Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Anti-Inflammatory Agents

All Drugs and Chemicals

Anti-Infective Agents

Hydrocortisone

Hydrocortisone 17-butyrate 21-propionate

Hydrocortisone acetate

Hydrocortisone hemisuccinate

Hormones

Ketoconazole

Dutasteride

Clotrimazole

Miconazole

Antifungal Agents

Enzyme Inhibitors

Cytochrome P-450 Enzyme Inhibitors

Hormone Antagonists

Cytochrome P-450 CYP3A Inhibitors

5-alpha Reductase Inhibitors

Ketoconazole, Hydrocortisone and Dutasteride Ketoconazole: 200mg orally three times a day on an empty stomach. Hydrocortisone: 30mg in the morning and 10mg in the evening. Dutasteride: 0.5 mg once a day

Ketoconazole: 200mg orally three times a day on an empty stomach. Hydrocortisone: 30mg in the morning and 10mg in the evening. Pills should be taken with food or milk.

Dutasteride: 0.5mg orally once a day on an empty stomach or after eating a meal

Ketoconazole, Hydrocortisone and Dutasteride

Steven Balk, MD

The combination of ketaconazole and hydrocortisone is commonly used for the treatment of prostate cancer. The purpose of this study is to determine if the addition of a drug called dutasteride to this approved combination will make the combination more effective in treating prostate cancer.

* Participants will be seen by the study physician every four weeks and have a short physical examination, blood tests and be asked to provide information about their condition. Every three months they will undergo a bone scan. If the CT scan that was obtained before the participant started the study shows evidence of cancer, they will be asked to repeat this test every three months.
* Ketaconazole will be taken orally three times a day on an empty stomach. Hydrocortisone will be taken orally in the morning and at night. Dutasteride will be taken orally once a day.
* Participants may remain on study drug until there is evidence of disease progression.

Ketoconazole, Hydrocortisone and Dutasteride in Asymptomatic Hormone Refractory Prostate Cancer

A Phase II Trial of Ketoconazole, Hydrocortisone and Dutasteride in Asymptomatic Hormone Refractory Prostate Cancer

PSA decline of 50% from baseline confirmed by a PSA at least 4 weeks later.

Duration of time from treatment initiation until documented progression (PSA or Disease progression)

Massachusetts General Hospital

Dana-Farber Cancer Institute

Sunnybrook Health Sciences Centre

Oregon Health and Science University

M.D. Anderson Cancer Center

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Beth Israel Deaconess Medical Center

Principle Investigator

KHAD

Age, Categorical

Age, Continuous

Sex: Female, Male

United States

Canada

Region of Enrollment

Steven Balk

PSA Response

KHAD: ketoconazole, hydrocortisone and dutasteride for CRPC

Time to Progression

KHAD; ketoconazole, hydrocortisone and dutasteride for CRPC

Overall Study

Antineoplastic Agents

Amino Acids

Lapatinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Tyrosine

For the initial four weeks (1 cycle=28 days), participants receive KHAD treatment.

Ketoconazole: 400 mg orally 3x day Hydrocortisone: 30 mg (a.m.) and 10 mg (p.m.) orally 2x day Dutasteride: 0.5 mg orally 1x day

Participants start KHLAD on day 29 or d1 of cycle 2/ week 5. Lapatinib: 250 mg orally 1x day

Participants are treated until unacceptable toxicity, disease progression or withdrawal.

For the initial four weeks (1 cycle=28 days), participants will receive KHAD treatment.

Ketoconazole: 400 mg orally 3x day Hydrocortisone: 30 mg (a.m.) and 10 mg (p.m.) orally 2x day Dutasteride: 0.5 mg orally 1x day

Participants will start KHLAD on day 29 or d1 of cycle 2/ week 5. Lapatinib: 500 mg orally 1x day

For the initial four weeks (1 cycle=28 days), participants receive KHAD treatment.

Ketoconazole: 400 mg orally 3x day Hydrocortisone: 30 mg (a.m.) and 10 mg (p.m.) orally 2x day Dutasteride: 0.5 mg orally 1x day

Participants start KHLAD on day 29 or d1 of cycle 2/ week 5. Lapatinib: according to the established dose escalation schedule

Participants are treated until unacceptable toxicity, disease progression or withdrawal.

ketoconazole

hydrocortisone

dutasteride

lapatinib

Glenn Bubley, MD

The purpose of this research study is to determine the safety of giving ketoconazole, hydrocortisone and dutasteride (KHAD) with lapatinib. Safety is primarily based on dose limiting toxicity (DLT) evaluation at various dose levels (DL). The investigators believe that there is evidence in castrate resistant prostate cancer (CRPC) that two growth factor receptors (EGFR and Her 2/Neu) are increased in prostate cancer (PCa) cells. Both these receptors are turned off by the drug lapatinib. By adding lapatinib, the investigators hope that signaling from the receptors will be turned off and therefore make the participant's cancer more responsive to KHAD treatment.

The current study builds on investigators' KHAD experience by further targeting pathways that may still be enhancing AR activity despite reduced testosterone and DHT. Importantly, studies from several groups have shown that EGFR and Her2/Neu activation can enhance AR signaling and increase AR transcriptional activity in response to low levels of androgens. Evaluation in the clinic and lab has shown that there is increased expression of EGFR or Her2/Neu in CRPC. In addition to upregulation in EGFR and Her2/Neu protein expression, signaling through these receptors may be enhanced in some tumors by increases in growth factor levels or other mechanisms. Based on these results, the investigators suggest that EGFR and Her2/Neu contribute to enhancing AR transcriptional activity especially at low androgen levels. If this hypothesis is correct, then dual blockade of EGFR and Her2/Neu in CRPC should enhance the ability of KHAD to abrogate AR activity. Moreover, as androgens can protect PCa cells from cell death in response to EGFR/Her2/Neu/PI3 kinase pathway inhibition, we propose that KHAD plus lapatinib may be a particularly active combination therapy for CRPC.

The Phase I dose escalation schedule was to evaluate up to 4 dose levels of lapatinib as well as one step down dose for ketoconazole (-1). This is not a 'parallel assignment' since this dose escalation design proceeds in sequence not in parallel.

Ketoconazole, Hydrocortisone, Dutasteride and Lapatinib (KHAD-L) in Prostate Cancer

A Phase I/II Trial of Ketoconazole, Hydrocortisone, Dutasteride and Lapatinib (KHAD-L) in Castration Resistant Prostate Cancer With Pre- and Post-therapy Tumor Biopsies

The MTD of lapatinib in combination with KHAD is determined by the number of participants who experience a dose limiting toxicity (DLT) at the various dose levels of lapatinib under evaluation. See subsequent primary outcome measure for the DLT definition. The MTD is defined as the lapatinib dose at which fewer than one-third of patients experience a DLT. If no DLTs are observed, the MTD is not reached and the Recommended Phase II Dose (RP2D) will be based on safety and pharmacokinetic results.

A DLT is defined as an adverse event (AE) occurring during the first cycle of KHLAD treatment that are determined to related to the Lapatinib or the combination as follows:

1. Any Grade 3 or greater non-hematological treatment related (possible, probable, or definite attribution) including diarrhea
2. Grade 4 or greater for hematological toxicities, regardless of attribution.
3. Grade 3 skin reactions, pulmonary reactions, regardless of attribution.

Plasma lapatinib levels were measured after day 28 of KHLAD treatment. Participants were instructed to fast prior to samples being taken.

All grade 3-4 adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEv4 as reported on case report forms were counted to calculate the proportion of participants experiencing at least one treatment-related grade 3 or 4 AE of any type on treatment.

Brigham and Women's Hospital

Prostate Cancer Foundation Clinical Research Consortium

GlaxoSmithKline

Principal Investigator

The analysis dataset is comprised of all participants who ever started treatment. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.

Phase I Dose Level 1: KHAD+L (250 mg)

For the initial four weeks (1 cycle=28 days), participants will receive KHAD treatment.

Ketoconazole: 400 mg orally 3x day Hydrocortisone: 30 mg (a.m.) and 10 mg (p.m.) orally 2x day Dutasteride: 0.5 mg orally 1x day

Participants will start KHLAD on day 29 or d1 of cycle 2/ week 5. Lapatinib: 500 mg orally 1x day

Participants are treated until unacceptable toxicity, disease progression or withdrawal.

Phase I Dose Level 2: KHAD+L (500 mg)

Total

The analysis dataset is comprised of all enrolled participants.

This study was terminated early due to concern of exposure levels observed in PK analyses for the drug under investigation.

For the initial four weeks (1 cycle=28 days), participants receive KHAD treatment.

Ketoconazole: 400 mg orally 3x day Hydrocortisone: 30 mg (a.m.) and 10 mg (p.m.) orally 2x day Dutasteride: 0.5 mg orally 1x day

Participants start KHLAD on day 29 or d1 of cycle 2/ week 5. Lapatinib: orally 1x day according to the established dose escalation schedule

Participants are treated until unacceptable toxicity, disease progression or withdrawal.

All Phase I Participants KHAD+L

The analysis dataset is comprised of all DLT evaluable participants.

Lapatinib Maximum Tolerated Dose (MTD) [Phase I]

Lapatinib Dose Limiting Toxicity (DLT) [Phase I]

The analysis dataset is comprised of participants who received KHLAD and had an evaluable plasma sample after the first cycle (day 28).

Plasma Lapatinib Levels [Phase I]

For the initial four weeks (1 cycle=28 days), participants receive KHAD treatment.

For the initial four weeks (1 cycle=28 days), participants will receive KHAD treatment.

Ketoconazole: 400 mg orally 3x day Hydrocortisone: 30 mg (a.m.) and 10 mg (p.m.) orally 2x day Dutasteride: 0.5 mg orally 1x day Participants will start KHLAD on day 29 or d1 of cycle 2/ week 5. Lapatinib: 250 mg orally 1x day

Participants are treated until unacceptable toxicity, disease progression or withdrawal.

The analysis dataset is comprised of all participants who ever started treatment.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Ketoconazole, Hydrocortisone and Dutasteride in Asymptomatic Hormone Refractory Prostate Cancer	NCT00673127	Prostate Cancer	Ketoconazole, H...	18 Years -	Dana-Farber Cancer Institute
Ketoconazole, Hydrocortisone, Dutasteride and Lapatinib (KHAD-L) in Prostate Cancer	NCT00953576	Prostate Cancer	ketoconazole hydrocortisone dutasteride lapatinib	18 Years -	Dana-Farber Cancer Institute

Spots Global Cancer Trial Database for khad

Every month we try and update this database with for khad 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 khad

Every month we try and update this database with for khad 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 khad 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.