Abraxane and Alimta in Advanced Solid Tumors

NCT00470548 | Terminated Phase 1 Results DMC FDA Drug

• 4 other identifiers: UCDCC#185224355ABX027H3E-US-I017
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as paclitaxel albumin-stabilized nanoparticle formulation, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Pemetrexed may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving paclitaxel albumin-stabilized nanoparticle formulation together with pemetrexed may kill more tumor cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of paclitaxel albumin-stabilized nanoparticle formulation when given together with pemetrexed and to see how well they work in treating patients with advanced non-small cell lung cancer, breast cancer, or other solid tumors.

Conditions

Breast Cancer; Lung Cancer; Unspecified Adult Solid Tumor, Protocol Specific

Keywords

male breast cancer; recurrent breast cancer; stage IIIA breast cancer; stage IIIB breast cancer; stage IIIC breast cancer; stage IV breast cancer; stage IIIA non-small cell lung cancer; stage IIIB non-small cell lung cancer; stage IV non-small cell lung cancer; recurrent non-small cell lung cancer; unspecified adult solid tumor, protocol specific

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Dose Limiting Toxicities

  Dose limiting toxicity (DLT) was defined as any of the following occurring during the first cycle: Grade 4 thrombocytopenia, or grade 3 thrombocytopenia associated with bleeding, requirement for transfusion, febrile neutropenia, neutropenia with documented infection. Non-hematologic DLT included any other ≥ grade 3 non-hematologic toxicity that was clinically significant and considered by the investigator to be related to study drug. Alopecia and grade 3 allergic reaction/hypersensitivity with infusion were not considered DLTs.

  Up to21 days

• Number of Patients With Toxicities

  Toxicities was evaluated based on the standard NCI CTCAE Version 3.0 grading criteria. Attributable grade ≥ 3 hematologic and non-hematologic toxicities are presented here.

  Up to 1 year

Secondary Outcomes (5)

• Duration of Overall Survival

  Up to 2 years

• Number of Participants With Complete Response

  Up to 2 years

• Number of Participants With Stable Disease

  Up to 2 years

• Number of Participants With Partial Response

  Up to 2 years

• Number of Participants With Disease Control

  Up to 2 years

Study Arms (2)

Phase I: Abraxane and Alimta

EXPERIMENTAL

Three dose levels were tested. Pemetrexed 500mg/m2 day 1 and nab-paclitaxel day 1 at 180, 220, and 260 mg/m2 every 21 days.

Drug: Abraxane; Drug: Alimta

Phase II: Abraxane and Alimta

EXPERIMENTAL

Pemetrexed 500mg/m2 day 1 and nab-paclitaxel day 1 at 260 mg/m2 every 21 days.

Drug: Abraxane; Drug: Alimta

Interventions

Abraxane DRUG

ABI-007 IV administration following pemetrexed on Day 1 of each cycle (infused over 30 minutes)

Also known as: paclitaxel albumin-stabilized nanoparticle formulation, ABI-007

Phase I: Abraxane and Alimta; Phase II: Abraxane and Alimta

Alimta DRUG

Pemetrexed IV administration on Day 1 of each cycle (infused over 10 minutes)

Also known as: pemetrexed disodium

Phase I: Abraxane and Alimta; Phase II: Abraxane and Alimta

Eligibility Criteria

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

You may qualify if:

• For the phase II portion patients must have cytologically or histologically proven selected stage IIIB (pleural effusion) or IV NSCLC.
• For the phase II portion patients must have NSCLC that has progressed or recurred after treatment with platinum-based therapy.
• No prior pemetrexed. Prior Taxol is allowed. Prior ABI 007 is not allowed.
• Patients must have measurable disease by RECIST criteria for the phase II portion.
• Patients must be 18 years of age or older.
• Patients must have a performance status of 0 -2
• Patients must have an estimated survival of at least 3 months.
• Any prior chemotherapy must have been completed at least 4 weeks prior to start of treatment.
• Patients must have adequate renal function as documented by a calculated creatinine clearance of \> 45 ml/min
• Patients must have adequate liver functions: AST and ALT \< 2.5 X upper limit of normal, and bilirubin \< upper limit of normal.
• Patients must have adequate bone marrow function: Platelets \>100,000 cells/mm3 and ANC \> 1,500 cells/mm3.
• For patients who have baseline clinically significant pleural or peritoneal effusions (on the basis of symptoms or clinical examination) before initiation of pemetrexed therapy, consideration should be given to draining the effusion prior to dosing.
• Patients with asymptomatic treated brain metastasis (surgical resection or radiotherapy) may be included if they are neurologically stable and have been off steroids and anticonvulsants for at least 4 weeks.
• Patients must be able to take and retain oral medication.
• Ability to take folic acid, vitamin B12 and dexamethasone according to protocol.

You may not qualify if:

• Pregnant or breastfeeding women.
• Patient with pre-existing peripheral neuropathy of NCI CTCAE Version 3.0 of grade 2.
• Patient has a clinically significant concurrent illness.
• Patient is currently enrolled in a different clinical study in which investigational procedures are performed or investigational therapies are administered.
• Patient has a history of allergy or hypersensitivity to the study drugs or a taxane.
• Patient has serious medical risk factors involving any of the major organ systems such that the investigator considers it unsafe for the patient to receive an experimental research drug.
• Prior therapy with pemetrexed, or ABI-007.
• Patient is receiving treatment with any excluded concomitant medication.
• Presence of third space fluid which cannot be controlled by drainage.

Sponsors & Collaborators

• University of California, Davis: lead
• Celgene: collaborator
• Eli Lilly and Company: collaborator

Study Sites (1)

University of California Davis Cancer Center

Sacramento, California, 95817, United States

Location

Related Publications (1)

• Ho C, Davies AM, Sangha RS, Lau D, Lara P Jr, Chew HK, Beckett L, Mack PC, Riess JW, Gandara DR. Phase I/II trial of pemetrexed plus nab-paclitaxel in advanced solid tumor patients with emphasis on non-small cell lung cancer. Invest New Drugs. 2013 Dec;31(6):1587-91. doi: 10.1007/s10637-013-0024-y. Epub 2013 Sep 8.

  PMID: 24013936 RESULT

MeSH Terms

Conditions

Breast Neoplasms; Lung Neoplasms; Breast Neoplasms, Male; Carcinoma, Non-Small-Cell Lung

Interventions

Albumin-Bound Paclitaxel; Taxes; Pemetrexed

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Intervention Hierarchy (Ancestors)

Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Economics; Health Care Economics and Organizations; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic

Limitations and Caveats

The phase II portion accrued 37 patients before early closure due to increasing the first-line pemetrexed/platinum doublet use in non-squamous NSCLC.

Results Point of Contact

• Title: Analyst
• Organization: University of California Davis

pkaujla@ucdavis.edu

916 734 0294

Study Officials

• David R. Gandara, MD

  University of California, Davis

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 3, 2007
• First Posted: May 7, 2007
• Study Start: April 1, 2007
• Primary Completion: October 1, 2014
• Study Completion: October 1, 2014
• Last Updated: January 10, 2018
• Results First Posted: March 8, 2017

Record last verified: 2018-01

Locations

US (1)