Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Rare Diseases

Lung Neoplasms

Small Cell Lung Carcinoma

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Small Cell Lung Cancer

Antineoplastic Agents

All Drugs and Chemicals

Etoposide

Carboplatin

Irinotecan

Bendamustine Hydrochloride

Etoposide phosphate

Topoisomerase I Inhibitors

Enzyme Inhibitors

Antineoplastic Agents, Alkylating

Alkylating Agents

This novel drug combination includes: Bendamustine, Irinotecan, and Etoposide/Carboplatin.

This study has only one arm but it incorporates two phases. Phase I utilizes a combination of bendamustine and irinotecan for Regimen A followed by etoposide and carboplatin for Regimen B.

This novel drug combination includes: Bendamustine, Irinotecan, and Etoposide/Carboplatin. Subjects will be treated with irinotecan (150 mg/m2) infusion on Day 1 followed by infusion of bendamustine on Days 1 and 2 at increasing dose levels using a 3+3 design (starting dose of 80-mg/m2/d with 20 mg/mg/d incremental increase to max 120 mg/m2/d) (Regimen A). This will be repeated every 3 weeks for a total of 3 cycles. Restaging for response will be performed prior to the next regimen.

* All subjects will then be given carboplatin (AUC 6) on day 1 and etoposide (100 mg/m2) on days 1, 2 and 3 (Regimen B). They will receive 3 cycles of this regimen every 3 weeks prior to restaging.
* At the end (3 weeks after) of the sixth total round of chemotherapy, subjects will be re-evaluated for response, and will be followed-up for recurrent disease every 8 weeks.

Novel Drug Combination

Francisco Robert, M.D.

Small cell lung cancer, or SCLC, constitutes approximately 15% of the 170,000 new cases of lung cancer diagnosed annually in the United States. Extensive-stage SCLC comprises two thirds of new cases and is generally considered sensitive to chemotherapy, despite a median time to progression of 4 months. SCLC is one of the most aggressive and lethal types of cancer, with a median survival of 9 months (range 7-11 months) in patients diagnosed with extensive disease. Overall, the majority of patients with SCLC die in less than 2 years (2-year survival rates generally less than 10%), and the 5-year survival rate is 2.3% for patients with extensive disease. The regimen of etoposide in combination with a platinum (cisplatin or carboplatin) is generally considered the "standard of care" although a recent Phase III trial suggests improved survival with the combination of cisplatin/irinotecan. Further evaluation of new agents in combination regimens attempting to overcome the intrinsic drug resistance seen in extensive-stage SCLC is warranted attempting to improve survival and achieve palliation of disease-related symptoms.

We are proposing a novel combination of bendamustine plus irinotecan followed by the standard regimen of etoposide with carboplatin. This will allow the investigation of response to the novel combination as well as any improvement in outcomes compared to historical controls.

This is a single arm, open-label, Phase I - II trial with an initial dose escalation component and an expansion cohort of patients treated at the recommended Phase II dose.

Bendamustine With Irinotecan Followed by Etoposide/Carboplatin for Patients With Extensive Stage Small Cell Lung Cancer

Phase I/IIa Study of the Novel Combination of Bendamustine With Irinotecan Followed by Etoposide/Carboplatin in Chemonaive Patients With Extensive Stage Small Cell Lung Cancer

The determination of the dose limiting toxicity as defined by The National Cancer Institute Common Toxicity Criteria version 3 as follows: grade 4 neutropenia \>5 days; grade 3/4 febrile neutropenia; grade 4 thrombocytopenia; or grade \>2 non-hematologic toxicities (except for nausea/vomiting, alopecia, or fatigue).

The degree of toxicity as defined by The National Cancer Institute Common Toxicity Criteria version 3.

Using the Response Evaluation Criteria in Solid Tumors (RECIST 2000), progression is defined as 20% or greater increase from the baseline tumor parameters or new lesions.

National Comprehensive Cancer Network

University of Alabama at Birmingham

Professor

This novel drug combination includes: Bendamustine, Irinotecan, and Etoposide/Carboplatin.This study has only one arm but it incorporates two phases. Phase I utilizes a combination of bendamustine and irinotecan for Regimen A followed by etoposide and carboplatin for Regimen B.

Novel Drug Combination: This novel drug combination includes: Bendamustine, Irinotecan, and Etoposide/Carboplatin. Subjects will be treated with irinotecan (150 mg/m2) infusion on Day 1 followed by infusion of bendamustine on Days 1 and 2 at increasing dose levels using a 3+3 design (starting dose of 80-mg/m2/d with 20 mg/mg/d incremental increase to max 120 mg/m2/d) (Regimen A). This will be repeated every 3 weeks for a total of 3 cycles. Restaging for response will be performed prior to the next regimen.

•All subjects will then be given carboplatin (AUC 6) on day 1 and etoposide (100 mg/m2) on days 1, 2 and 3 (Regimen B). They will receive 3 cycles of this regimen every 3 weeks prior to restaging.

Participants were treated with irinotecan at 150 mg/m2 on day 1 followed by bendmustine on days 1 and 2 at increasing dose levels using a 3 + 3 design. The initial dose of bendamustine was 80 mg/m2 with incremental 20 mg/m2 dose escalation to a maximum of 120 mg/m2. This was repeated every 21 days for a total of 3 cycles.

Regimen A: Cohort I Bendamustine 80 mg/m2 (Day 1,2)

Participants were treated with irinotecan at 150 mg/m2 on day 1 followed by bendmustine on days 1 and 2 at increasing dose levels using a 3 + 3 design. The initial dose of bendamustine was 100 mg/m2 with incremental 20 mg/m2 dose escalation to a maximum of 120 mg/m2. This was repeated every 21 days for a total of 3 cycles.

Regimen A: Cohort II Bendamustine 100 mg/m2 (Day 1,2)

Participants were treated with irinotecan at 150 mg/m2 on day 1 followed by bendmustine on days 1 and 2 at increasing dose levels using a 3 + 3 design. The initial dose of bendamustine was 120 mg/m2 with incremental 20 mg/m2 dose escalation to a maximum of 120 mg/m2. This was repeated every 21 days for a total of 3 cycles.

Regimen A: Cohort III Bendamustine 120 mg/m2 (Day 1,2)

Participants were treated with irinotecan at 150 mg/m2 on day 1 followed by bendmustine on days 1 and 2 at increasing dose levels using a 3 + 3 design. Bendamustine was given at 100 - 120 mg/m2. This was repeated every 21 days for a total of 3 cycles.

Regimen A: Cohort IV Bendamustine 100 -120 mg/m2 (Day 1,2)

Total

Age, Categorical

Sex: Female, Male

United States

Region of Enrollment

Francisco Robert, MD, Department of Medicine, Division of Hematology and Oncology

Phase I - Cohort I

Phase I - Cohort II

Phase I - Cohort III

There is only one arm but it incorporates two phases. Phase I utilizes a combination of bendamustine and irinotecan for Regimen A followed by etoposide and carboplatin for Regimen B.

Bendamustine, Irinotecan, Etoposide/Carboplatin (Novel drug combination): Subjects will be treated with irinotecan (150 mg/m2) infusion on Day 1 followed by infusion of bendamustine on Days 1 and 2 at increasing dose levels using a 3+3 design (starting dose of 80-mg/m2/d with 20 mg/mg/d incremental increase to max 120 mg/m2/d) (Regimen A). This will be repeated every 3 weeks for a total of 3 cycles. Restaging for response will be performed prior to the next regimen.

* All subjects will then be given carboplatin (AUC 6) on day 1 and etoposide (100 mg/m2) on days 1, 2 and 3 (Regimen B). They will receive 3 cycles of this regimen every 3 weeks prior to restaging.
* At the end (3 weeks after) of the sixth total round of chemotherapy, subjects will be re-evaluated for response, and will be followed

Number of Participants Experiencing Dose Limiting Toxicity Regimen A - Phase I

This novel drug combination includes: Bendamustine, Irinotecan, and Etoposide/Carboplatin.

This study has only one arm but it incorporates two phases. Phase I utilizes a combination of bendamustine and irinotecan for Regimen A followed by etoposide and carboplatin for Regimen B.

Novel Drug Combination: This novel drug combination includes: Bendamustine, Irinotecan, and Etoposide/Carboplatin. Subjects will be treated with irinotecan (150 mg/m2) infusion on Day 1 followed by infusion of bendamustine on Days 1 and 2 at increasing dose levels using a 3+3 design (starting dose of 80-mg/m2/d with 20 mg/mg/d incremental increase to max 120 mg/m2/d) (Regimen A). This will be repeated every 3 weeks for a total of 3 cycles. Restaging for response will be performed prior to the next regimen.

•All subjects will then be given carboplatin (AUC 6) on day 1 and etoposide (100 mg/m2) on days 1, 2 and 3 (Regimen B). They will receive 3 cycles of this regimen every 3 weeks prior to restaging.

Number of Patients With Adverse Events - Phase II

Progression Free Survival

Participants were treated with irinotecan at 150 mg/m2 on day 1 followed by bendamustine (80 mg/m2) on days 1 and 2: every 21 days for a total of 3 cycles Participants with either objective response or stable disease after 3 cycles of Regimen A, received Regimen B as a consolidation. Carboplatin AUC6 (Day 1), Etoposide 100mg/m2 (Day 1,2,3) every 21 days for 3 cycles.

Phase I - Regimen A: Cohort I (80 mg/m2) - Bendamustine (B)

Participants were treated with irinotecan at 150 mg/m2 on day 1 followed by bendamustine (100 mg/m2) on days 1 and 2: every 21 days for a total of 3 cycles.

Participants with either objective response or stable disease after 3 cycles of Regimen A, received Regimen B as a consolidation. Carboplatin AUC6 (Day 1), Etoposide 100mg/m2 (Day 1,2,3) every 21 days for 3 cycles.

Phase I - Regimen A: Cohort II 100mg/m2) - (B)

Participants were treated with irinotecan at 150 mg/m2 on day 1 followed by bendamustine (120 mg/m2) on days 1 and 2: every 21 days for a total of 3 cycles.

Participants with either objective response or stable disease after 3 cycles of Regimen A, received Regimen B as a consolidation. Carboplatin AUC6 (Day 1), Etoposide 100mg/m2 (Day 1,2,3) every 21 days for 3 cycles.

Phase I - Regimen A: Cohort III (120 mg/M2) - (B)

Participants were treated with irinotecan at 150 mg/m2 on day 1 followed by bendmustine on days 1 and 2 at bendamustine 100-120 mg/m2 (Day 1,2). This was repeated every 21 days for a total of 3 cycles.

Participants with either objective response or stable disease after 3 cycles of Regimen A, received Regimen B as a consolidation. Carboplatin AUC6 (Day 1), Etoposide 100mg/m2 (Day 1,2,3) every 21 days for 3 cycles.

Phase II - Regimen A: Cohort IV (B) 100 -120 mg/m2 (Day 1,2)

Irinotecan & Bendamustine

Regimen - B (Carboplatin & Etoposide)

Skin and Connective Tissue Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Anti-Infective Agents

Analgesics

Temozolomide

Aldesleukin

Cisplatin

Ipilimumab

Interferons

Interleukin-2

Interferon-alpha

Interferon alpha-2

Antiviral Agents

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Immunologic Factors

Analgesics, Non-Narcotic

Anti-HIV Agents

Anti-Retroviral Agents

Ipilimumab starting 1 mg/kg by vein (IV) Day 1 each cycle; Temozolomide 200 mg/m\^2 orally Days 2-5 of Induction; Cisplatin 25 mg/m\^2 IV for Days 2-4 of Induction; Interferon alfa-2b 5 million U/m2 subcutaneously on Days 1-5 of each cycle Induction + Consolidation; and Interleukin-2 9 million IU/m\^2 IV as a continuous infusion on Days 2-5 of Induction + Consolidation.

Phase I Starting dose: 1 mg/kg by vein over 90 minutes on Day 1 of each 3 week cycle for Induction 12 weeks, then Day 1 of Cycle 1 for Consolidation 12 weeks and Day 1 of each 12 week cycle in Maintenance.

Phase II dose: Maximum tolerated dose (MTD) from Phase I.

200 mg/m\^2 by mouth 1 time a day on Days 2-5 of each Induction cycle (four 3 week cycles).

25 mg/m\^2 by vein over 1 hour on Days 2-4 of each Induction cycle (four 3 week cycles).

5 million U/m2 subcutaneously on Days 2-6 of each 3 week Induction cycle (four 3 week cycles) and each 4 week Consolidation cycle (three 4 week cycles).

Interferon Alfa-2b

9 million IU/m\^2 by vein as a continuous infusion on Days 2-5 of each 3 week Induction cycle (four 3 week cycles) and each 4 week Consolidation cycle (three 4 week cycles).

Rodabe N. Amaria, MD

The goal of the Phase I part of this clinical research study is to find the highest tolerable dose of the drug Yervoy (ipilimumab) that can be given with the drugs Temodar (temozolomide), Intron-A (interferon alfa-2b), Proleukin (aldesleukin, IL-2), and Platinol (cisplatin) to patients with metastatic melanoma. The safety of this combination will also be studied in Phase I. The goal of Phase II is to learn if this combination can help to control metastatic melanoma. Note: The study was closed following Phase I enrollment.

Ipilimumab, interferon alfa-2b, and aldesleukin are designed to block the activity of cells that decrease the immune system's ability to fight cancer.

Temozolomide is designed to stop cancer cells from making new DNA (the genetic material of cells). This may stop the cancer cells from dividing into new cells.

Cisplatin is designed to poison the cancer cells, which may cause them to die.

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a study group based on when you join this study. Up to 6 groups of 3 participants will be enrolled in the Phase I portion of the study, and up to 46 participants will be enrolled in Phase II.

\*\*\*Study was halted early due to slow accrual in the Phase I portion without opening Phase II. \*\*\*

If you are enrolled in the Phase I portion, the dose of ipilimumab you receive will depend on when you joined this study. The first group of participants will receive the lowest dose level of ipilimumab. Each new group will receive a higher dose of ipilimumab than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of ipilimumab is found.

If you are enrolled in the Phase II portion, you will receive ipilimumab at the highest dose that was tolerated in the Phase I portion.

All participants will receive the same dose level of cisplatin, temozolomide, interferon alfa-2b and IL-2.

If you develop intolerable side effects while on study, your dose of IL-2 may be lowered 1-2 times until the side effects get better.

Catheter:

If you are found to be eligible to take part in this study, you will have a central venous catheter (CVC) inserted, if you do not already have one. A CVC 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.

Study Drug Administration:

The study drugs will be given in 3 stages: induction, consolidation, and maintenance.

Induction:

Induction will last 12 weeks. You will receive the study drugs in up to four 3-week cycles:

* You will receive ipilimumab by vein over 90 minutes on Day 1 of each cycle.
* You will take temozolomide by mouth 1 time a day on Days 2-5 of each cycle. You should take temozolomide on an empty stomach at least 2 hours before or after a meal. Do not open the capsule, mix it with food, or chew it.
* You will receive cisplatin by vein over 1 hour on Days 2-4 of each cycle.
* You will receive aldesleukin by vein as a continuous infusion on Days 2-5 of each cycle.
* You will receive interferon alfa-2b as an injection under your skin on Days 2-6 of each cycle.

Consolidation:

Consolidation will last 12 weeks. You will receive the study drugs in three 4-week cycles.

* You will receive ipilimumab by vein over 90 minutes on Day 1 of consolidation.
* You will receive interferon alfa-2b as an injection under your skin on Days 1-5 of each cycle.
* You will receive aldesleukin by vein as a continuous infusion on Days 2-5 of each cycle.

Maintenance:

Maintenance will last about 1½ years. You will receive ipilimumab by vein over 90 minutes on Day 1 of up to six 12-week cycles.

Other Drugs:

You will be given other drugs to help decrease the risk of side effects. The study staff will tell you about these drugs, how they will be given, and the possible risks.

Study Visits:

Before each cycle (+/- 3 days):

* You will be asked about any drugs you may be taking and any side effects you may have had.
* Your performance status will be recorded.
* Your vital signs will be measured.
* If you are able to become pregnant, you will have a blood (about 1 teaspoon) or urine pregnancy test.

Every week, blood (about 1 teaspoon) will be drawn for routine tests. Before each cycle, some of this blood will be used to check your liver and kidney function.

At the end of each cycle, you will have a physical exam, including measurement of your weight. Any tumor that can be felt with the hands will be measured during the physical exam to see if it has changed size.

Every 2 cycles (+/- 7 days), you will have a chest x-ray and CT or MRI scans to check the status of the disease.

Anytime the doctor thinks it is needed, photos of the skin lesions will be taken. Your private areas will be covered (as much as possible), and a picture of your face will not be taken unless there are lesions on your face.

Length of Study:

You may continue taking the study drugs for up to 2 years. You will no longer be able to take the study drugs if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

Your participation on the study will be over once you have completed the end-of-treatment visit and follow-up.

End-of-Treatment Visit:

Within 14 days after you stop the study therapy, the following tests and procedures will be performed:

* You will have a physical exam, including measurement of your vital signs and weight.
* Your performance status will be recorded.
* You will be asked about any drugs you may be taking and any side effects you may have had.
* Blood (about 2 tablespoons) will be drawn for routine tests.
* If the doctor thinks it is needed, you will have a CT or MRI scan.

Follow-Up:

Every 2 months for up to 3 years, you will be contacted by phone or during a clinic visit to see how you are doing.

This is an investigational study. Temozolomide, cisplatin, ipilimumab, interferon alfa-2b, and aldesleukin are FDA approved and commercially available to treat metastatic cancer. However, it is investigational to give temozolomide to patients with metastatic melanoma.

Up to 64 patients will take part in this study. All will be enrolled at MD Anderson.

IPI Biochemotherapy for Chemonaive Patients With Metastatic Melanoma

IPI-Biochemotherapy for Chemonaive Patients With Metastatic Melanoma

Tumor assessments using irRC modified World Health Organizations (WHO) criteria: Immune-Related Complete Response (irCR): Complete disappearance of all tumor lesions. Immune-Related Partial Response (irPR): decrease of 50% or greater. Immune-Related Progressive Disease (irPD): At least 25% increase in sum of products of all index lesions over baseline sum of products of diameters (SPD) calculated for index lesions. Assessment include photographic measurement of skin lesions, computed tomography scans and/or magnetic resonance imaging tumor assessments until documented tumor progression.

Bristol-Myers Squibb

M.D. Anderson Cancer Center

Carcinoma, Non-Small-Cell Lung

Amino Acids

Mitogens

Erlotinib Hydrochloride

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Tyrosine

As of 01 March 2013, OSI-906 is no longer being administered

As of 01 March 2013, the matching placebo is no longer being administered

OSI-906

Erlotinib

Placebo

Medical Director

A multicenter, randomized, double-blind, placebo-controlled, phase 2 study of Erlotinib (Tarceva®) in combination with OSI-906 in Patients with Advanced non-small cell lung cancer (NSCLC) with Activating Mutations of the Epidermal Growth Factor Receptor (EGFR) Gene who are Chemonaive.

Based on the recommendation of the Data Monitoring Committee, OSI-906 and matching placebo are no longer being administered as of 01 March 2013.

This is a multi-center, randomized (1:1), double-blind, placebo-controlled, phase 2 study. Patients will be stratified according to the following 2 parameters: (1) EGFR activating mutation type (exon 19 deletion versus exon 21 single point mutation); and (2) Eastern Cooperative Oncology Group (ECOG) performance status (0 vs. 1).

Study of Erlotinib (Tarceva®) in Combination With OSI-906 in Patients With Advanced Non-small Cell Lung Cancer (NSCLC) With Activating Mutations of the Epidermal Growth Factor Receptor (EGFR) Gene

A Randomized, Double-Blind, Phase 2 Study of Erlotinib (Tarceva®) in Combination With OSI-906 or Placebo in Chemonaive Patients With Advanced NSCLC With Activating Mutations of the Epidermal Growth Factor Receptor (EGFR) Gene

Access to anonymized individual participant level data collected during the trial, in addition to study-related supporting documentation, is planned for trials conducted with approved product indications and formulations, as well as compounds terminated during development. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.

Time from randomization to disease progression based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as assessed by investigator or death due to any cause, whichever occurs first.

Time from the date of randomization until the documented date of death.

Proportion of patients with a best overall response of complete response (CR), partial response (PR), or stable disease based on RECIST version 1.1 criteria.

Time from the date of the first documented response (CR/PR) to documented progression or death due to underlying cancer.

Defined for patients whose best overall response was CR or PR.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Bendamustine With Irinotecan Followed by Etoposide/Carboplatin for Patients With Extensive Stage Small Cell Lung Cancer	NCT00856830	Small Cell Lung... Extensive Stage... Chemonaive	Novel Drug Comb...	18 Years - 79 Years	University of Alabama at Birmingham
IPI Biochemotherapy for Chemonaive Patients With Metastatic Melanoma	NCT01409174	Melanoma	Ipilimumab Temozolomide Cisplatin Interferon Alfa... Interleukin-2	18 Years - 65 Years	M.D. Anderson Cancer Center
Study of Erlotinib (Tarceva®) in Combination With OSI-906 in Patients With Advanced Non-small Cell Lung Cancer (NSCLC) With Activating Mutations of the Epidermal Growth Factor Receptor (EGFR) Gene	NCT01221077	NSCLC Non Small Cell ...	OSI-906 Erlotinib Placebo	18 Years -	Astellas Pharma Inc

Spots Global Cancer Trial Database for chemonaive

Every month we try and update this database with for chemonaive cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for chemonaive

Every month we try and update this database with for chemonaive cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for chemonaive cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.