Ph I/II Nab-Paclitaxel & Carboplatin w/Concurrent Radiation Therapy for Unresectable Stg III NSCLC

NCT ID: NCT00544648

Last Updated: 2014-06-09

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-11-30
• Study Completion Date: 2014-04-30

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Nab-paclitaxel (paclitaxel albumin-stabilized nanoparticle formulation) may make tumor cells more sensitive to radiation therapy. Giving nab-paclitaxel together with radiation therapy and carboplatin may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of giving nab-paclitaxel together with carboplatin and radiation therapy and to see how well it works in treating patients with stage III non-small-cell lung cancer that cannot be removed by surgery.

Detailed Description

OBJECTIVES:

Primary

• To determine the maximum tolerated dose of nab-paclitaxel when combined concurrently with carboplatin and radiation followed by two courses of nab-paclitaxel carboplatin as consolidation. (Phase I)
• To evaluate the progression-free survival in patients with stage III unresectable non-small cell lung cancer treated with nab-paclitaxel, carboplatin, and radiotherapy followed by two courses of nab-paclitaxel with carboplatin as consolidation. (Phase II)

Secondary

• To assess safety and tolerability and identify dose-limiting toxicities in patients receiving nab-paclitaxel combined concurrently with carboplatin and radiotherapy. (Phase I)
• To assess progression-free survival, response rates, and survival. (Phase I)
• To assess overall survival and response rates in all patients treated on this study. (Phase II)
• To assess the safety and tolerability of patients receiving nab-paclitaxel combined concurrently with carboplatin and radiotherapy followed by two courses of nab-paclitaxel/carboplatin as consolidation. (Phase II) OUTLINE: This is a multicenter study.
• Phase I:

• Concurrent chemoradiotherapy: Patients receive escalating doses of nab-paclitaxel IV over 30 minutes and carboplatin IV over 30 minutes on days 1, 8, 15, 22, 29, 36, and 43. They also receive conformal radiotherapy once daily 5 days a week on days 1-5 in weeks 1-7. Patients are evaluated between weeks 8-10. Patients with disease progression are removed from study. Patients with stable disease, partial response, or complete response proceed to consolidation chemotherapy 3 weeks after completion of chemoradiotherapy.
• Consolidation chemotherapy: Patients receive nab-paclitaxel IV over 30 minutes on days 1, 8, and 15 and carboplatin IV over 30 minutes on day 1. Treatment repeats ever 21 days for up to 2 courses.
• Phase II: Patients receive concurrent chemoradiotherapy at the Maximum Tolerated Dose (MTD) of nab-paclitaxel followed by consolidation chemotherapy as in phase I.

After completion of study treatment, patients are followed at 2 months, every 3 months for 2 years, every 4 months for 2 years, and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 98 patients (15 patients for phase I and 83 patients for phase II) will be accrued for this study.

Conditions

Lung Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment

nab-paclitaxel+ carboplatin + radiation

Group Type: EXPERIMENTAL

carboplatin

Intervention Type: DRUG

(AUC 2) through a vein over 30 minutes following nab-paclitaxel, once per week x 7 weeks

nab-paclitaxel

Intervention Type: DRUG

Phase I: beginning at 40 mg/m2 through a vein over 30 minutes once per week x 7 weeks Phase II: Maximum tolerated dose through a vein over 30 minutes once per week x 7 weeks

Radiation therapy

Intervention Type: RADIATION

3D conformal radiotherapy or Intensity-Modulated Radiation Therapy (IMRT), 2.0 Gy per day x 5 days per week for 33 days during Weeks 1-7 ; Total Dose = 66 Gy

Interventions

carboplatin

(AUC 2) through a vein over 30 minutes following nab-paclitaxel, once per week x 7 weeks

Intervention Type: DRUG

nab-paclitaxel

Phase I: beginning at 40 mg/m2 through a vein over 30 minutes once per week x 7 weeks Phase II: Maximum tolerated dose through a vein over 30 minutes once per week x 7 weeks

Intervention Type: DRUG

Radiation therapy

3D conformal radiotherapy or Intensity-Modulated Radiation Therapy (IMRT), 2.0 Gy per day x 5 days per week for 33 days during Weeks 1-7 ; Total Dose = 66 Gy

Intervention Type: RADIATION

Other Intervention Names

Paraplatin; paclitaxel albumin-stabilized nanoparticle formulation; Abraxane

Eligibility Criteria

Inclusion Criteria

• Patients must voluntarily sign and date an informed consent before the initiation of any study procedures
• Patients must have non-metastatic, inoperable, Stage IIIA or IIIB histologically or cytologically documented NSCLC without evidence of malignant pleural effusion
• Patients must not have received any prior systemic chemotherapy, thoracic radiotherapy or surgical resection for treatment of NSCLC
• Patients must have at least one site of unidirectionally measurable disease as defined by Response Evaluation in Solid Tumors (RECIST) criteria
• Patients must be ≥ 3 weeks from a formal exploratory thoracotomy
• Patients must have a Radiation Oncology and Medical Oncology consult and approval prior to study entry
• Patients must be ≥ 18 years of age
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Women of childbearing potential must have a negative baseline serum pregnancy or a negative urine pregnancy test within 7 days prior to Week 1, Day 1 and must not be breast feeding.
• Women of childbearing potential and men with a sexual partner of child bearing potential must use an effective method of contraception beginning prior to study entry, for the duration of the study participation and for a minimum of 3 months after the last dose of chemotherapy.
• Patients must have adequate hepatic, renal, lung and bone marrow function as defined below:

• Absolute neutrophil count (ANC) ≥1,500/mm3
• Hemoglobin ≥ 9.0 gm/dL
• Serum Creatinine ≤1.5mg/dl
• Platelets > 100,000/mm3
• Total bilirubin ≤ upper limit of normal
• AST and ALT < 2.5 X upper limit of normal
• Alkaline phosphatase < 2.5 X upper limit of normal
• Calculated CrCl > 45 ml/min (via Cockroft-Gault formula)
• Forced expiratory volume in 1 second (FEV 1) > 800 ml

Exclusion Criteria

• Known hypersensitivity to carboplatin or nab-paclitaxel
• Peripheral neuropathy Grade ≥ 2
• Wet stage IIIB (documented malignant pleural effusion) or stage IV NSCLC
• Previous chemotherapy or radiation therapy to the chest
• Any concomitant malignancy or brain metastasis
• Any uncontrolled, clinically significant medical or psychiatric disorder
• Pregnant or nursing women
• A greater than or equal to 10% weight loss over the past 3 months

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Vanderbilt-Ingram Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Vicki Keedy, MD

Assistant Professor of Medicine; Clinical Director, Sarcoma Program; Medical Director, Clinical Trials Shared Resource; Medical Oncologist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Vicki Keedy, MD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt-Ingram Cancer Center

Locations

Purchase Cancer Group - Paducah

Paducah, Kentucky, United States

Oregon Health Sciences University

Portland, Oregon, United States

Erlanger Cancer Center at Erlanger Hospital - Baroness

Chattanooga, Tennessee, United States

Vanderbilt-Ingram Cancer Center - Cool Springs

Nashville, Tennessee, United States

Vanderbilt-Ingram Cancer Center at Franklin

Nashville, Tennessee, United States

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Countries

United States

References

Lammers PE, Lu B, Horn L, Shyr Y, Keedy V. nab-Paclitaxel in Combination With Weekly Carboplatin With Concurrent Radiotherapy in Stage III Non-Small Cell Lung Cancer. Oncologist. 2015 May;20(5):491-2. doi: 10.1634/theoncologist.2015-0030. Epub 2015 Apr 6.

Reference Type: DERIVED

PMID: 25845992 (View on PubMed)

Other Identifiers

P30CA068485

Identifier Type: NIH

Identifier Source: secondary_id

View Link

VU-VICC-THO-0746

Identifier Type: -

Identifier Source: secondary_id

VICC THO 0746

Identifier Type: -

Identifier Source: org_study_id