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

Puma Biotechnology

Status and phase: Completed; Phase 1

Conditions: Malignant Carcinoma; Neoplasms

Treatments: Drug: Neratinib; Drug: Temsirolimus

Study type: Interventional

Funder types: Industry

Identifiers

NCT00838539

3144A1-2205 / B1891016

Details and patient eligibility

About

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.

Enrollment: 63 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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.

Exclusion criteria

• 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 design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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63 participants in 12 patient groups

Neratinib and Temsirolimus (Dose level 1)

Experimental group

Description:

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

Treatment:

Drug: Temsirolimus

Drug: Neratinib

Neratinib and Temsirolimus (Dose level 2)

Experimental group

Description:

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

Treatment:

Drug: Temsirolimus

Drug: Neratinib

Neratinib and Temsirolimus (Dose level 3)

Experimental group

Description:

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

Treatment:

Drug: Temsirolimus

Drug: Neratinib

Neratinib and Temsirolimus (Dose level 4)

Experimental group

Description:

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

Treatment:

Drug: Temsirolimus

Drug: Neratinib

Neratinib and Temsirolimus (Dose level 5)

Experimental group

Description:

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

Treatment:

Drug: Temsirolimus

Drug: Neratinib

Neratinib and Temsirolimus (Dose level 6)

Experimental group

Description:

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

Treatment:

Drug: Temsirolimus

Drug: Neratinib

Neratinib and Temsirolimus (Dose level 7)

Experimental group

Description:

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

Treatment:

Drug: Temsirolimus

Drug: Neratinib

Neratinib and Temsirolimus (Dose level 8)

Experimental group

Description:

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

Treatment:

Drug: Temsirolimus

Drug: Neratinib

Neratinib and Temsirolimus (Dose level 9)

Experimental group

Description:

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

Treatment:

Drug: Temsirolimus

Drug: Neratinib

Neratinib and Temsirolimus (Dose level 10)

Experimental group

Description:

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

Treatment:

Drug: Temsirolimus

Drug: Neratinib

Neratinib and Temsirolimus (Dose level 11)

Experimental group

Description:

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

Treatment:

Drug: Temsirolimus

Drug: Neratinib

Neratinib and Temsirolimus (Dose level 12)

Experimental group

Description:

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

Treatment:

Drug: Temsirolimus

Drug: Neratinib