Neoplasms

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Symptoms and General Pathology

Carcinoma

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Disease Progression

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Disease Attributes

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Sirolimus

Afatinib

Erlotinib Hydrochloride

Gefitinib

Temsirolimus

MTOR Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Clotrimazole

Miconazole

Antifungal Agents

Immunosuppressive Agents

Immunologic Factors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine Kinase Inhibitors

Tyrosine

Dose escalation of the combination BIBW 2992 plus Sirolimus.

Dose escalation (19-40 patients): low or high dose oral + 12 addit. pat. at MTD, until progression or undue AEs

BIBW 2992

Dose escalation (19-40 patients): several dose levels + 12 addit. pat. at MTD until progression or undue AEs.

Sirolimus (rapamycin)

Boehringer Ingelheim

The primary objective of this trial is to identify the Maximum Tolerated Dose of BIBW 2992 therapy when given continuously in combination with Sirolimus.

The MTD will be based on the Dose Limiting Toxicity information collected during the first two cycles.

Overall safety, pharmacokinetics and anti-tumour efficacy will be evaluated as secondary objectives.

Trial of Continuous Once Daily Oral Treatment Using BIBW 2992 (Afatinib) Plus Sirolimus (Rapamune®) in Patients With Non-small Cell Lung Cancer Harbouring an EGFR Mutation and/or Disease Progression Following Prior Erlotinib or Gefitinib

A Phase Ib Open Label Clinical Trial of Continuous Once Daily Oral Treatment Using BIBW 2992 Plus Sirolimus in Patients With Non-small Cell Lung Cancer Harbouring an EGFR Mutation and/or Disease Progression Following Prior Erlotinib or Gefitinib

Number of participants with of dose limiting toxicities (DLT)

Best overall response (unconfirmed) according to RECIST v1.1

Rate of (unconfirmed) objective response, defined as complete response (CR) or partial response (PR) according to RECIST v1.1

Rate of (unconfirmed) disease control defined as CR, PR, or stable disease (SD), according to RECIST v1.1

Exploratory examination of Epidermal growth factor (receptor)(EGFR) mutations (Exons 19, 20 and 21 and others) in serum/plasma DNA and tumour DNA.

This endpoint was not analysed in the study report as the available data was too limited.

Maximum measured plasma concentration of Afatinib at steady state (Cmax,ss)

Area under the curve (AUC) of Afatinib at steady state over the dosing interval τ (AUCτ,ss) for afatinib.

Maximum measured plasma concentration of sirolimus at steady state (Cmax,ss)

Area under the curve (AUC) of sirolimus at steady state over the dosing interval τ (AUCτ,ss) for afatinib.

Percentage of participants with adverse events according to highest Common Terminology Criteria for Adverse Events (CTCAE) grade, version 3.0

Percentage of patients with drug-related adverse events (AEs).

Evaluation of laboratory parameters included assessment of the frequency of patients with ALT and AST elevations concurrent with elevated bilirubin and indicative of Hy's law cases.

Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 30mg tablet once daily plus Sir 1mg tablet once daily.

Afa30+Sir01

Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 30mg tablet once daily plus Sir 3mg tablet once daily.

Afa30+Sir03

Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 30mg tablet once daily plus Sir 5mg tablet once daily.

Afa30+Sir05

Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 30mg tablet once daily plus Sir 10mg tablet once daily.

Afa30+Sir10

Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 40mg tablet once daily plus Sir 1mg tablet once daily.

Afa40+Sir01

Patients received Sirolimus (Sir) 1mg tablet orally for 8 days, followed by oral administration of Afatinib (Afa) 40mg tablet once daily plus Sir 5mg tablet once daily.

Afa40+Sir05

Total

Age, Continuous

Sex: Female, Male

Treated set which included all patients who recieved at least one dose of the trial drug during the first and second treatment counrses.

Boehringer Ingelheim Call Center

Occurrence of Dose Limiting Toxicities (DLT)

Complete Response

Partial Response

Stable Disease

Progressive Disease

Not evaluable

Missing (baseline data only)

Best Overall Response

Objective Response

Rate of Disease Control

Treated set. This endpoint was not analysed in the study report as the available data was too limited.

Exploratory Examination of EGFR Mutations (Exons 19, 20 and 21 and Others) in Serum/Plasma DNA and Tumour DNA.

Pharmacokinetic (PK) set which included all patients in the treated set who had taken at least 1 dose of study medication and for whom at least 1 valid blood or plasma concentration was available. No patients in the Afa40+Sir05 group had analyzable data.

Maximum Measured Plasma Concentration of Afatinib at Steady State (Cmax,ss)

AUC of Afatinib at Steady State Over the Dosing Interval τ (AUCτ,ss)

Sirolimus alone (N=8, 5, 7, 1, 2, 3)

Sirolimus with Afatinib (N=6, 3, 2, 2, 1, 0)

Maximum Measured Plasma Concentration of Sirolimus at Steady State (Cmax,ss)

Sirolimus alone (N=6, 4, 7, 1, 2, 2)

Sirolimus with Afatinib (N=4, 3, 2, 2, 1, 0)

AUC of Sirolimus at Steady State Over the Dosing Interval τ (AUCτ,ss)

Grade 1

Grade 2

Grade 3

Grade 4

Grade 5

Occurrence of Adverse Events According to CTCAE, Version 3.0

Percentage of Patients With Drug-related AEs

High AST (Aspartate aminotransferase)

High ALT (Alanine aminotransferase)

High alkaline phosphatase

High total bilirubin

Frequency of Patients With Possible Clinically-significant Abnormalities in Liver Enzymes or Total Bilirubin

Run-in Period (8 Days)

Discontinued Before Starting Course 3

Discontinued After Starting Course 3

Anti-Inflammatory Agents

Docetaxel

Prednisone

Tubulin Modulators

Antimitotic Agents

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Starting doses of Docetaxel 30 mg/m\^2 IV every 3 weeks + Sirolimus 1 mg daily

Starting dose 30 mg/m\^2 by vein (IV) over about 1 hour on Day 1 of every 21 day cycle.

Docetaxel (Taxotere)

Starting dose 1 mg daily by mouth 1 time a day.

Sirolimus (Rapamycin)

5 mg by mouth twice a day with prostate cancer.

Filip Janku, MD, PHD

The goal of this clinical research study to find the highest tolerated dose of the combination of Taxotere (docetaxel) and Rapamycin (sirolimus) when given to patients with advanced cancer.

Researchers also want to find highest tolerated dose of the combination of docetaxel, sirolimus, and prednisone when given to patients with advanced prostate cancer. The safety of both drug combinations will also be studied.

The Study Drugs:

Docetaxel is designed to stop the growth of cancer cells, which may cause the cells to die. It is believed to be weakly effective at killing blood vessels in tumor tissue as well.

Sirolimus is designed to block a protein called mammalian target of rapamycin (mTOR) inside the cancer cell.

Prednisone is a corticosteroid that is similar to a natural hormone made by your body. Prednisone is often given in combination with chemotherapy to treat cancer.

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a dose level of the combination of docetaxel and sirolimus based on when you joined this study. Up to 12 dose levels of docetaxel and sirolimus will be tested. Three (3) to 6 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of docetaxel and sirolimus is found. Once the highest tolerable dose of docetaxel and sirolimus is found, up to 12 more patients may be enrolled to further study the safety of the drug at each of that dose.

If you have prostate cancer, you will also receive prednisone. All participants who receive prednisone will receive the same dose level.

Study Drug Administration:

Each study cycle is 21 days.

Everyday, you will take sirolimus by mouth 1 time a day. Sirolimus can be taken with or without food, but should be taken at the same time everyday.

On Day 1 of every cycle, you will receive docetaxel by vein over about 1 hour.

If you are taking prednisone, you will take it 2 times every day by mouth with food and water.

Study Visits:

Every week for the first 3 weeks and then about every 3 weeks, blood (about 5 teaspoons) will be drawn for routine tests. You will also have a physical exam.

Every 6 weeks, women who are able to have children will have blood drawn for a pregnancy test.

About every three weeks, blood (about 5 teaspoons) will be drawn for routine tests, to check your kidney function, and for biomarker tests.

About every 6 weeks, you will have a CT scan and x-ray to check the status of the disease.

Length of Study:

You will be on study for as long as you are benefitting. You will be taken off the study if the disease gets worse or you experience intolerable side effects.

Follow-Up:

If you experience intolerable side effects, you will be followed until the side effect has resolved or the side effect does not continue to improve or get worse. The study doctor will tell you what tests will need to be performed.

This is an investigational study. Docetaxel is FDA approved and commercially available for the treatment of advanced cancers such as breast, lung, and prostate cancer. Sirolimus is FDA approved and commercially available for the prevention of transplant rejection in kidney transplant patients. Prednisone is FDA approved and commercially available for the treatment of prostate cancer when given with docetaxel.

The combination of docetaxel and sirolimus, with or without prednisone, to treat advanced cancer is investigational. Most patients in this study will receive docetaxel and sirolimus. However, if you have prostate cancer, you will receive docetaxel, prednisone, and sirolimus.

Up to 68 patients will be enrolled in this study. All will be enrolled at MD Anderson.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Trial of Continuous Once Daily Oral Treatment Using BIBW 2992 (Afatinib) Plus Sirolimus (Rapamune®) in Patients With Non-small Cell Lung Cancer Harbouring an EGFR Mutation and/or Disease Progression Following Prior Erlotinib or Gefitinib	NCT00993499	Carcinoma, Non-...	BIBW 2992 Sirolimus (rapa...	18 Years -	Boehringer Ingelheim
Docetaxel and Sirolimus in Patients With Advanced Malignancies	NCT01054313	Advanced Cancer	Docetaxel (Taxo... Sirolimus (Rapa... Prednisone	-	M.D. Anderson Cancer Center
Docetaxel and Sirolimus in Patients With Advanced Malignancies	NCT01054313	Advanced Cancer	Docetaxel (Taxo... Sirolimus (Rapa... Prednisone	-	M.D. Anderson Cancer Center

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