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Carboplatin/Nab-Paclitaxel and MK-3475 in NSCLC

Information source: Hoosier Cancer Research Network
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Non-Small Cell Lung Cancer

Intervention: Carboplatin (Drug); Nab-paclitaxel (Drug); MK-3475 (Phase I) (Drug); MK-3475 (Phase II) (Drug)

Phase: Phase 1/Phase 2

Status: Recruiting

Sponsored by: Jyoti Patel

Official(s) and/or principal investigator(s):
Jyoti Patel, M.D., Study Chair, Affiliation: Hoosier Cancer Research Network

Overall contact:
Jyoti Patel, M.D., Phone: 317.921.2050, Email: ggould@hoosiercancer.org

Summary

This is a phase I/II study for previously untreated patients with advanced NSCLC. The study will take place in two phases. First, a cohort of twelve participants will be enrolled in phase I and will be treated with carboplatin, nab-paclitaxel and MK-3475 and evaluated for safety and tolerability after 2 cycles of therapy. If needed, a second cohort of twelve participants will be enrolled. Following successful completion of the dose-finding/safety run-in cohort, the study will proceed to phase II. Mandatory pre-treatment tumor biopsies will be obtained prior to initiating treatment for all participants (only if adequate archived samples are unavailable). Mandatory tumor biopsies will be obtained in the phase II part of the study after 4 cycles or at the time of progression, whichever comes first. The phase II part of the study is a single arm study. All participants will be treated with carboplatin, nab-paclitaxel, and MK-3475 at the recommended phase II dose (RP2D) in 21-day cycles for up to 4 cycles. Participants will be evaluated for response every 2 cycles (6 weeks). For participants without progression of disease after Cycle 4, MK-3475 will continue every 3 weeks for up to 2 years or until unacceptable toxicity.

Clinical Details

Official title: A Phase I/II Study of Carboplatin/Nab-Paclitaxel and MK-3475 for Advanced Non-Small Cell Lung Cancer (NSCLC)

Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

Phase I: Number of Participants with Adverse Events as a Measure of Safety and Tolerability of Recommended Phase II Dose

Phase II: Disease Assessment for Progression-Free Survival (PFS) and Objective Response Rate

Secondary outcome:

Phase I: Disease Assessment for Progression-Free Survival (PFS) and Objective Response Rate

Phase I: Disease Assessment for Anti-Tumor Activity

Phase I: Overall Survival (OS)

Phase I: Assessment of Association of PD-L1 Expression on PFS

Phase II: Overall Survival (OS)

Phase II: Disease Assessment for Anti-Tumor Activity

Phase II: Number of Participants with Adverse Events as a Measure of Safety and Tolerability

Phase II: Assessment of Association of PD-L1 Expression on PFS

Detailed description: OUTLINE: This is a multi-center study. INVESTIGATIONAL TREATMENT: Phase I, Cohort 1 Induction Therapy:

- Carboplatin AUC 6 IV, Day 1

- Nab-paclitaxel 100 mg/m2 IV, Days 1, 8, 15

- MK-3475 2 mg/kg IV, Day 1

- Cycle length: 21 days; number of cycles: 4

Phase I, Cohort 1 Maintenance Therapy: For participants who have confirmed CR, PR, or SD (non-progression) after 4 cycles of induction therapy, maintenance therapy with MK-3475 2* mg/kg will continue on Day 1 of each 21-day cycle. Treatment will continue until progression of disease, unacceptable toxicity, or for a maximum of 2 years from C1D1. If unacceptable toxicity is seen in Phase I, Cohort 1, 12 additional participants will be enrolled. Phase I, Cohort 2 Induction Therapy (if needed):

- Carboplatin AUC 6 IV, Day 1

- Nab-paclitaxel 100 mg/m2 IV, Days 1, 8, 15

- MK-3475 2 mg/kg IV, Day 1 (cycle 2-4 only)

- Cycle length: 21 days; Number of cycles: 4

Phase I, Cohort 2 Maintenance Therapy: For participants who have confirmed CR, PR, or SD (non-progression) after 4 cycles of induction therapy, maintenance therapy with MK-3475 2* mg/kg will continue on Day 1 of each 21-day cycle. Treatment will continue until progression of disease, unacceptable toxicity, or for a maximum of 2 years from C2D1. Phase II Induction Therapy:

- Carboplatin AUC 6 IV, Day 1

- Nab-paclitaxel 100 mg/m2 IV, Days 1, 8, 15

- MK-3475 RP2D IV, Day 1

- Cycle length: 21 days; number of cycles: 4

Phase II Maintenance Therapy: For participants who have confirmed CR, PR, or SD (non-progression) after 4 cycles of induction therapy, maintenance therapy with MK-3475 2* mg/kg will continue on Day 1 of each 21-day cycle. Treatment will continue until progression of disease, unacceptable toxicity, or for a maximum of 2 years from C1D1. *As additional data from ongoing trials becomes available, the dose of MK-3475 may be adjusted.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Patients must be willing and able to provide written informed consent for the trial

and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.

- Subjects must be ≥ 18 years of age.

- Individuals with stage IIIB or IV, unresectable non-small cell lung cancer (NSCLC)

who have not received prior chemotherapy for Stage IIIB or IV disease, and who are not candidates for curative surgery or radiation therapy.

- ECOG performance status (PS) 0-1

- Measurable disease by RECIST v1. 1 criteria

- Prior to registration, all participants must have adequate archival tissue available

prior to registration. If no acceptable archival tissue is available, the participant must be willing to consent to providing a mandatory pre-treatment core biopsy for research. Phase II participants must be willing to consent to providing a mandatory post-treatment core biopsy for research. Fine needle aspiration and cytology samples will not be acceptable.

- Women are eligible to participate if they are of non-childbearing potential or have

documentation of a negative pregnancy test (serum or urine β-hCG) within 3 days of registration. Sexually active pre-menopausal women of childbearing potential must agree to use adequate, highly effective contraceptive measures, starting with the first dose of study drug and for 120 days after the last dose of last study drug. Effective birth control includes (a) intrauterine device (IUD) plus one barrier method; (b) oral, implantable, or injectable contraceptives plus one barrier method; or (c) 2 barrier methods. Effective barrier methods are male or female condoms, diaphragms, and spermicides (creams or gels that contain a chemical to kill sperm). Women of childbearing potential are those who have not been surgically sterilized or have not been free from menses for ≥ 1 year.

- Male participants should agree to use an adequate method of contraception starting

with the first dose of study drug through 120 days after the last dose of last study drug. Exclusion Criteria:

- Individuals with the presence of symptomatic CNS metastases requiring radiation

treatment, surgery, or ongoing use of corticosteroids.

- Untreated or brain metastasis causing any symptoms, such as neurologic deficits or

headache. Individuals with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of study drug and any neurologic symptoms have returned to baseline and whole brain radiation or stereotactic radiosurgery completed over 4 weeks prior to registration), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to study treatment.

- History of solid organ or stem cell transplant requiring immunosuppressive

medications.

- Any prior adjuvant cytotoxic chemotherapy within 12 months of registration. Patients

who received chemotherapy for earlier stage disease more than 12 months prior to study registration are eligible for this trial.

- Has received prior therapy with an anti-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).

- Any radiotherapy within 2 weeks of registration.

- 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 of treatment.

- History of other invasive malignancy that is currently active and/or has been treated

within 12 months of registration. (Notable exceptions include: basal cell carcinoma, squamous cell carcinoma of the skin, localized prostate cancer, in situ carcinomas of the cervix and breast, and superficial bladder cancers [non-muscle-invasive]).

- Has known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

- Active autoimmune disease that has required systemic treatment in past 2 years (i. e.

with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e. g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.

- Pulmonary conditions such as sarcoidosis, silicosis, idiopathic pulmonary fibrosis,

or hypersensitivity pneumonitis.

- Has active, non-infectious pneumonitis.

- Pre-existing peripheral neuropathy that is ≥ Grade 2 by CTCAE v 4. 0 criteria.

- Known significant liver disease including viral, alcoholic, active hepatitis B or C,

and/or cirrhosis.

- Abnormal liver or renal function as defined as: bilirubin ≥ 1. 5 mg/dL; AST or ALT ≥

2. 5 x the ULN; alkaline phosphatase > 2. 5 x the ULN, there is no upper limit if bone metastasis is present in the absence of liver metastasis; creatinine > 1. 5 mg/dL

- Abnormal baseline hematologic or coagulation parameters as defined as: absolute

neutrophil count (ANC) <1. 5 x 109/L; hemoglobin < 9. 0 g/dL; platelets < 100 x 109/L; International Normalized Ratio (INR) of prothrombin time (PT) ≤ 1. 5 x ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants; Activated Partial Thromboplastin Time (aPTT) ≤ 1. 5 x ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants

- Has received a live vaccine within 30 days prior to the first dose of study drug.

- Known activating EGFR mutation or ALK translocation

- 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 pembrolizumab (MK-3475).

Locations and Contacts

Jyoti Patel, M.D., Phone: 317.921.2050, Email: ggould@hoosiercancer.org

Northwestern University, Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois 60611, United States; Recruiting
Jyoti Patel, M.D., Phone: 312-695-0184, Email: jypatel@nm.org
Rebekah Werner, Email: reworden@nm.org
Additional Information

Hoosier Cancer Research Network Website

Starting date: June 2015
Last updated: June 4, 2015

Page last updated: August 23, 2015

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