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NCT00953576: KHLAD

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

Terminated Phase 1, PHASE2 Results posted Last updated 4 September 2018
What this trial tests

Phase 1, PHASE2 trial testing ketoconazole in Prostate Cancer in 11 participants. Terminated before completion.

Timeline
29 September 2009
Primary endpoint
11 April 2013
11 April 2013

Quick facts

Lead sponsorDana-Farber Cancer Institute
PhasePhase 1, PHASE2
StatusTerminated
Study typeINTERVENTIONAL
Allocationnon randomized
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment11
Start date29 September 2009
Primary completion11 April 2013
Estimated completion11 April 2013
Sites2 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Dana-Farber Cancer Institute

Who can join

18 and older, male only, with Prostate Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Lapatinib Maximum Tolerated Dose (MTD) [Phase I] Primary · The evaluation for MTD occurred continuously through one cycle of KHLAD treatment (28 days).

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.

GroupValue95% CI
All Phase I Participants KHAD+LNA
Lapatinib Dose Limiting Toxicity (DLT) [Phase I] Primary · The evaluation for DLT occurred continuously through one cycle of treatment (28 days).

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.

GroupValue95% CI
Phase I Dose Level 1: KHAD+L (250 mg)0
Phase I Dose Level 2: KHAD+L (500 mg)2
Plasma Lapatinib Levels [Phase I] Primary · After first 28 days of KHLAD treatment

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

GroupValue95% CI
Phase I Dose Level 1: KHAD+L (250 mg)731416 – 1424
Phase I Dose Level 2: KHAD+L (500 mg)1506680 – 2186
Grade 3-4 Treatment-Related Adverse Events Rate Secondary · Assessed each cycle throughout treatment. Treatment duration in months was a median (range) of 5.4 months (range 1 day-8.3 months). Thus, AEs were evaluated up to 8.3 months.

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.

GroupValue95% CI
Phase I Dose Level 1: KHAD+L (250 mg)00.0 – 0.451
Phase I Dose Level 2: KHAD+L (500 mg)0.400.076 – 0.811

Adverse events — posted to ClinicalTrials.gov

Time frame: Assessed each cycle throughout treatment. Median (range) treatment duration (months) for dose level 1: 5.5 (1.8-8.3) and dose level 2: 5.4 (0.2-17.9). Thus, AEs were followed up to 17.9 months.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Phase I Dose Level 1: KHAD+L (250 mg)
Serious: 0/4 (0%)
Deaths: 0/4
Phase I Dose Level 2: KHAD+L (500 mg)
Serious: 2/5 (40%)
Deaths: 0/5

Serious adverse events (2 terms)

ReactionSystemPhase I Dose Level 1: KHAD…Phase I Dose Level 2: KHAD…
Cardiac-otherCardiac disorders
HypophosphatemiaMetabolism and nutrition disorders
Other adverse events (61 terms — click to expand)

ReactionSystemPhase I Dose Level 1: KHAD…Phase I Dose Level 2: KHAD…
FatigueGeneral disorders
Back, painMusculoskeletal and connective tissue disorders
AST, SGOTInvestigations
Cardiac-otherCardiac disorders
CoughRespiratory, thoracic and mediastinal disorders
Diarrhea w/o prior colostomyGastrointestinal disorders
Dry skinSkin and subcutaneous tissue disorders
Edema limbGeneral disorders
HypertensionVascular disorders
Joint, painMusculoskeletal and connective tissue disorders
Pain-otherGeneral disorders
Skin-otherSkin and subcutaneous tissue disorders
VomitingGastrointestinal disorders
ALT, SGPTInvestigations
AmylaseInvestigations
AnorexiaMetabolism and nutrition disorders
Chest wall, painMusculoskeletal and connective tissue disorders
ConstipationGastrointestinal disorders
CreatinineInvestigations
DehydrationMetabolism and nutrition disorders
Dry mouthGastrointestinal disorders
DyspepsiaGastrointestinal disorders
DyspneaRespiratory, thoracic and mediastinal disorders
Endocrine-otherEndocrine disorders
Erythema multiformeSkin and subcutaneous tissue disorders
Extremity-limb, painMusculoskeletal and connective tissue disorders
Fever w/o neutropeniaGeneral disorders
FlatulenceGastrointestinal disorders
GI-otherGastrointestinal disorders
HemoglobinBlood and lymphatic system disorders
Hot flashesVascular disorders
HyperglycemiaMetabolism and nutrition disorders
HyperkalemiaMetabolism and nutrition disorders
Incontinence, analGastrointestinal disorders
Infection Gr0-2 neut, urinary tractInfections and infestations
Infection w/ gr3-4 neut, urinary tractInfections and infestations
Infection w/ unk ANC ungual (nails)Infections and infestations
InsomniaPsychiatric disorders
Lip, painGastrointestinal disorders
LipaseInvestigations

Most-reported serious reactions: Cardiac-other, Hypophosphatemia.

Data from ClinicalTrials.gov NCT00953576 adverse events section.

Sponsor's own description

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.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Molecular pathways and targets in prostate cancer.
    Shtivelman E, Beer TM, Evans CP. · · 2014 · cited 81× · PMID 25277175 · DOI 10.18632/oncotarget.2406
  2. Repurposing non-oncology small-molecule drugs to improve cancer therapy: Current situation and future directions.
    Fu L, Jin W, Zhang J, Zhu L, et al · · 2022 · cited 47× · PMID 35256933 · DOI 10.1016/j.apsb.2021.09.006
  3. Agri-Food By-Products in Cancer: New Targets and Strategies.
    Sorrentino C, Di Gisi M, Gentile G, Licitra F, et al · · 2022 · cited 12× · PMID 36428610 · DOI 10.3390/cancers14225517

Verify or expand the search:

Other trials of ketoconazole

Trials testing the same drug.

Other recruiting trials for Prostate Cancer

Currently open trials in the same condition.

Other Dana-Farber Cancer Institute trials

Trials by the same sponsor.

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