Investigation of Tipifarnib in Treatment of Subjects With PTCL That Have Not Responded to Standard Therapy.

Sponsor

Kura Oncology, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT02464228

Collaborator

(none)

Enrollment

Locations

Arm

65.5

Actual Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Phase II study designed to investigate antitumor activity in terms of objective response rate (ORR) of tipifarnib subjects with advanced Peripheral T-Cell Lymphoma (PTCL). Tipifarnib will be administered orally until disease progression.

Condition or Disease	Intervention/Treatment	Phase
Relapsed or Refractory Peripheral T-Cell Lymphoma	Drug: Tipifarnib	Phase 2

Detailed Description

This Phase II study will investigate the antitumor activity in terms of ORR of tipifarnib in subjects with relapsed or refractory PTCL. The first 18 subjects may be of the following PTCL sub-types: PTCL not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), ALK-positive and negative anaplastic large cell lymphoma (ALCL), hepatosplenic T-cell lymphoma, enteropathy-associate T-cell lymphoma (EATL), extranodal natural killer (NK) T-cell lymphoma, nasal type and subcutaneous panniculitis-like T-cell lymphoma. The AITL expansion cohort (N=32) will enroll only subjects with AITL. An additional cohort of patients (N=12) expressing the wild type CXCL12 3' UTR will be enrolled in order to explore the benefits of tipifarnib treatment observed in patients having an absence of this gene variation or single nucleotide variation (SNV).

Tumor response assessments will be conducted according to Lugano Classification and/or mSWAT criteria.

Tumor assessments will be performed approximately every 8 weeks (cycles 2-6) and at least once approximately every 12 weeks thereafter (Cycles 9, 12, 15, etc.), and will continue until disease progression. Subjects experiencing a complete response may be considered for bone marrow transplantation. Upon disease progression, all subjects will be followed for survival and the use of subsequent therapy. All subjects will be followed for safety during treatment and up to approximately 30 days after treatment discontinuation or until before the initiation of another anti-cancer therapy. Additional follow up may be implemented until the subject recovers from any emergent treatment related toxicity or the adverse event is considered irreversible by the investigator.

Study Design

Study Type:

Interventional

Actual Enrollment :

65 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

An Open Label Phase II Study of Tipifarnib in Subjects With Relapsed or Refractory Peripheral T-Cell Lymphoma

Actual Study Start Date :

Oct 8, 2015

Actual Primary Completion Date :

Mar 24, 2021

Actual Study Completion Date :

Mar 24, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tipifarnib tipifarnib, oral	Drug: Tipifarnib oral Other Names: Zarnesta

Arm

Intervention/Treatment

Experimental: Tipifarnib

tipifarnib, oral

Drug: Tipifarnib

oral

Other Names:

Zarnesta

Outcome Measures

Primary Outcome Measures

Objective response rate (ORR) [2 years]
Response assessments according to Lugano Classification and/or mSWAT

Secondary Outcome Measures

Progression Free Survival [2 years]
To determine the antitumor activity in terms of PFS in subjects with relapsed/refractory PTCL
Duration of Response [1 year]
To determine the antitumor activity in terms of DOR in subjects with relapsed/refractory PTCL
Number of patients that experience Adverse Events (AEs) [Until 30 days following end of study]
To evaluate the safety and tolerability of tipifarnib in subjects with relapsed/refractory PTCL

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Diagnosis of PTCL according to the most recent edition of the World Health Organization (WHO) Classification of Tumors of Hematopoietic or Lymphoid Tissues, as follows:
Anaplastic large cell lymphoma (ALCL), ALK positive
ALCL, ALK negative
Angioimmunoblastic T-cell lymphoma (AITL)
Enteropathy-associated T-cell lymphoma
Extranodal natural killer (NK) T-cell lymphoma, nasal type
Hepatosplenic T-cell lymphoma
Peripheral T-cell lymphoma, not otherwise specified (NOS)
Subcutaneous panniculitis-like T-cell lymphoma
For enrollment into the AITL expansion cohort, subjects must have the diagnosis of AITL, nodal PTCL with T-follicular helper phenotype or follicular PTC.
For enrollment into the CXCL12+ PTCL expansion cohort, subjects must have the diagnosis of PTCL (a - h subtypes listed above, except AITL), consent to provide buccal swabs for CXCL12 SNP testing, and be found to be CXCL12+ based on testing by a Sponsor approved methodology.
Relapsed or are refractory to at least 1 prior systemic cytotoxic therapy. -Subjects must have received conventional therapy as a prior therapy.
Subject has consented to provide at least 6 unstained tumor slides (10 preferred) or an FFPE block for biomarker testing.
Subject has measurable disease as determined by the Lugano Classification and/or mSWAT.
At least 2 weeks since the last systemic therapy regimen prior to enrollment.
At least 2 weeks since last radiotherapy if radiation was localized to the only site of measurable disease, unless there is documentation of disease progression of the irradiated site. Subjects must have recovered from all acute toxicities from radiotherapy.
ECOG performance status of 0-2
Acceptable liver and renal function
Acceptable hematologic status
Female subjects must be either:
Of non-child-bearing potential (surgically sterilized or at least 2 years post- menopausal); or
If of child-bearing potential, subject must use an adequate method of contraception consisting of two-barrier method or one barrier method with a spermicide or intrauterine device. Both females and male subjects with female partners of child- bearing potential must agree to use an adequate method of contraception for 2 weeks prior to screening, during, and at least 4 weeks after last dose of trial medication. Female subjects must have a negative serum or urine pregnancy test within 72 hours prior to start of trial medication.
Not breast feeding at any time during the study.
Written and voluntary informed consent.

Exclusion Criteria:

Diagnosis of any of the following:
Precursor T-cell lymphoma or leukemia
Adult T-cell lymphoma/leukemia (ATLL)
T-cell prolymphocytic leukemia
T-cell large granular lymphocytic leukemia
Primary cutaneous type anaplastic large cell lymphoma
Mycosis fungoide/Sezary syndrome
Ongoing treatment with an anticancer agent not contemplated in this protocol.
Prior treatment (at least 1 full treatment cycle) with an FTase inhibitor.
Any history of clinically relevant coronary artery disease or myocardial infarction within the last 3 years.
Known central nervous system lymphoma.
Stem cell transplant less than 3 months prior to enrolment.
Non-tolerable > Grade 2 neuropathy or evidence of unstable neurological symptoms within 4 weeks of Cycle 1 Day 1.
Major surgery, other than diagnostic surgery, within 2 weeks prior to Cycle 1 Day 1, without complete recovery.
Other active malignancy requiring therapy such as radiation, chemotherapy, or immunotherapy.
Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy.

Known infection with HIV, or an active infection with hepatitis B or hepatitis C.

Subjects who have exhibited allergic reactions to tipifarnib, or structural compounds similar to tipifarnib or to its excipients. This includes hypersensitivity to imidazoles, such as clotrimazole, ketoconazole, miconazole and others in this drug class.
Concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study.
The subject has legal incapacity or limited legal capacity.
Dementia or significantly altered mental status that would limit the understanding or rendering of informed consent and compliance with the requirements of this protocol.
Unwillingness or inability to comply with the study protocol for any reason.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University Medical Center	Palo Alto	California	United States	94305
2	Yale University, Yale Cancer Center	New Haven	Connecticut	United States	06520
3	H. Lee Moffitt Cancer Center & Research Institute, Inc.	Tampa	Florida	United States	33612
4	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
5	Mayo Clinic	Rochester	Minnesota	United States	55905
6	Samsung Medical Center	Seoul		Korea, Republic of	06351
7	Hospital Universitari Vall d'Hebron	Barcelona		Spain	08035
8	Institut Catala d'Oncologia de Girona	Girona		Spain	17007
9	MD Anderson Cancer Center Madrid	Madrid		Spain	28033
10	Hospital Universitario 12 Octubre de Madrid	Madrid		Spain	28041
11	Hospital Universitario de Salamanca	Salamanca		Spain	37007
12	Hospital Universitario Virgen del Rocio	Sevilla		Spain	41013
13	Hospital Clinico Universitario de Valencia	Valencia		Spain	46010