A Phase Ib Study of the Safety, Tolerability and Efficacy of LY2780301 in Combination With Gemcitabine

NCT ID: NCT02018874

Last Updated: 2016-07-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 52 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-09-30
• Study Completion Date: 2016-04-30

Brief Summary

In the First-in-Human, JWAA trial, the LY2780301 displayed a favourable safety profile, a high pharmacokinetic exposure and the ability to decrease pS6. LY2780301 has shown synergistic activity in combination with targeted agents or chemotherapy including gemcitabine. We propose herein to combine LY2780301 with gemcitabine and to treat different tumor types with molecular alterations. This may validate the anti-tumor activity of the LY2780301 and it will increase our knowledge regarding molecular predictors of its efficacy.

Conditions

Solid Tumors and Non-Hodgkin's Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

LY2780301

Group Type: EXPERIMENTAL

LY2780301

Intervention Type: DRUG

LY2780301 will be given orally Q.D. at different dose levels. Because of a favourable safety profile, the different dose levels will be as follow :

• Dose level -1: 300 mg Q.D.
• Dose level -0.5: 400 mg Q.D.
• Dose level 1: 400 mg Q.D.
• Dose level 1.5: 500 mg Q.D.
• Dose level 2 : 500 mg Q.D.

Gemcitabine

Intervention Type: DRUG

The dose level of Gemcitabine will be fixed (1000 mg/m2). Gemcitabine will be administered over a 30 minutes infusion.

Interventions

LY2780301

LY2780301 will be given orally Q.D. at different dose levels. Because of a favourable safety profile, the different dose levels will be as follow :

• Dose level -1: 300 mg Q.D.
• Dose level -0.5: 400 mg Q.D.
• Dose level 1: 400 mg Q.D.
• Dose level 1.5: 500 mg Q.D.
• Dose level 2 : 500 mg Q.D.

Intervention Type: DRUG

Gemcitabine

The dose level of Gemcitabine will be fixed (1000 mg/m2). Gemcitabine will be administered over a 30 minutes infusion.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Dose Escalation portion (Part 1): have histological or cytological evidence of a diagnosis of cancer that is advanced and/or metastatic disease (including Non-Hodgkin's Lymphoma) with selected molecular alterations and for which no proven effective therapy exists. ;

2. Dose Confirmation portion (Part 2): have histological or cytological evidence of cancer (solid tumor or Non-Hodgkin's Lymphoma) that is advanced and/or metastatic disease:

• Cohort A: Up to 20 patients of any histological type (solid tumor or Non-Hodgkin's Lymphoma) with selected molecular alterations
• Cohort B: Up to 12 patients with ovarian cancer and with selected molecular alterations 1.1 (Appendix 4) for solid tumors or by the Revised Response Criteria for Malignant Lymphoma

Dose Confirmation portion:

• Measurable disease as defined by RECIST 1.1 for solid tumors (Appendix 4) except ovarian cancer or
• Response Criteria for Patients with Ovarian Cancer Who Have Evaluable but Non-Measurable Disease (Appendix 5) or
• Revised Response Criteria for Non-Hodgkins Lymphoma (Appendix 6) [4] Are >/=18 years of age ; [5] Written informed consent ; [6] Have adequate organ function including:

• Hematologic: absolute neutrophil count (ANC) >/=1.5 x 109/L, platelets

>/=100 x 109/L, and hemoglobin >/=9 g/dL.

• Hepatic: bilirubin </=1.5 times upper limits of normal (ULN); alanine transaminase (ALT) and AST </=2.5 x ULN. (</=5 x ULN if the liver has tumor involvement).
• Renal: Serum creatinine </=1.5 x ULN or calculated creatinine clearance >45 ml/min (MDRD) [7] ECOG performance status </= 1 ; [8] Have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, cancer-related hormonal therapy, or other investigational therapy for at least 2 weeks (3 weeks for myelosuppressive agents) prior to study enrolment and all prior treatment related toxicities must be CTCAE (Version 4.0) </= Grade 1 (except alopecia) at the time of enrolment. Patients with prostate cancers progressing under LHRH agonist therapy, may have that treatment continued while receiving study drug ; [9] Males and females with reproductive potential must agree to use medically approved contraceptive precautions during the trial and for 6 months following the last dose of study drug ; [10] Females with childbearing potential must have had a negative serum pregnancy test </= 14 days prior to the first dose of study drug ; [11] Have an estimated life expectancy >/=12 weeks ; [12] Able to swallow and retain orally administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels ;

Exclusion Criteria

[13] Any serious and/or unstable pre-existing medical conditions, psychiatric disorder, or other conditions that could, in the opinion of the investigator, interfere with subject's safety, obtaining informed consent or compliance to the study procedures ; [14] Have symptomatic CNS malignancy or symptomatic brain metastasis. Patients with treated CNS metastases are eligible provided their disease is radiographically stable and asymptomatic and they are not currently receiving corticosteroids. Screening of asymptomatic patients without history of CNS metastasis is not required ; [15] Have pre-existing not controlled cardiovascular disease (including acute coronary syndromes, unstable angina, coronary angioplasty, or stenting within the past 6 months) or any QTc prolongation (defined as a QTc interval > 480 ms according to Friedericia's correction) or other significant ECG abnormalities including 2nd degree AV block type II, 3rd degree AV block, or bradycardia (HR < 50 bpm), or any history of 2nd or 3rd degree block ; [16] Concomitant treatment prohibited in section 7.8 ; [17] Pregnancy and Breast Feeding ;

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gustave Roussy, Cancer Campus, Grand Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jean Charles Soria, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Gustave Roussy, Cancer Campus, Grand Paris

Locations

Gustave Roussy

Villejuif, Val de Marne, France

Countries

France

References

Angevin E, Cassier PA, Italiano A, Goncalves A, Gazzah A, Terret C, Toulmonde M, Gravis G, Varga A, Parlavecchio C, Paci A, Poinsignon V, Soria JC, Drubay D, Hollebecque A. Safety, tolerability and antitumour activity of LY2780301 (p70S6K/AKT inhibitor) in combination with gemcitabine in molecularly selected patients with advanced or metastatic cancer: a phase IB dose escalation study. Eur J Cancer. 2017 Sep;83:194-202. doi: 10.1016/j.ejca.2017.06.036. Epub 2017 Jul 24.

Reference Type: DERIVED

PMID: 28750271 (View on PubMed)

Related Links

http://www.gustaveroussy.fr/fr/essai

Related Info

Other Identifiers

2013/1975

Identifier Type: OTHER

Identifier Source: secondary_id

2013-000671-33

Identifier Type: -

Identifier Source: org_study_id