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

Vanderbilt University Medical Center

Status and phase

Terminated

Phase 2

Phase 1

Conditions

Lung Cancer

Treatments

Radiation: Radiation therapy

Drug: carboplatin

Drug: nab-paclitaxel

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00544648

VU-VICC-THO-0746

P30CA068485 (U.S. NIH Grant/Contract)

VICC THO 0746

Details and patient eligibility

About

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.

Full 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.

Enrollment

13 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria for Phase I and Phase II Patients:

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