A Randomized, Double Blind Study Evaluating Paclitaxel With and Without RAD001 in Patients With Gastric Carcinoma After Prior Chemotherapy

NCT01248403 | Completed Phase 3 DMC

• 1 other identifier: CRAD001RDE35T
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

Adult patients with gastric carcinoma which has progressed after initial treatment with a fluoropyrimidines-containing regimen will be treated with paclitaxel plus RAD001 or plus placebo. The hypothesis is that patients with RAD001 have significantly prolonged overall survival compared to patients who are treated with paclitaxel alone.

Conditions

Advanced Gastric Cancer; Esophagogastric Junction Cancer

Keywords

RAD001; Paclitaxel; gastric cancer; advanced gastric or esophagogastric junction cancer

Outcome Measures

Primary Outcomes (1)

• overall survival

  6 months follow-up

Secondary Outcomes (4)

• best overall response

  staging every 8 weeks

• progression-free survival

  staging every 8 weeks

• number of participants with adverse events as a measure of safety and tolerability

  every week until end of treatment

• disease control rate

  every 8 weeks

Study Arms (2)

paclitaxel + placebo

ACTIVE COMPARATOR

Paclitaxel 80 mg/m2 on day 1, day 8 and day 15 of every 28-day cycle. \+ Placebo (2 tablets / day) d1-d28

Drug: Paclitaxel

paclitaxel + RAD001

EXPERIMENTAL

Paclitaxel 80 mg/m2 on day 1, day 8 and day 15 of every 28-day cycle. \+ RAD001 10mg (2 x5 mg tablets / day) d1-d28

Drug: Paclitaxel; Drug: RAD001

Interventions

Paclitaxel DRUG

Paclitaxel 80 mg/m2 on day 1, day 8 and day 15 of every 28-day cycle.

paclitaxel + RAD001; paclitaxel + placebo

RAD001 DRUG

RAD001 10mg (2 x5 mg tablets / day) d1-d28

Also known as: Everolimus, Certican

paclitaxel + RAD001

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients ≥ 18 years old
• Histologically or cytologically confirmed and documented gastric adenocarcinoma. Adenocarcinomata of the gastro-esophageal junction will be allowed, if they have advanced disease (inoperable, recurrent or metastatic disease).
• Documented progressive disease during/after one, two or three prior treatments containing 5FU and/or its precursors or derivatives in the palliative setting
• At least one measurable or evaluable lesion by RECIST as determined by Computed Tomography (CT) Scan or Magnetic Resonance Imaging (MRI)
• ECOG performance status of 0, 1 or 2
• The following laboratory parameters:
• Absolute neutrophil count ≥ 1.5 x 109/L
• Platelets ≥ 100 x 109/L
• Hemoglobin (Hgb) ≥ 9 g/dL
• Serum creatinine ≤ 2 x Upper Limit of Normal (ULN)
• Adequate liver function:
• Total serum calcium (corrected for serum albumin) or ionized calcium ≥ LLN
• Women of childbearing potential must have a negative serum pregnancy test within 7 days of the first administration of study treatments and must be willing to use adequate methods of contraception during the study and for 3 months after last study drug administration.
• Written informed consent

You may not qualify if:

• Current treatment with any anti cancer therapy or treatment with anti cancer therapy ≤ 2 weeks prior to study treatment start unless rapidly progressing disease is measured
• Known hypersensitivity to RAD001 (everolimus) or to its excipients, or to other rapamycins (e.g. sirolimus, temsirolimus)
• Known prior history of hypersensitivity to paclitaxel.
• Paclitaxel refractory disease, which is defined as a disease progression under or within 12 weeks of last taxan treatment
• Chronic treatment with steroids (except for oral, topical or local injection) or another immunosuppressive agent
• Major surgery ≤ 2 weeks prior to starting study treatment or patients who have not recovered from such therapy
• Lack of resolution of all acute toxic effects (excluding alopecia) of prior chemotherapy, prior radiotherapy, or surgical procedure to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade \<= 1. Note: Neuropathy due to prior chemotherapy is allowed.
• Unstable CNS disease
• Requiring increasing doses of steroids to maintain stable neurological status
• Deteriorating / changing neurological status
• Known history of HIV seropositivity (HIV testing is not mandatory) or Hepatitis B or C.
• Active, bleeding diathesis or on oral anti-vitamin K medication (except low dose warfarin, as long as the INR is \<= 2.0)
• Any other severe and/or uncontrolled medical conditions

Sponsors & Collaborators

• Krankenhaus Nordwest: lead

Study Sites (1)

Krankenhaus Nordwest

Frankfurt am Main, 60488, Germany

Location

Related Publications (1)

• Lorenzen S, Knorrenschild JR, Pauligk C, Hegewisch-Becker S, Seraphin J, Thuss-Patience P, Kopp HG, Dechow T, Vogel A, Luley KB, Pink D, Stahl M, Kullmann F, Hebart H, Siveke J, Egger M, Homann N, Probst S, Goetze TO, Al-Batran SE. Phase III randomized, double-blind study of paclitaxel with and without everolimus in patients with advanced gastric or esophagogastric junction carcinoma who have progressed after therapy with a fluoropyrimidine/platinum-containing regimen (RADPAC). Int J Cancer. 2020 Nov 1;147(9):2493-2502. doi: 10.1002/ijc.33025. Epub 2020 May 7.

  PMID: 32339253 DERIVED

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

Paclitaxel; Everolimus

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Sirolimus; Macrolides; Lactones

Study Officials

• Salah-Eddin Al-Batran, MD

  Institute of Clinical Cancer Research (IKF), UCT - University Cancer Center, Frankfurt, Germany

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 23, 2010
• First Posted: November 25, 2010
• Study Start: October 1, 2011
• Primary Completion: July 1, 2017
• Study Completion: October 1, 2019
• Last Updated: January 29, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)