NeoplasmsPhase 1NCT00838539

Study Evaluating Neratinib In Combination With Temsirolimus In Subjects With Solid Tumors

A Phase 1 study testing Neratinib and Temsirolimus in people with Neoplasms and Malignant Carcinoma, run by Puma Biotechnology, Inc. at 5 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The primary purpose of this study is to identify the maximum tolerated dose(s) (MTD) of neratinib in combination with temsirolimus in subjects with solid tumors. This study will also include a preliminary evaluation of efficacy, and assessment of pharmacokinetic (PK) parameters of the combination. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Neoplasms, Malignant Carcinoma
What is being tested?: Neratinib and Temsirolimus
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 63 participants
Where: 5 sitesin 2 countries
Study dates: Apr 2009to Dec 2013
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Pathologic diagnosis of advanced or metastatic solid tumor.
Measurable disease per Response Criteria in Solid Tumors (RECIST criteria).
Incurable cancer, with disease progression following at least 1 conventional or standard therapy for locally advanced or metastatic disease.
Negative pregnancy test for women of child bearing potential.

Who cannot join

Chronic treatment with corticosteroids.
Primary central nervous system (CNS) tumors and active metastases.
Presence of clinically significant or uncontrolled cardiac disease.
Significant chronic or recent acute gastrointestinal disorder with diarrhea as a major symptom.
Symptomatic or prior history of non-infectious interstitial pneumonitis.

Trial locations and contacts

5 sites in 2 countries.

Country

City, postcode or hospital

5 sites in 2 countries

United States4 sites

Massachusetts General Hospital
Boston, Massachusetts, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02115
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Dana Farber Cancer Institute
Boston, Massachusetts, 02215

Other trials in United States

France1 site

Institut Gustave Roussy
Villejuif, 94805

Other trials in France

About this study

Official title: A Phase 1 Study Of Neratinib In Combination With Temsirolimus In Subjects With Solid Tumors

Conditions: Neoplasms, Malignant Carcinoma
Being tested: Neratinib, Temsirolimus
Keywords: Neratinib, solid tumors, phase 1, dose finding study, HKI-272, Nerlynx, Temsirolimus, PB-272
Medical subject headings: Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

NeratinibDrug
Also called HKI-272
TemsirolimusDrug
Also called Torisel, CCI-779

Study groups in NCT00838539
Study group	Role	What they receive
Neratinib and Temsirolimus (Dose level 1)	Experimental	Neratinib 120 mg and Temsirolimus 15 mg: Neratinib 40 mg tablets administered orally daily for as long as tolerated and the disease under study does not worsen. Temsirolimus administered intravenously once weekly for as long as tolerated and the disease under study does not worsen Receives: Drug: Neratinib; Drug: Temsirolimus
Neratinib and Temsirolimus (Dose level 2)	Experimental	Neratinib 120 mg and Temsirolimus 25 mg: Neratinib 40 mg tablets administered orally daily for as long as tolerated and the disease under study does not worsen. Temsirolimus administered intravenously once weekly for as long as tolerated and the disease under study does not worsen Receives: Drug: Neratinib; Drug: Temsirolimus
Neratinib and Temsirolimus (Dose level 3)	Experimental	Neratinib 120 mg and Temsirolimus 50 mg: Neratinib 40 mg tablets administered orally daily for as long as tolerated and the disease under study does not worsen. Temsirolimus administered intravenously once weekly for as long as tolerated and the disease under study does not worsen Receives: Drug: Neratinib; Drug: Temsirolimus
Neratinib and Temsirolimus (Dose level 4)	Experimental	Neratinib 120 mg and Temsirolimus 75 mg: Neratinib 40 mg tablets administered orally daily for as long as tolerated and the disease under study does not worsen. Temsirolimus administered intravenously once weekly for as long as tolerated and the disease under study does not worsen Receives: Drug: Neratinib; Drug: Temsirolimus
Neratinib and Temsirolimus (Dose level 5)	Experimental	Neratinib 160 mg and Temsirolimus 15 mg: Neratinib 40 mg tablets administered orally daily for as long as tolerated and the disease under study does not worsen. Temsirolimus administered intravenously once weekly for as long as tolerated and the disease under study does not worsen Receives: Drug: Neratinib; Drug: Temsirolimus
Neratinib and Temsirolimus (Dose level 6)	Experimental	Neratinib 160 mg and Temsirolimus 25 mg: Neratinib 40 mg tablets administered orally daily for as long as tolerated and the disease under study does not worsen. Temsirolimus administered intravenously once weekly for as long as tolerated and the disease under study does not worsen Receives: Drug: Neratinib; Drug: Temsirolimus
Neratinib and Temsirolimus (Dose level 7)	Experimental	Neratinib 160 mg and Temsirolimus 50 mg: Neratinib 40 mg tablets administered orally daily for as long as tolerated and the disease under study does not worsen. Temsirolimus administered intravenously once weekly for as long as tolerated and the disease under study does not worsen Receives: Drug: Neratinib; Drug: Temsirolimus
Neratinib and Temsirolimus (Dose level 8)	Experimental	Neratinib 160 mg and Temsirolimus 75 mg: Neratinib 40 mg tablets administered orally daily for as long as tolerated and the disease under study does not worsen. Temsirolimus administered intravenously once weekly for as long as tolerated and the disease under study does not worsen Receives: Drug: Neratinib; Drug: Temsirolimus
Neratinib and Temsirolimus (Dose level 9)	Experimental	Neratinib 200 mg and Temsirolimus 15 mg: Neratinib 40 mg tablets administered orally daily for as long as tolerated and the disease under study does not worsen. Temsirolimus administered intravenously once weekly for as long as tolerated and the disease under study does not worsen Receives: Drug: Neratinib; Drug: Temsirolimus
Neratinib and Temsirolimus (Dose level 10)	Experimental	Neratinib 200 mg and Temsirolimus 25 mg: Neratinib 40 mg tablets administered orally daily for as long as tolerated and the disease under study does not worsen. Temsirolimus administered intravenously once weekly for as long as tolerated and the disease under study does not worsen Receives: Drug: Neratinib; Drug: Temsirolimus
Neratinib and Temsirolimus (Dose level 11)	Experimental	Neratinib 200 mg and Temsirolimus 50 mg: Neratinib 40 mg tablets administered orally daily for as long as tolerated and the disease under study does not worsen. Temsirolimus administered intravenously once weekly for as long as tolerated and the disease under study does not worsen Receives: Drug: Neratinib; Drug: Temsirolimus
Neratinib and Temsirolimus (Dose level 12)	Experimental	Neratinib 240 mg and Temsirolimus 15 mg: Neratinib 40 mg tablets administered orally daily for as long as tolerated and the disease under study does not worsen. Temsirolimus administered intravenously once weekly for as long as tolerated and the disease under study does not worsen Receives: Drug: Neratinib; Drug: Temsirolimus

What is being measured

The primary outcome is the main question the study is designed to answer.

Probability of Dose-Limiting Toxicity (DLT)
A DLT was defined as any dose-limiting Adverse Event related to neratinib + Temsirolimus as Grade 3 or higher nonhematologic toxicity (except neutropenia) or Grade 3 or higher diarrhea lasting >2 days with optimal antidiarrheal therapy etc.
Measured: From first dose date to day 28
Maximum Tolerated Dose (MTD) of Neratinib in Combination With Temsirolimus
Identification of the daily neratinib high-dose MTD in combination with weekly temsirolimus.
Measured: From first dose date to day 28
Maximum Tolerated Dose (MTD) of Temsirolimus in Combination With Neratinib
Identification of the weekly temsirolimus high-dose MTD in combination with daily neratinib
Measured: From first dose date to day 28
Adverse Events Causing Dose Limiting Toxicities
A DLT was defined as any dose-limiting adverse event (AE) related to neratinib + TEMSR as follows: [1] Grade 3 or 4 nonhematologic toxicity (Grade 3 or 4 nausea, vomiting, hyperglycemia, hypophosphatemia, hypertriglyceridemia, or hypercholesterolemia was not considered a DLT unless the subject was already receiving optimal medical therapy). [2] Grade 3 or 4 diarrhea lasting >2 days while subject was on optimal vigorous antidiarrheal therapy.
[3] Grade 4 neutropenia lasting >3 days or Grade 3 or 4 neutropenia of any duration with sepsis or a fever >38.5C. [4] Platelet value less than or equal to 25,000/mm3 or bleeding requiring a platelet transfusion. [5] Delayed recovery from toxicity, which delayed rescheduled re-treatment for >3 weeks. [6] Inability to maintain the original dose during the first 28 days of treatment (at least 21 doses of neratinib and 2 doses of TEMSR at the original specified dose) due to treatment-related toxicity.
Measured: From first dose date to day 21

Secondary outcomes (4)

Best Overall Response
The best overall response was described using the data as reported by study center investigators 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. Progression is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Measured: From first dose date to progression/death or last tumor assessment, up to 30 months
Clinical Benefit Rate
Percentage of subjects with a complete response, partial response, or stable disease >= 24 weeks, as determined by investigator assessment 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. Progression is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Measured: From first dose date to progression/death or last tumor assessment, up to 30 months
Objective Response Rate
Percentage of subjects with a complete response (CR) or partial response (PR) 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. Progression is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Measured: From first dose date to progression/death or last tumor assessment, up to 30 months
Area Under the Curve Tau
Area Under the Curve tau of neratinib concentrations, collected at 2, 4, 8, and 24 hours post-neratinib administration, at the week 4 dose.
Measured: Week 4

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Apr 2009Dec 2013

First posted6 Feb 2009 (estimated)
Study startApr 2009
Primary completionJun 2011
Study completionDec 2013

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for NeoplasmsStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Enrolment: 63 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00838539
Sponsor's protocol ID: 3144A1-2205 / B1891016
Status last verified: Aug 2018
First submitted: 5 Feb 2009
Last updated: 18 Sep 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

Gandhi L, Bahleda R, Tolaney SM, Kwak EL, Cleary JM, Pandya SS, Hollebecque A, Abbas R, Ananthakrishnan R, Berkenblit A, Krygowski M, Liang Y, Turnbull KW, Shapiro GI, Soria JC. Phase I study of neratinib in combination with temsirolimus in patients with human epidermal growth factor receptor 2-dependent and other solid tumors. J Clin Oncol. 2014 Jan 10;32(2):68-75. doi: 10.1200/JCO.2012.47.2787. Epub 2013 Dec 9.
PubMed 24323026

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 18 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1 Study Of Neratinib In Combination With Temsirolimus In Subjects With Solid Tumors
ClinicalTrials.gov ID: NCT00838539
Acronym / sponsor ID: 3144A1-2205 / B1891016
Conditions: Neoplasms, Malignant Carcinoma
Keywords: Neratinib, solid tumors, phase 1, dose finding study, HKI-272, Nerlynx, Temsirolimus, PB-272
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 63 participants (actual)
Lead sponsor: Puma Biotechnology, Inc.Industry (pharma, biotech, devices)
Study start: Apr 2009 (actual)
Primary completion: Jun 2011 (actual)
Study completion: Dec 2013 (actual)
First posted: 6 Feb 2009 (estimated)
Results: Posted 26 Feb 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 12

Arm	Type	Receives
Neratinib and Temsirolimus (Dose level 1)	Experimental	Drug: Neratinib, Drug: TemsirolimusNeratinib 120 mg and Temsirolimus 15 mg: Neratinib 40 mg tablets administered orally daily for as long as tolerated and the disease under study does not worsen. Temsirolimus administered intravenously once weekly for as long as tolerated and the disease under study does not worsen
Neratinib and Temsirolimus (Dose level 2)	Experimental	Drug: Neratinib, Drug: TemsirolimusNeratinib 120 mg and Temsirolimus 25 mg: Neratinib 40 mg tablets administered orally daily for as long as tolerated and the disease under study does not worsen. Temsirolimus administered intravenously once weekly for as long as tolerated and the disease under study does not worsen
Neratinib and Temsirolimus (Dose level 3)	Experimental	Drug: Neratinib, Drug: TemsirolimusNeratinib 120 mg and Temsirolimus 50 mg: Neratinib 40 mg tablets administered orally daily for as long as tolerated and the disease under study does not worsen. Temsirolimus administered intravenously once weekly for as long as tolerated and the disease under study does not worsen
Neratinib and Temsirolimus (Dose level 4)	Experimental	Drug: Neratinib, Drug: TemsirolimusNeratinib 120 mg and Temsirolimus 75 mg: Neratinib 40 mg tablets administered orally daily for as long as tolerated and the disease under study does not worsen. Temsirolimus administered intravenously once weekly for as long as tolerated and the disease under study does not worsen
Neratinib and Temsirolimus (Dose level 5)	Experimental	Drug: Neratinib, Drug: TemsirolimusNeratinib 160 mg and Temsirolimus 15 mg: Neratinib 40 mg tablets administered orally daily for as long as tolerated and the disease under study does not worsen. Temsirolimus administered intravenously once weekly for as long as tolerated and the disease under study does not worsen
Neratinib and Temsirolimus (Dose level 6)	Experimental	Drug: Neratinib, Drug: TemsirolimusNeratinib 160 mg and Temsirolimus 25 mg: Neratinib 40 mg tablets administered orally daily for as long as tolerated and the disease under study does not worsen. Temsirolimus administered intravenously once weekly for as long as tolerated and the disease under study does not worsen
Neratinib and Temsirolimus (Dose level 7)	Experimental	Drug: Neratinib, Drug: TemsirolimusNeratinib 160 mg and Temsirolimus 50 mg: Neratinib 40 mg tablets administered orally daily for as long as tolerated and the disease under study does not worsen. Temsirolimus administered intravenously once weekly for as long as tolerated and the disease under study does not worsen
Neratinib and Temsirolimus (Dose level 8)	Experimental	Drug: Neratinib, Drug: TemsirolimusNeratinib 160 mg and Temsirolimus 75 mg: Neratinib 40 mg tablets administered orally daily for as long as tolerated and the disease under study does not worsen. Temsirolimus administered intravenously once weekly for as long as tolerated and the disease under study does not worsen
Neratinib and Temsirolimus (Dose level 9)	Experimental	Drug: Neratinib, Drug: TemsirolimusNeratinib 200 mg and Temsirolimus 15 mg: Neratinib 40 mg tablets administered orally daily for as long as tolerated and the disease under study does not worsen. Temsirolimus administered intravenously once weekly for as long as tolerated and the disease under study does not worsen
Neratinib and Temsirolimus (Dose level 10)	Experimental	Drug: Neratinib, Drug: TemsirolimusNeratinib 200 mg and Temsirolimus 25 mg: Neratinib 40 mg tablets administered orally daily for as long as tolerated and the disease under study does not worsen. Temsirolimus administered intravenously once weekly for as long as tolerated and the disease under study does not worsen
Neratinib and Temsirolimus (Dose level 11)	Experimental	Drug: Neratinib, Drug: TemsirolimusNeratinib 200 mg and Temsirolimus 50 mg: Neratinib 40 mg tablets administered orally daily for as long as tolerated and the disease under study does not worsen. Temsirolimus administered intravenously once weekly for as long as tolerated and the disease under study does not worsen
Neratinib and Temsirolimus (Dose level 12)	Experimental	Drug: Neratinib, Drug: TemsirolimusNeratinib 240 mg and Temsirolimus 15 mg: Neratinib 40 mg tablets administered orally daily for as long as tolerated and the disease under study does not worsen. Temsirolimus administered intravenously once weekly for as long as tolerated and the disease under study does not worsen

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

Pathologic diagnosis of advanced or metastatic solid tumor.
Measurable disease per Response Criteria in Solid Tumors (RECIST criteria).
Incurable cancer, with disease progression following at least 1 conventional or standard therapy for locally advanced or metastatic disease.
Negative pregnancy test for women of child bearing potential.

Key exclusion criteria (5 listed)

Chronic treatment with corticosteroids.
Primary central nervous system (CNS) tumors and active metastases.
Presence of clinically significant or uncontrolled cardiac disease.
Significant chronic or recent acute gastrointestinal disorder with diarrhea as a major symptom.
Symptomatic or prior history of non-infectious interstitial pneumonitis.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
NeratinibAlso: HKI-272	Drug	Neratinib and Temsirolimus (Dose level 1), Neratinib and Temsirolimus (Dose level 10), Neratinib and Temsirolimus (Dose level 11), Neratinib and Temsirolimus (Dose level 12), Neratinib and Temsirolimus (Dose level 2), Neratinib and Temsirolimus (Dose level 3), Neratinib and Temsirolimus (Dose level 4), Neratinib and Temsirolimus (Dose level 5), Neratinib and Temsirolimus (Dose level 6), Neratinib and Temsirolimus (Dose level 7), Neratinib and Temsirolimus (Dose level 8), Neratinib and Temsirolimus (Dose level 9)
TemsirolimusAlso: Torisel, CCI-779	Drug	Neratinib and Temsirolimus (Dose level 1), Neratinib and Temsirolimus (Dose level 10), Neratinib and Temsirolimus (Dose level 11), Neratinib and Temsirolimus (Dose level 12), Neratinib and Temsirolimus (Dose level 2), Neratinib and Temsirolimus (Dose level 3), Neratinib and Temsirolimus (Dose level 4), Neratinib and Temsirolimus (Dose level 5), Neratinib and Temsirolimus (Dose level 6), Neratinib and Temsirolimus (Dose level 7), Neratinib and Temsirolimus (Dose level 8), Neratinib and Temsirolimus (Dose level 9)

Primary outcome

Probability of Dose-Limiting Toxicity (DLT)
Time frame: From first dose date to day 28
A DLT was defined as any dose-limiting Adverse Event related to neratinib + Temsirolimus as Grade 3 or higher nonhematologic toxicity (except neutropenia) or Grade 3 or higher diarrhea lasting >2 days with optimal antidiarrheal therapy etc.
Maximum Tolerated Dose (MTD) of Neratinib in Combination With Temsirolimus
Time frame: From first dose date to day 28
Identification of the daily neratinib high-dose MTD in combination with weekly temsirolimus.
Maximum Tolerated Dose (MTD) of Temsirolimus in Combination With Neratinib
Time frame: From first dose date to day 28
Identification of the weekly temsirolimus high-dose MTD in combination with daily neratinib
Adverse Events Causing Dose Limiting Toxicities
Time frame: From first dose date to day 21
A DLT was defined as any dose-limiting adverse event (AE) related to neratinib + TEMSR as follows: [1] Grade 3 or 4 nonhematologic toxicity (Grade 3 or 4 nausea, vomiting, hyperglycemia, hypophosphatemia, hypertriglyceridemia, or hypercholesterolemia was not considered a DLT unless the subject was already receiving optimal medical therapy). [2] Grade 3 or 4 diarrhea lasting >2 days while subject was on optimal vigorous antidiarrheal therapy. [3] Grade 4 neutropenia lasting >3 days or Grade 3 or 4 neutropenia of any duration with sepsis or a fever >38.5C. [4] Platelet value less than or equal to 25,000/mm3 or bleeding requiring a platelet transfusion. [5] Delayed recovery from toxicity, which delayed rescheduled re-treatment for >3 weeks. [6] Inability to maintain the original dose during the first 28 days of treatment (at least 21 doses of neratinib and 2 doses of TEMSR at the original specified dose) due to treatment-related toxicity.

4 secondary outcomes

Best Overall Response
Time frame: From first dose date to progression/death or last tumor assessment, up to 30 months
Clinical Benefit Rate
Time frame: From first dose date to progression/death or last tumor assessment, up to 30 months
Objective Response Rate
Time frame: From first dose date to progression/death or last tumor assessment, up to 30 months
Area Under the Curve Tau
Time frame: Week 4

Results and safety

Results posted to the registry on 26 Feb 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
N120 + T15	3	0
N120 + T25	6	0
N120 + T50	5	0
N120 + T75	4	0
N160 + T15	6	0
N160 + T25	4	0
N160 + T50	7	2
N160 + T75	6	0
N200 + T15	5	0
N200 + T25	8	0
N200 + T50	5	0
N240 + T15	4	0

Primary outcome: Probability of Dose-Limiting Toxicity (DLT)

Time frame: From first dose date to day 28. Number. Unit: percent probability

Measure	Neratinib 120 mg n = 14	Neratinib 160 mg n = 20	Neratinib 200 mg n = 13	Neratinib 240 mg n = 4
Temsirolimus 15 mg	0	12.5	12.5	50
Temsirolimus 25 mg	13.63	13.64	12.5	–
Temsirolimus 50 mg	13.63	13.64	100	–
Temsirolimus 75 mg	13.63	50	–	–

Population analysed: Evaluable subjects for the Maximum Tolerated Dose (MTD) contour estimation were those who either experienced a DLT within the first 28 days, regardless of the number of doses of treatment received, or received at least 21 doses of neratinib and at least 2 doses of Temsirolimus in the first 28 days of treatment.

Primary outcome: Maximum Tolerated Dose (MTD) of Neratinib in Combination With Temsirolimus

Time frame: From first dose date to day 28. Number. Unit: mg

Measure	MTD Ner With TEMS n = 51
Value	200

Population analysed: Evaluable subjects were those that either experienced a dose limiting toxicity within the first 28 days, regardless of the number of doses of treatment received, or those that received at least 21 doses of neratinib and at least 2 doses of Temsirolimus in the first 28 days of treatment at the original dose level prescribed.

Primary outcome: Maximum Tolerated Dose (MTD) of Temsirolimus in Combination With Neratinib

Time frame: From first dose date to day 28. Number. Unit: mg

Measure	MTD TEMS With Ner n = 51
Value	50

Population analysed: Evaluable subjects include those that either experienced a dose limiting toxicity within the first 28 days, regardless of the number of doses of treatment received, or those that received at least 21 doses of neratinib and at least 2 doses of Temsirolimus in the first 28 days of treatment at the original dose level prescribed.

Primary outcome: Adverse Events Causing Dose Limiting Toxicities

Time frame: From first dose date to day 21. Count of participants. Unit: Participants

Measure	N120 + T15 n = 3	N120 + T25 n = 5	N120 + T50 n = 5	N120 + T75 n = 4	N160 + T15 n = 4	N160 + T25 n = 4	N160 + T50 n = 7	N160 + T75 n = 6	N200 + T15 n = 5	N200 + T25 n = 8	N200 + T50 n = 5	N240 + T15 n = 4
Value	0	1	1	0	1	1	0	3	0	1	1	2

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: From first dose through 28 days after last dose, up to 30 months.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
N120 + T15	1 of 3 (33.3%)	3 of 3 (100%)	Not reported
N120 + T25	2 of 6 (33.3%)	5 of 6 (83.3%)	Not reported
N120 + T50	1 of 5 (20%)	5 of 5 (100%)	Not reported
N120 + T75	1 of 4 (25%)	4 of 4 (100%)	Not reported
N160 + T15	3 of 6 (50%)	4 of 6 (66.7%)	Not reported
N160 + T25	2 of 4 (50%)	4 of 4 (100%)	Not reported
N160 + T50	5 of 7 (71.4%)	7 of 7 (100%)	Not reported
N160 + T75	3 of 6 (50%)	6 of 6 (100%)	Not reported
N200 + T15	4 of 5 (80%)	5 of 5 (100%)	Not reported
N200 + T25	5 of 8 (62.5%)	8 of 8 (100%)	Not reported
N200 + T50	3 of 5 (60%)	5 of 5 (100%)	Not reported
N240 + T15	3 of 4 (75%)	4 of 4 (100%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 24323026Gandhi L, Bahleda R, Tolaney SM, Kwak EL, Cleary JM, Pandya SS, Hollebecque A, Abbas R, Ananthakrishnan R, Berkenblit A, Krygowski M, Liang Y, Turnbull KW, Shapiro GI, Soria JC. Phase I study of neratinib in combination with temsirolimus in patients with human epidermal growth factor receptor 2-dependent and other solid tumors. J Clin Oncol. 2014 Jan 10;32(2):68-75. doi: 10.1200/JCO.2012.47.2787. Epub 2013 Dec 9.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Puma study director

Biotechnology

5 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Neratinib and Temsirolimus in people with Neoplasms and Malignant Carcinoma, run by Puma Biotechnology, Inc. at 5 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States, France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Feb 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Probability of Dose-Limiting Toxicity (DLT) (time frame: From first dose date to day 28). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00838539, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Sep 2018.