy intended as anticancer therapy must be discontinued at least 1 week prior to Cycle 1, Day 1)
• Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis, fatty liver, and inherited liver disease
• Patients with acute leukemias, accelerated/blast phase chronic myelogenous leukemia, chronic lymphocytic leukemia, Burkitt lymphoma, plasma cell leukemia, or non-secretory myeloma
• Pregnancy, lactation, or breastfeeding
• Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
• Inability to comply with study and follow-up procedures
• History or risk of autoimmune disease, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Bell's palsy, Guillain-Barré syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis \*Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone may be eligible. \*Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen may be eligible. \*Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions: \*Patients with psoriasis must have a baseline ophthalmologic exam to rule out ocular manifestations \*Rash must cover less than 10% of body surface area (BSA)
• Cont'd from #9: \*Disease is well controlled at baseline and only requiring low potency topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, fluocinolone 0.01%, desonide 0.05%, alclometasone dipropionate 0.05%) \*No acute exacerbations of underlying condition within the last 12 months (not requiring PUVA \[psoralen plus ultraviolet A radiation\], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, high potency or oral steroids)
• History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan
• Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
• History of human immunodeficiency virus (HIV) infection or active hepatitis B (chronic or acute) or hepatitis C infection \*Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen \[HBsAg\] test and a positive anti-HBc \[antibody to hepatitis B core antigen\] antibody test) are eligible. \*Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for hepatitis C virus ribonucleic acid (HCV RNA).
• Active tuberculosis
• Severe infections within 4 weeks prior to Cycle 1, Day 1 including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
• Signs or symptoms of severe infection (sepsis) within 2 weeks prior to treatment start.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Genentech, Inc.: collaborator

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Augustyn A, Adams DL, He J, Qiao Y, Verma V, Liao Z, Tang CM, Heymach JV, Tsao AS, Lin SH. Giant Circulating Cancer-Associated Macrophage-Like Cells Are Associated With Disease Recurrence and Survival in Non-Small-Cell Lung Cancer Treated With Chemoradiation and Atezolizumab. Clin Lung Cancer. 2021 May;22(3):e451-e465. doi: 10.1016/j.cllc.2020.06.016. Epub 2020 Jun 20.

  PMID: 32798130 DERIVED

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

atezolizumab; Carboplatin; Paclitaxel; Radiotherapy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Therapeutics

Study Officials

• Steven H. Lin, MD, PHD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: August 14, 2015
• First Posted: August 17, 2015
• Study Start: January 26, 2016
• Primary Completion (Estimated): January 31, 2028
• Study Completion (Estimated): January 31, 2028
• Last Updated: February 4, 2026

Record last verified: 2026-02

Locations

US (1)