Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Pharmaceutical Solutions

Natriuretic Agents

Trastuzumab

Carboplatin

Docetaxel

Mannitol

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

Concentrate for solution for infusion, sterile vial 150 mg, Day 1 Cycle 1 will be a loading dose of 8 mg/kg infused over 90 minutes. Subsequent infusions will follow every 3 weeks (i.e., cycled every 21 days) with a dose of 6 mg/kg administered over 30 to 90 minutes depending on tolerability, maximum of 6 cycles.

PF-05280014

Injection concentrate single-dose vials containing 20 mg (0.5 mL) or 80 mg (2 mL), each mL contains 40 mg docetaxel (anhydrous) and 1040 mg polysorbate 80, The starting dose of Taxotere® (docetaxel) will be 75 mg/m2 administered intravenously over 60 minutes every three weeks on Day 1 of each cycle (i.e., every 21 days), maximum 6 cycles.

Taxotere®

Lyophilized powder, single-dose vials containing 50 mg, 150 mg, and 450 mg of Carboplatin for administration by intravenous infusion (each vial contains equal parts by weight of Carboplatin and mannitol), starting dose 6 AUC, over 15 minutes or longer every three weeks on Day 1 of each cycle (i.e., every 21 days), maximum 6 cycles.

Paraplatin®

Concentrate for solution for infusion, sterile vial 150 mg, Day 1 Cycle 1 will be a loading dose of 8 mg/kg infused over 90 minutes. Subsequent infusions will follow every 3 weeks (i.e., cycled every 21 days) with a dose of 6 mg/kg administered over 30 to 90 minutes depending on tolerability, maximum 6 cycles.

Trastuzumab-EU

Pfizer CT.gov Call Center

The current study will compare PK, efficacy, safety, and immunogenicity of PF-05280014 (Trastuzumab-Pfizer) in combination with Taxotere® and Carboplatin (Paraplatin) versus Herceptin® (Trastuzumab-EU) approved in the EU in combination with Taxotere® and Carboplatin (Paraplatin) in patients with operable HER2 positive, breast cancer in the neoadjuvant setting. The hypothesis to be tested in this study is the percentage of patients with steady state Cycle 5 Ctrough (Cycle 6 pre-dose) \>20 µg/mL of trastuzumab-Pfizer is similar to EU-approved trastuzumab, using a margin of -12.5%.

A Study Of PF-05280014 Or Trastuzumab Plus Taxotere® And Carboplatin In HER2 Positive Breast Cancer In The Neoadjuvant Setting (REFLECTIONS B327-04)

A RANDOMIZED, DOUBLE-BLIND PHARMACOKINETIC STUDY OF PF-05280014 PLUS TAXOTERE (REGISTERED) AND CARBOPLATIN VERSUS HERCEPTIN (REGISTERED) PLUS TAXOTERE (REGISTERED) AND CARBOPLATIN FOR THE NEOADJUVANT TREATMENT OF PATIENTS WITH OPERABLE HER2-POSITIVE BREAST CANCER

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

The percentage of participants with Cycle 5 Ctrough (Cycle 6 pre-dose) \>20 μg/mL in each treatment group, the denominator being the number of participants in the per protocol population for each treatment group.

Samples of blood were taken pre-dose on Cycles 1, 2, 4, 5, and 6, and at 1 hour post dose on Cycles 1 and 5 for pharmacokinetic evaluation.

Following surgery after treatment completion, tumors were assessed as Complete Pathological Response, Partial Pathological Response, or No Pathological Response.

ORR was defined as Complete Response (CR), Partial Response (PR), Stable (SD), Progressive Disease (PD) or Indeterminate (IND). ORR was the percentage of participants who had CR or PR at Cycle 6/End of treatment.

The number of participants with positive (titer \>=1.00) pre-dose ADA samples, participants counted towards the total if for at least one sample, the ADA was positive.

The number of participants with positive (NAb response \>=1.48) pre-dose NAb samples, participants counted towards the total if for at least one sample, the NAb was positive.

Pfizer

Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.

Participants received a loading dose of 8 mg/kg of PF-05280014 on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.

Participants received a loading dose of 8 mg/kg of trastuzumab-EU on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.

Total

Age, Continuous

Female

Sex/Gender, Customized

All participants who were randomized into the study.

It was decided that the secondary study objective to explore the relationship between drug exposure and pCR for PF-05280014 versus trastuzumab-EU would not be analyzed.

All participants who were HER2+ and randomized into the study; and who had received 6 cycles of PF-05280014 or trastuzumab-EU treatment; and had no temporary delays of PF-05280014 or trastuzumab-EU treatment lasting more than 1 week; and had no other significant protocol deviations.

Percentage of Participants With Steady State Drug Concentration Ctrough (Cycle 6 Pre-dose) >20 µg/mL at Cycle 5.

Cycle 1/Day 1 0 hours N= 101, 88

Cycle 1/Day 1 1 hour N= 97, 80

Cycle 2/Day 21 0 hours N= 99, 88

Cycle 4/Day 63 0 hours N= 98, 89

Cycle 5/Day 84 0 hours N= 101, 87

Cycle 5/Day 84 1 hour N= 90, 80

Cycle 6/Day 105 0 hours N= 101, 89

All participants who were HER2+ and randomized into the study; and who have received 6 cycles of PF-05280014 or trastuzumab-EU treatment; and had no temporary delays of PF-05280014 or trastuzumab-EU treatment lasting more than 1 week; and had no other significant protocol deviations.

Mean Predose Trastuzumab-Pfizer and Trastuzumab-EU Concentrations at Cycles 1 Through 6.

Pathologic Complete Response (pCR) Defined as the Absence of Invasive Neoplastic Cells in the Breast and Lymph Nodes.

Objective Response Rate (ORR) Defined as the Percentage of Participants Having Complete or Partial Response at End of Treatment, Based on Radiographic Assessments of the Tumor.

Cycle 1 (n=113,112)

Cycle 2 (n=111,112)

Cycle 4 (n=108,109)

Cycle 6 (n=108,108)

All participants who received at least 1 dose of study drug.

Incidence of Anti-trastuzumab Antibodies (ADAs) at Cycles 1 Through 6.

Cycle 2 (n=110,112)

Cycle 4 (n=108,110)

Incidence of Neutralizing Antibodies (NAb) at Cycles 1 Through 6.

Participants received a loading dose of 8 mg/kg of PF-05280014 on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin area under the concentration versus time curve (AUC) 6 were administered on Day 1 of each cycle.

Study

Treatment

Rare Diseases

Osteosarcoma

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Sarcoma

Soft Tissue Sarcoma

Micronutrients

Antirheumatic Agents

Dermatologic Agents

Reproductive Control Agents

Cardiotonic Agents

Anti-Infective Agents

Hematinics

Vitamins

Gemcitabine

Doxorubicin

Liposomal doxorubicin

Molgramostim

Sargramostim

Leucovorin

Methotrexate

Cisplatin

Ifosfamide

Isophosphamide mustard

Dexrazoxane

Razoxane

Mesna

Antimetabolites

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Immunosuppressive Agents

Immunologic Factors

Antidotes

Protective Agents

Trace Elements

Antineoplastic Agents, Alkylating

Alkylating Agents

Folinic Acid

Folate

Vitamin B9

Pre-Surgery, Regimen 1: Doxorubicin intravenous (IV) 90 mg daily, Cisplatin 60 mg/m\^2/day for 2 days, Methotrexate 12 gm/m\^2, Leucovorin Rescue 10 mg IV, with 10 mg orally every 6 hours; Surgery; Post-Surgery, Regimen 1: Methotrexate 12 gm/m\^2, Doxorubicin IV 90 mg, Cisplatin 60 mg/ m\^2 twice daily, Leucovorin Rescue.

Pre-Surgery, Regimen 2: Dexrazoxane 900 mg/m\^2 intravenous (IV) then Doxorubicin IV 90 mg daily, Cisplatin 120 mg/m\^2 (intra-arterial); Surgery; Post-Surgery, Regimen 2: Methotrexate 12 gm/m\^2, Leucovorin Rescue 10 mg IV, with 10 mg orally every 6 hours; Ifosfamide 2.8 grams m\^2/day and Mesna 2.8 gm/m\^2/day continuous IV over 6 days; Lung-Directed Chemotherapy, Regimen 2: Gemcitabine, Sargramostim Inhaled aerosol (5 mcg/kg, maximum dose 300 mcg).

Pre-Surgery, Regimen 1: IV Over 15 Minutes on Day 1 of Weeks 1 and 6; Post-Surgery, Regimen 1: IV on Day 1 of Weeks 16, 21, and 26; Pre-Surgery, Regimen 2: IV over 15 Minutes on Day 1 of Weeks 1, 4, and 7. Dose 90 mg/m\^2.

Pre-Surgery, Regimen 1: IV Over 48 Hours, on Days 1 and 2 of Weeks 1 and 6; Post-Surgery, Regimen 1: IV Over 48 Hours, on Days 1 and 2 of Weeks 16, 21, and 26. Pre-Surgery, Regimen 2: Infusion through an artery over 4 hours on Day 1 of Weeks 1, 4, and 7. Dose 60 mg/m\^2/day for 2 days continuous infusion.

Pre-Surgery, Regimen 1: IV Over 4 Hours on Day 1 of Weeks 4, 5, 9, and 10; Post-Surgery, Regimen 1: IV Over 4 Hours on Day 1 of Weeks 14, 15, 19, 20, 24, 25, 29, and 30; Post-Surgery, Regimen 2: IV Over 4 Hours on Day 1 of Weeks 14, 15, 20, 21, 26, 27, 32, 33, 38, and 39. Dose 12 gm/m\^2, max 20 gm over 4 hours.

Pre- and Post-Surgery, Regimen 1: IV Over 5 minutes on the day after each methotrexate dose and then by mouth every 6 hours; Post-Surgery, Regimen 2: IV Over 5 minutes on the day after each methotrexate dose and then by mouth every 6 hours. Dose 10 mg IV, with 10 mg orally every 6 hours.

Dose 900 mg/m\^2 IV Push with doxorubicin. Pre-Surgery, Regimen 2: IV Over 15 minutes on Day 1 of Weeks 1, 4, and 7.

Post-Surgery, Regimen 2: IV continuously over 5 days each time, on Weeks 16, 22, 28, and 34. Dose 2.8 gm/m\^2. Dose 2.8 grams m\^2/day.

Questionnaires to be completed on 5 different days during the study.

Questionnaire

Inhaled aerosol (5 mcg/kg, maximum dose 300 mcg) twice a day for 7 days on, 7 days off, beginning the day receive gemcitabine.

Planned limb salvage surgery after 3 courses of doxorubicin + cisplatin (IV) and High-dose methotrexate - at approximately week 12.

Surgery

IV continuously over 6 days each time, on Weeks 16, 22, 28, and 34. Dose 2.8 gm/m\^2/day.

Peter M. Anderson, MD, PhD

The goal of this clinical research study is to learn if giving certain combinations of chemotherapy drugs before and after surgery, mostly in the outpatient clinic instead of in the hospital, can result in fewer hospital stays during treatment for osteosarcoma. The drugs and schedules will vary depending on the status of the cancer and its level of risk for spreading, but they will include combinations of doxorubicin (non-liposomal), cisplatin, methotrexate, and ifosfamide, as described below.

The Study Drugs:

The standard treatment combination used to treat patients with osteosarcoma is doxorubicin, cisplatin, and methotrexate with or without ifosfamide. When this treatment combination is given in the hospital, it can require around 18-22 hospital stays. Somewhat recently, chemotherapy for osteosarcoma has become possible to give in the outpatient clinic. Researchers want to learn if giving 4 certain drugs (the combination of doxorubicin, cisplatin, and methotrexate with or without ifosfamide) in the outpatient setting to eligible patients will help to decrease the number of hospital stays.

During this study, all study participants whose tumor(s) can be taken out with surgery will be offered routine surgery to remove the tumor(s). After surgery, if the doctor believes the tumor(s) have responded well enough, the standard treatment combination is again doxorubicin, cisplatin, and methotrexate. If the tumor(s) have not responded well enough, however, the standard treatment combination is methotrexate and ifosfamide.

In this study, participants are considered at "higher risk" for the tumor(s) spreading to the lungs in the following cases: if the participant's tumor(s) are large at the time of joining this study, if the cancer has spread to other organs, and/or if standard chemotherapy in this study has not killed enough tumor cells.

The following drugs are used in this study:

* Doxorubicin is designed to stop the growth of cancer cells, which may cause the cells to die.
* Cisplatin has an atom at its center that contains a type of metal called platinum. The platinum is supposed to poison the cancer cells.
* Methotrexate is designed to disrupt cells (including cancer cells) from making and repairing DNA and "copying" themselves.
* Ifosfamide is designed to stop the growth of cancer cells, which may cause the cells to die.

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to 1 of 2 groups based on the likelihood that the surgery will be able to control the disease in the arm or leg that has the bone tumor(s).

Group 1 includes participants who are considered to have a "standard" chance that surgery will be able to control the disease in the arm or leg, participants who will have an amputation, or participants with cancer in areas other than in an arm or leg at the time of diagnosis.

Group 2 includes participants who are considered to have a "higher" chance that the tumor(s) will be left behind after having surgery that the doctor considers as "incomplete" to control the disease.

Central Venous Line:

For drugs to be given by vein, your study doctor will likely recommend that you have a central venous line (CVL) placed. A central venous line is a sterile flexible tube that will be placed into a large vein while you are under local anesthesia. Your doctor will explain this procedure to you in more detail, and you will be required to sign a separate consent form for this procedure.

Pre-Surgery Chemotherapy for Group 1:

Before surgery, Group 1 participants will receive doxorubicin, cisplatin, and methotrexate followed by leucovorin. Leucovorin is given to help prevent and/or treat the side effects that methotrexate may cause. Dexrazoxane is used to decrease the risk of side effects to the heart that doxorubicin may cause. These drugs will be given in an outpatient clinic (without requiring hospitalization), if possible.

Doxorubicin will be given by vein over 15 minutes, after dexrazoxane by vein over 15 minutes, on Day 1 of Weeks 1 and 6.

Cisplatin will be given as a continuous infusion by vein over 48 hours, on Days 1 and 2 of Weeks 1 and 6.

Methotrexate will be given by vein, over 4 hours, on Day 1 of Weeks 4, 5, 9, and 10. If you have difficulty recovering from the effects of the methotrexate therapy, you may only receive methotrexate twice before surgery, instead of 4 times.

Leucovorin will be given by vein, over 5 minutes, on the day after each methotrexate dose and then by mouth every 6 hours after that, until the study doctor believes that the methotrexate level in the blood is low. The methotrexate level in the blood will be checked using a blood test (less than 2 teaspoons each time). This test will be performed once a day after each methotrexate infusion, until the methotrexate blood level is low and it is considered safe to stop the leucovorin.

Pre-Surgery Chemotherapy for Group 2:

Before surgery, Group 2 participants will receive dexrazoxane, doxorubicin, and cisplatin.

On Day 1 of Weeks 1, 4, and 7, dexrazoxane will be given by vein over 15 minutes, followed by doxorubicin given by vein over 15 minutes and then cisplatin through an artery over 4 hours. Infusion through an artery requires a hospital stay of 2-4 days.

Surgery:

For all eligible study participants, the surgery to remove the tumor(s) will be performed on either Week 11 or 12. The surgery will be explained to you in detail, and you will be asked to sign a separate consent form for it that will describe its risks.

Before surgery, you will have routine visits with the surgeon. You will have several routine scans performed to help plan the surgery.

Chemotherapy Regimens after Surgery:

After the surgery (on or around Week 14), you will receive additional "post-surgery" chemotherapy.

After surgery, if you were originally in Group 1, and if the doctor believes the tumor(s) have responded well enough (specifically, if 90% or more of the tumor cells are dead when checked under the microscope), you will receive additional chemotherapy that is similar to what you received before surgery. This is described below as Regimen A. If the doctor does not believe the tumor(s) have responded well enough (if less than 90% of the tumor cells are dead when checked under the microscope), however, you will be assigned to Regimen B.

All participants who started in Group 2 will be assigned to Regimen B.

Radiation and Chemotherapy for Patients Ineligible for Routine Surgery:

A small number of participants on this study may need to have radiation therapy to help control the disease, as part of their routine care. This would only be done if the tumor(s) cannot be completely taken out with surgery, or if amputation is necessary but refused by the participant. If needed, and depending on where the tumor(s) are located, your doctor may decide that radiation is needed. All participants needing radiation or having surgery that the doctor considers as "incomplete" to control the disease are considered "higher risk" and will receive Regimen B therapy during and after radiation. (Radiation will usually begin during Weeks 12-14, but it could be anytime during ifosfamide therapy.) The radiation therapy will be explained to you in detail, and you will be asked to sign a separate consent form for it that will describe its risks.

Post-Surgery Chemotherapy for Regimen A:

Regimen A includes the following treatments:

* Methotrexate will be given over 4 hours on Day 1 of Weeks 14, 15, 19, 20, 24, 25, 29, and 30.
* Doxorubicin will be given on Day 1 of Weeks 16, 21, and 26.
* Cisplatin will be given as a continuous infusion by vein over 48 hours, on Days 1 and 2 of Weeks 16, 21, and 26.
* Leucovorin will be given by vein, over 5 minutes, on the day after each methotrexate dose and then by mouth every 6 hours after that, until the study doctor believes that the methotrexate level in the blood is low. The methotrexate level in the blood will be checked using a blood test (less than 2 teaspoons each time). This test will be performed once a day after each methotrexate infusion, until the methotrexate blood level is low and it is considered safe to stop the leucovorin.

Post-Surgery Chemotherapy for Regimen B:

Regimen B includes the following treatments:

* Methotrexate will be given over 4 hours on Day 1 of Weeks 14, 15, 20, 21, 26, 27, 32, 33, 38, and 39.
* Leucovorin will be given by vein, over 5 minutes, on the day after each methotrexate dose and then by mouth every 6 hours after that, until the study doctor believes that the methotrexate level in the blood is low. The methotrexate level in the blood will be checked using a blood test (less than 2 teaspoons each time). This test will be performed once a day after each methotrexate infusion, until the methotrexate blood level is low and it is considered safe to stop the leucovorin.
* Ifosfamide will be given by vein, continuously over 5 days each time, on Weeks 16, 22, 28, and 34.
* Mesna will be given by vein, continuously over 6 days each time, on Weeks 16, 22, 28, and 34. Mesna is used to decrease the risk of bleeding in the bladder and kidneys while ifosfamide is taken.

Study Tests:

After Week 5 of treatment, and then again before surgery, you will have the following tests performed:

* Your medical history will be reviewed.
* You will have a physical exam.
* Blood (about 2-3 teaspoons each time) will be collected for routine tests and tests of your kidney and liver function. The routine blood tests may be repeated more often during the weeks you are receiving any of the study drugs.

If you are receiving cisplatin, you may have a hearing test performed before each dose of this drug.

You will have an ECHO performed before your fourth dose of doxorubicin on Week 14, and possibly more often if necessary.

Questionnaires:

You will be asked to complete 5 brief questionnaires on 5 different days during this study. The questionnaires ask about the health-related quality of your life, and include questions about how you have felt, physically and emotionally, during cancer treatment. The questionnaires also ask how you and your family have adapted to your having cancer treatments, and what effects the medicines may have had on whether you have felt healthy or sick.

These questionnaires will be completed at Week 1, at about Week 7 (before surgery or radiation), sometime during Weeks 20-22, at the end-of-treatment visit (either the end-of-Regimen-A visit, the end-of-Regimen-B visit, or the end-of-treatment visit), and 1 year after your first diagnosis of cancer. It should take you about 15-20 minutes to fill out the questionnaires each time.

External Care:

If the study doctor allows and you agree, some of the blood tests in this study may be performed outside of M. D. Anderson. The study doctor will discuss this option with you, if applicable.

Length of Study Participation:

If the disease gets worse or intolerable side effects occur, you will be taken off study.

End-of-Regimen-A Visit, End-of-Regimen-B Visit, or End-of-Treatment Visit:

If you complete Regimen A or B as planned or you leave the study early for any reason, the following procedures will be performed:

* You will have a physical exam.
* Urine and blood (about 2-3 teaspoons) will be drawn for routine tests and tests of your kidney and liver function.
* You will have an ECHO, x-rays of the disease area and the chest, CT scans of the chest, and a bone scan.
* You will also have whole-body scans and a hearing test.

Follow-Up Visits:

After the end-of-Regimen-A visit, the end-of-Regimen-B visit, or the end-of-treatment visit, you will be asked to return for follow-up visits. At these visits, the following procedures will be performed:

* CT scans of the chest will be performed every 3 months for the first year after your chemotherapy ends, every 4 months for the 2nd year, every 6 months for the 3rd year, and once a year for the next 2 years.
* You will have a bone scan every year for 5 years.

This is an investigational study. All of the drugs used in this study are commercially available and commonly used in osteosarcoma. This study is designed to look at the drugs' use in the outpatient setting, which is considered research.

Up to 40 patients will take part in this study. All will be enrolled at M. D. Anderson.

Doxorubicin With Cisplatin, High-Dose Methotrexate, and Additional Risk-Adapted Outpatient Chemotherapy

Outpatient Chemotherapy in Pediatric Osteosarcoma: Doxorubicin With Cisplatin, High-Dose Methotrexate, and Additional Risk-Adapted Outpatient Chemotherapy

Treatment success defined as a patient having 6 or fewer hospitalizations during front-line chemotherapy.

M.D. Anderson Cancer Center

Expected toxicities for these varieties of osteosarcoma chemotherapy.

Pre-Surgery, Group 1: Doxorubicin intravenous (IV) 90 mg daily, Cisplatin 60 mg/m\^2/day for 2 days, Methotrexate 12 gm/m\^2, Leucovorin Rescue 10 mg IV, with 10 mg orally every 6 hours; Surgery; Post-Surgery, Regimen A: Methotrexate 12 gm/m\^2, Doxorubicin IV 90 mg, Cisplatin 60 mg/ m\^2 twice daily, Leucovorin Rescue or Regimen B: Methotrexate 12 gm/m\^2, Leucovorin Rescue 10 mg IV, with 10 mg orally every 6 hours; Ifosfamide 2.8 grams m\^2/day and Mesna 2.8 gm/m\^2/day continuous IV over 6 days; Lung-Directed Chemotherapy, Regimen B: Gemcitabine, Sargramostim Inhaled aerosol (5 mcg/kg, maximum dose 300 mcg).

Outpatient Chemotherapy

Pre-Surgery, Group 2: Dexrazoxane 900 mg/m\^2 intravenous (IV) then Doxorubicin IV 90 mg daily, Cisplatin 120 mg/m\^2 (intra-arterial); Surgery; Post-Surgery, all Group 2 assigned to Regimen B: Methotrexate 12 gm/m\^2, Leucovorin Rescue 10 mg IV, with 10 mg orally every 6 hours; Ifosfamide 2.8 grams m\^2/day and Mesna 2.8 gm/m\^2/day continuous IV over 6 days

Additional Risk-Adapted Outpatient Chemotherapy

Pre-Surgery, Group 2: Dexrazoxane 900 mg/m\^2 intravenous (IV) then Doxorubicin IV 90 mg daily, Cisplatin 120 mg/m\^2 (intra-arterial); Surgery; Post-Surgery, all Group 2 assigned to Regimen B: Methotrexate 12 gm/m\^2, Leucovorin Rescue 10 mg IV, with 10 mg orally every 6 hours; Ifosfamide 2.8 grams m\^2/day and Mesna 2.8 gm/m\^2/day continuous IV over 6 days; Lung-Directed Chemotherapy, Regimen 2: Gemcitabine, Sargramostim Inhaled aerosol (5 mcg/kg, maximum dose 300 mcg).

Male

Gender

United States

Region of Enrollment

Study could not meet accrual goal due to logistical considerations, terminated early.

Peter M. Anderson, MD, PHD / Professor

Treatment Success (6 or Fewer Hospitalizations During Front-line Chemotherapy)

Quality of Life (Ped QL) Assessment

Overall Study

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Bevacizumab

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Angiogenesis Inhibitors

Growth Inhibitors

Avastin 15 mg/kg intravenously (IV) every 3 weeks. Docetaxel 75 mg/m2 IV every 3 weeks. Carboplatin AUC 6 IV every 3 weeks.

15 mg/kg intravenously (IV) every 3 weeks

Bevacizumab (Avastin)

Vali Papadimitrakopoulou, MD

The goal of this clinical research study is to evaluate the effectiveness of Avastin® in combination with docetaxel and carboplatin in the treatment of lung cancer. The safety of this combination will also be studied.

Avastin® is a humanized monoclonal antibody that binds to vascular endothelial growth factor (VEGF). VEGF plays an important role in the growth of both normal and abnormal blood vessels. Avastin® is designed to prevent or slow down the growth of cancer cells by blocking the effects of VEGF.

Docetaxel and carboplatin are standard chemotherapy drugs that have been approved by the FDA for the treatment of NSCLC. Docetaxel and carboplatin are designed to work by stopping the division of cancer cells.

If you are found to be eligible, you will begin receiving Avastin®, docetaxel, and carboplatin. Avastin®, carboplatin, and docetaxel will be given by vein once every 3 weeks. The first dose of Avastin® will be given over 90 minutes. The second dose of Avastin® will be given over 60 minutes. All other doses of Avastin® will be given over 30 minutes. Carboplatin and docetaxel will always be given over 30 minutes. They will be given on the same day every 3 weeks (1 cycle). You may receive up to 6 cycles of treatment. You will receive standard premedication with dexamethasone to help decrease the risk of side effects. Dexamethasone will be taken before you receive your docetaxel infusion.

During the study, you will have blood tests (about 2 teaspoons) every 3 weeks to look at your blood counts. These samples will be used only for routine lab tests. You will be seen by a physician every 3 weeks and given a physical exam. Your blood pressure will be monitored, and you will be asked about any side effects you are experiencing. A performance status evaluation will also be done. In addition, you will have a urine test every 2 cycles of treatment.

After 2 cycles of treatment (6 weeks), you will have a chest x-ray and computerized tomography (CT) or magnetic resonance imaging (MRI) scan to evaluate the status of the disease. These will be repeated every 2 cycles. Your continued participation in this study depends on how your cancer responds to the study drugs. Your doctor may decide to take you off this study if you experience significant side effects or your medical condition worsens. You may continue receiving bevacizumab for as long as your cancer responds to study treatment.

You will be followed-up on by phone or at routine clinic visits for at least 12 months to monitor your condition and disease status.

This is an investigational study. Avastin® has been approved by the FDA for the treatment of colorectal cancer. Docetaxel and carboplatin are FDA approved and commercially available. The use of these drugs together in this study is experimental. A total of 50 patients will take part in this study. All participants will be enrolled at M. D. Anderson.

Avastin/Docetaxel/Carboplatin in Non-Small Cell Lung Cancer

A Phase II Evaluation of Avastin in Combination With Docetaxel and Carboplatin as Chemotherapy in Patients With Metastatic Non-Small Cell Lung Cancer

Bevacizumab has recently been demonstrated to prolong overall survival when added to carboplatin and paclitaxel for chemotherapy-naı¨ve patients with nonsquamous nonsmall-cell lung cancer (NSCLC). However, the effects of combining bevacizumab with other standards, front-line, platinum-based doublets have not been extensively explored.We designed this single treatment arm, phase 2 trial to determine whether the combination of carboplatin, docetaxel, and bevacizumab is tolerable and prolongs progression-free survival of chemotherapy-naı¨ve patients with advanced, on squamous NSCLC.

Secondary endpoints of the study included the assessment of overall survival, disease control rate (CR þPR þ SD, defined by RECIST16), and evaluation of the safety profile of this triple-agent regimen. All patients who received at least 1 dose of the study drug were analyzed for efficacy and toxicity endpoints.

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1 .0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR)= CR+ PR.

Genentech, Inc.

Up to 6 cycles of carboplatin (AUC 6), Tocetaxel (75 mg/m2), and Bevacizumab (15 mg/kg) on Day 1 every 21 days

Carboplatin,Docetaxel, and Bevacizumab

Forty patients were treated with up to 6 cycles of carboplatin (AUC 6), docetaxel (75 mg/m2), and bevacizumab (15 mg/kg) on Day 1 every 21 days. Patients with an objective response or stable disease received maintenance bevacizumab (15 mg/kg) every 21 days until disease progression. The primary endpoint was median progression-free survival. Six cycles of chemotherapy plus bevacizumab were planned. Patients who demonstrated stable disease (SD), partial response (PR), or complete response (CR) to treatment continued on single-agent bevacizumab 15 mg/kg every 21 days until disease progression or intolerable toxicity. Patients who discontinued chemotherapy before 6 cycles of treatment were also allowed to continue on single-agent bevacizumab in the absence of progressive disease (PD).

Carboplatin, Docetaxel, and Bevacizumab

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

The baseline analysis population differs from the number of participants in that the BAP does not account for the 3 patients who signed consent and screened out of the study.

Dr. John V Heymach, PHD/ Chair, Thoracic-Head & Neck Med Onc

Time to Progression-Free Survival (PFS)

Up to 6 cycles of carboplatin (AUC 6), Tocetaxel (75 mg/m2), and Bevacizumab (15 mg/kg) on Day 1 every 21 days"

Overall Survival (OS)- 5 Years

Disease Control Rate

Patients were treated with up to 6 cycles of carboplatin (AUC 6), docetaxel (75 mg/m2), and bevacizumab (15 mg/kg) on Day 1 every 21 days. Patients with an objective response or stable disease received maintenance bevacizumab (15 mg/kg) every 21 days until disease progression. The primary endpoint was median progression-free survival. Six cycles of chemotherapy plus bevacizumab were planned. Patients who demonstrated stable disease (SD), partial response (PR), or complete response (CR) to treatment continued on single-agent bevacizumab 15 mg/kg every 21 days until disease progression or intolerable toxicity. Patients who discontinued chemotherapy before 6 cycles of treatment were also allowed to continue on single-agent bevacizumab in the absence of progressive disease (PD).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study Of PF-05280014 Or Trastuzumab Plus Taxotere® And Carboplatin In HER2 Positive Breast Cancer In The Neoadjuvant Setting (REFLECTIONS B327-04)	NCT02187744	Early Breast Ca...	PF-05280014 Taxotere® Paraplatin® Trastuzumab-EU Taxotere® Paraplatin®	18 Years -	Pfizer
Doxorubicin With Cisplatin, High-Dose Methotrexate, and Additional Risk-Adapted Outpatient Chemotherapy	NCT00673179	Osteosarcoma	Doxorubicin Cisplatin Methotrexate Leucovorin Dexrazoxane Ifosfamide Questionnaire Gemcitabine Sargramostim Surgery Mesna	5 Years - 40 Years	M.D. Anderson Cancer Center
Avastin/Docetaxel/Carboplatin in Non-Small Cell Lung Cancer	NCT00271505	Non-Small Cell ...	Bevacizumab (Av... Carboplatin Docetaxel	18 Years -	M.D. Anderson Cancer Center
Avastin/Docetaxel/Carboplatin in Non-Small Cell Lung Cancer	NCT00271505	Non-Small Cell ...	Bevacizumab (Av... Carboplatin Docetaxel	18 Years -	M.D. Anderson Cancer Center
A Study Of PF-05280014 Or Trastuzumab Plus Taxotere® And Carboplatin In HER2 Positive Breast Cancer In The Neoadjuvant Setting (REFLECTIONS B327-04)	NCT02187744	Early Breast Ca...	PF-05280014 Taxotere® Paraplatin® Trastuzumab-EU Taxotere® Paraplatin®	18 Years -	Pfizer
Intraperitoneal Paclitaxel and Carboplatin With IV Avastin Therapy in Patients With Carcinomas of Mullerian Origin	NCT00652119	Ovarian Cancer Peritoneal Canc... Fallopian Tube ...	Paclitaxel Carboplatin Avastin	18 Years -	Massachusetts General Hospital

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